Boston Patients

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MEDIA COVERAGE

Boston patients

July 2013 – January 2014

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Summary

PART 1: July 2013 Wire Reuters……………………………………………………………………………………………………………… 5 Asian News International (ANI)…………..…………………………………………………………….. 6 Associated Press (AP)………………………………………………………………………………………... 7 Associated Press (AP)………………………………………………………………………………………... 8 Associated Press (AP)………………………………………………………………………………………... 9 Agence France Press (AFP)………………………………………………………………………………… 10 Bloomberg………………………………………………………………………………………………………… 12 United Press International (UPI)……………………………………………………………………….. 14 EFE……………………………………………………………………………………………………………………. 15

Broadcasting NBC-2……………………………………………………………………………………………………………….. 17 BBC…………………………………………………………………………………………………………………… 19 ABC RADIO………………………………………………………………………………………………………… 22 ABC RADIO………………………………………………………………………………………………………… 23 NBC…………………………………………………………………………………………………………………… 24 ForexTV…………………………………………………………………………………………………………….. 27 CBN…………………………………………………………………………………………………………………… 28 CBS……………………………………………………………………………………………………………………. 29 Al Jazeera………………………………………………………………………………………………………….. 31 CNN………………………………………………………………………………………………………………….. 32 NBC…………………………………………………………………………………………………………………… 35

Newspapers, magazines and blogs The New York Times…………………………………………………………………………………………. 37 The Wall Street Journal…………………………………………………………………………………….. 40 Financial Times…………………………………………………………………………………………………. 41 The Guardian…………………………………………………………………………………………………….. 43 The Times…………………………………………………………………………………………………………. 45 The Independent………………………………………………………………………………………………. 46 The Boston Globe……………………………………………………………………………………………… 49 Le Figaro………………………………………..…………………………………………………………………. 51 Forbes…………………………………………………………………………………………………………….… 52 Metro……………………………………………………………………………………………………………….. 54 Science Now……………………………………………………………………………………………………… 55 New Scientist……………………………………………………………………………………………………. 57 New Scientist……………………………………………………………………………………………………. 59 The Washington Post………………………………………………………………………………………… 61 El Mundo………………………………………………………………………………………………………….. 63 El País……………………………………………………………………………………………………………….. 64 MedPage Today………………………………………………………………………………………………… 66 Huffington Post…………………………………………………………………………………………………. 68 The Week………………………………………………………………………………………………………….. 70

2 The Scientist……………………………………………………………………………………………………… 71 Europaikos Notos……………………………………………………………………………………………… 72 The Lancet………………………………………………………………………………………………………… 73 Nature………………………………………………………………………………………………………………. 74 HIVandHEPATITIS.com………………………………………………………………………………………. 76 HIVandHEPATITIS.com………………………………………………………………………………………. 79 AIDSMAP…………………………………………………………………………………………………………… 80 Physicians Briefing…………………………………………………………………………………………….. 83

PART 2 : December 2013 / January 2014 Wire Reuters……………………………………………………………………………………………………………… 85 Bloomberg….…………………………………………………………………………………………………….. 87 United Press International (UPI)……….………………………………………………………………. 88 Europa Press…………………………………………………………………………………………………….. 90 Agenzia Italia (AGI)……………………………………………………………………………………………. 91

Broadcasting NPR…………………………………………………………………………………………………………………… 92 NBC…………………………………………………………………………………………………………………… 94 CBS……………………………………………………………………………………………………………………. 96 CNN…………………………………………………………………………………………………………………… 98

Newspapers, magazines and blogs The New York Times…………………………………………………………………………………………. 101 The Boston Globe……………………………………………………………………………………………… 103 El País……………………………………………………………………………………………………………….. 106 El País……………………………………………………………………………………………………………….. 107 El Día.……………………………………………………………………………………………………………….. 109 Libération………………………………………………………………………………………………………….. 111 La Repubblica…….……………………………………………………………………………………………… 112 Daily News……...……………………………..…………………………………………………………………. 113 HIVandHEPATITIS.com………………………………………………………………………………………. 115

Part 1:

July 2013

4 Wire

Stem-cell therapy wipes out HIV in two patients

By Ben Hirschler. LONDON Wed Jul 3, 2013 7:53am EDT

(Reuters) - Two men with HIV have been off AIDS drugs for several months after receiving stem-cell transplants for cancer that appear to have cleared the virus from their bodies, researchers reported on Wednesday.

Both patients, who were treated in Boston and had been on long-term drug therapy to control their HIV, received stem-cell transplants after developing lymphoma, a type of blood cancer.

Since the transplants, doctors have been unable to find any evidence of HIV infection, Timothy Henrich of Harvard Medical School and Brigham and Women's Hospital in Boston told an International AIDS Society conference in Kuala Lumpur.

While it is too early to say for sure that the virus has disappeared from their bodies altogether, one patient has now been off antiretroviral drug treatment for 15 weeks and the other for seven weeks.

Last July Henrich first reported that the two men had undetectable levels of HIV in their blood after their stem- cell treatment, but at that time they were still taking medicines to suppress HIV.

Using stem-cell therapy is not seen as a viable option for widespread use, since it is extremely expensive, but the latest cases could open new avenues for fighting the disease, which infects about 34 million people worldwide.

The latest cases resemble that of Timothy Ray Brown, known as "the Berlin patient", who became the first person to be cured of HIV after receiving a bone marrow transplant for leukaemia in 2007. There are, however, important differences.

While Brown's doctor used stem cells from a donor with a rare genetic mutation, known as CCR5 delta 32, which renders people virtually resistant to HIV, the two Boston patients received cells without this mutation.

"Dr. Henrich is charting new territory in HIV eradication research," Kevin Robert Frost, chief executive officer of the Foundation for AIDS Research, which funded the study, said in a statement.

Scientific advances since HIV was first discovered more than 30 years ago mean the virus is no longer a death sentence and the latest antiretroviral AIDS drugs can control the virus for decades.

But many people still do not get therapy early enough, prompting the World Health Organization to call for faster roll-out of medicines after patients test positive.

Indian generics companies are leading suppliers of HIV drugs to Africa and to many other poor countries. Major Western HIV drugmakers include Gilead Sciences, Johnson & Johnson and ViiV Healthcare, which is majority-owned by GlaxoSmithKline.

Source: http://www.reuters.com/article/2013/07/03/us-hiv-stemcells-idUSBRE9620IL20130703

7/3/13 - Hopes soar for HIV cure after 2 US men cured of virus [Asian News International]

Melbourne, July 3 (ANI): Two American men are believed to have overcome HIV, boosting hopes as they join a handful of people who are said to have been cured of the virus, to find a wider cure.

Doctors from the Brigham and Women's Hospital in Boston announced on Wednesday night that two previously HIV-positive patients no longer had detectable virus levels in their blood or tissue after having bone marrow stem-cell transplants to treat cancer between two and four years ago, the Age reported.

Remarkably, the two men - a young man and another in middle age - have also remained clear of the virus after stopping anti-retroviral therapy eight and 15 weeks ago.

When most HIV-positive people stop taking treatment, the virus becomes active again within four to eight weeks.

The Boston pair look set to join a Mississippi toddler believed to have been cured of HIV by intense treatment 30 hours after birth and Timothy Ray Brown, the "Berlin patient" famously cured of HIV six years ago after having a similar bone marrow transplant to treat cancer in Germany.

However, there is a key difference between the Berlin and Boston patients that could advance research towards a cure for HIV.

Brown received a transplant from a donor with an unusual gene mutation that resists HIV whereas the Boston patients received transplants from donors with no known resistance to the disease.

Timothy Henrich and Daniel Kuritzkes, the doctors managing the Boston patients, told an HIV conference in Malaysia that this suggested the process of stem-cell transplantation was responsible for their suspected remission.

In particular, they believe a common complication of transplantation, graft-versus-host disease, could be at play because it involves newly transplanted donor cells attacking the transplant recipient's body.

The doctors said although it was too early to say whether their patients had been cured permanently, repeated tests of large volumes of cells, plasma and tissue had found no sign of the virus. (ANI)

Source: http://www.pharmacychoice.com/News/article.cfm?Article_ID=1073362

Células madre parecen ayudar a pacientes con sida

Por EILEEN NG - 07/03/2013

KUALA LUMPUR, Malasia - Dos pacientes en Estados Unidos infectados con el virus de inmunodeficiencia humana (VIH) y que fueron sometidos a trasplante de médula ósea debido al cáncer dejaron de tomar medicinas antirretrovirales y siguen sin mostrar indicios perceptibles del virus, dijeron los investigadores el miércoles.

Los investigadores de la Universidad de Harvard insistieron que es demasiado pronto para afirmar que los hombres han sido curados, pero agregaron que es un indicio esperanzador que el virus no haya reaparecido en su sangre meses después de haber concluido su tratamiento con fármacos.

Los médicos de Brown emplearon un donante que tenía una rara mutación genética que brinda resistencia al VIH. Hasta ahora nadie ha observado resultados similares utilizando células ordinarias como las aportadas a los dos pacientes por los investigadores de la Universidad de Harvard.

Los investigadores, Timothy Henrich y Daniel Kuritzkes, del Hospital Brigham and Women de Boston, afiliado a Harvard, anunciaron el año pasado que las muestras de sangre tomadas a los hombres, ambos con cánceres de sangre, no mostraron indicio alguno del virus ocho meses después de recibir trasplantes de médula ósea para reemplazar las células cancerosas en la sangre con células sanas donadas. Los hombres seguían tomando entonces drogas anti VIH.

Desde entonces los hombres han dejado de tomar los fármacos antirretrovirales _uno hace 15 semanas y otro hace siete semanas_ y no muestran indicios del virus, dijo Henrich el miércoles en una conferencia internacional sobre el SIDA efectuada en Malasia.

"Están muy bien", dijo Henrich. "Aunque los resultados son alentadores, no indican aún que los hombres se hayan curado. Solo el tiempo lo dirá".

El virus VIH podría esconderse en otros órganos como el hígado, la vesícula o el cerebro y podría regresar meses después, advirtió.

Nuevos análisis de las células, plasma y tejido de los hombres por lo menos durante un año ayudarán a obtener una visión más clara sobre el pleno impacto del trasplante en los pacientes con VIH, dijo. Kuritzkes dijo que los pacientes volverán a recibir los fármacos si repunta su infección viral.

Un repunte indicará que otros lugares son importantes reservas del virus infeccioso y serán necesarios nuevos enfoques para medir estas reservas con el propósito de desarrollar una cura, dijo Henrich.

"Estos descubrimientos aportan claramente nueva información importante que podría alterar la creencia actual sobre el HIV y la terapia de genes", dijo en una declaración Kevin Robert Frost, director gerente de la Fundación sobre Investigaciones del sida. "Mientras que el trasplante de células madre no es una alternativa viable para las personas con VIH a gran escala debido a su costo y complejidad, estos casos nuevos podrían conducirnos a nuevos enfoques para tratar y a la postre incluso erradicar el VIH".

Source: http://www.lavozarizona.com/spanish/global/articles/global_208386.html

2 stem cell patients stop HIV drugs, no virus seen

 Eileen Ng, Associated Press  Posted July 4, 2013

KUALA LUMPUR, Malaysia (AP) — Two HIV-positive patients in the United States who underwent bone marrow transplants for cancer have stopped anti-retroviral therapy and still show no detectable sign of the HIV virus, researchers said Wednesday.

The Harvard University researchers stressed it was too early to say the men have been cured, but said it was an encouraging sign that the virus hasn't rebounded in their blood months after drug treatment ended.

The first person reported to be cured of HIV, American Timothy Ray Brown, underwent a stem cell transplant in 2007 to treat his leukemia. He was reported by his German doctors to have been cured of HIV two years later.

Brown's doctors used a donor who had a rare genetic mutation that provides resistance against HIV. So far, no one has observed similar results using ordinary donor cells such as those given to the two patients by the Harvard University researchers.

The researchers, Timothy Henrich and Daniel Kuritzkes of the Harvard-affiliated Brigham and Women's Hospital in Boston, announced last year that blood samples taken from the men — who both had blood cancers — showed no traces of the HIV virus eight months after they received bone marrow transplants to replace cancerous blood cells with healthy donor cells. The men were still on anti-HIV drugs at the time.

The men have both since stopped anti-retroviral therapy — one 15 weeks ago and the other seven weeks ago — and show no signs of the virus, Henrich told an international AIDS conference in Malaysia on Wednesday.

"They are doing very well," Henrich said. "While these results are exciting, they do not yet indicate that the men have been cured. Only time will tell."

The HIV virus may be hiding in other organs such as the liver, spleen or brain and could return months later, he warned.

Further testing of the men's cells, plasma and tissue for at least a year will help give a clearer picture on the full impact of the transplant on HIV persistence, he said.

Kuritzkes said the patients will be put back on the drugs if there is a viral rebound.

A rebound will show that other sites are important reservoirs of infectious virus and new approaches to measuring these reservoirs will be needed in developing a cure, Henrich said.

"These findings clearly provide important new information that might well alter the current thinking about HIV and gene therapy," Kevin Robert Frost, chief executive of The Foundation of AIDS Research, said in a statement. "While stem cell transplantation is not a viable option for people with HIV on a broad scale because of its costs and complexity, these new cases could lead us to new approaches to treating, and ultimately even eradicating, HIV."

Source: http://www.commercialappeal.com/news/2013/jul/04/2-stem-cell-patients-stop-hiv-drugs-no-virus-seen

Enfermos de sida mejoran tras ser tratados con células madre Dos pacientes con cáncer de sangre no muestran indicios del virus meses después de la operación Sanidad | 04/07/2013

Detalle de pruebas para la detección del sida (VIH). Roberto Escobar | EFE

Kuala Lumpur (Malasia). (AP).- Dos pacientes en Estados Unidos infectados con el virus de inmunodeficiencia humana (VIH) y que fueron sometidos a trasplante de médula ósea debido al cáncer dejaron de tomar medicinas antirretrovirales y siguen sin mostrar indicios perceptibles del virus, según aseguraron investigadores de la Universidad de Harvard el pasado miércoles. Tras insistir en que aún es demasiado pronto para afirmar que los hombres han sido curados, agregaron que es un indicio esperanzador que el virus no haya reaparecido en su sangre meses después de haber concluido su tratamiento con fármacos.

La primera persona que al parecer fue curada del VIH fue el estadounidense Timothy Ray Brown, que se sometió a un trasplante de células madre en 2007 para tratar su leucemia. Sus médicos alemanes dijeron que se había curado del VIH dos años después. Los médicos de Brown emplearon un donante que tenía una rara mutación genética que brinda resistencia al VIH. Pero hasta ahora nadie ha observado resultados similares utilizando células ordinarias como las aportadas a los dos pacientes por los investigadores de la Universidad de Harvard.

Los investigadores, Timothy Henrich y Daniel Kuritzkes, del Hospital Brigham and Women de Boston (perteneciente a Harvard), anunciaron el año pasado que las muestras de sangre tomadas a los hombres, ambos con cánceres de sangre, no mostraron indicio alguno del virus ocho meses después de recibir trasplantes de médula ósea para reemplazar las células cancerosas en la sangre con células sanas donadas. Los hombres seguían tomando entonces drogas anti VIH. Desde entonces los hombres han dejado de tomar los fármacos antirretrovirales (uno hace 15 semanas y otro hace siete semanas) y no muestran indicios del virus, dijo Henrich el miércoles en una conferencia internacional sobre el sida efectuada en Malasia.

"Están muy bien", dijo Henrich. "Aunque los resultados son alentadores, no indican aún que los hombres se hayan curado. Solo el tiempo lo dirá". El virus VIH podría esconderse en otros órganos como el hígado, la vesícula o el cerebro y podría regresar meses después, advirtió. Nuevos análisis de las células, plasma y tejido de los hombres por lo menos durante un año ayudarán a obtener una visión más clara sobre el pleno impacto del trasplante en los pacientes con VIH, afirmó.

Kuritzkes señaló asimismo que los pacientes volverán a recibir los fármacos si repunta su infección viral. Un repunte indicará que otros lugares son importantes reservas del virus infeccioso y serán necesarios nuevos enfoques para medir estas reservas con el propósito de desarrollar una cura, dijo Henrich. "Estos descubrimientos aportan claramente nueva información importante que podría alterar la creencia actual sobre el HIV y la terapia de genes", dijo en una declaración Kevin Robert Frost, director gerente de la Fundación sobre Investigaciones del sida. "Mientras que el trasplante de células madre no es una alternativa viable para las personas con VIH a gran escala debido a su costo y complejidad, estos casos nuevos podrían conducirnos a nuevos enfoques para tratar y a la postre incluso erradicar el VIH".

Source: http://www.lavanguardia.com/salud/20130704/54377226171/celulasmadre-sida-vih-antirretroviales- harvard.html#ixzz2riU1mXxH

Agence France-Presse July 3, 2013 New research boosts search for cure, AIDS meeting told

Fresh data from several small trials presented at an AIDS conference on Wednesday provides encouraging news in the quest for a cure for HIV, scientists said.

Giving an update in an eagerly-followed trial, researchers said an HIV-positive infant in Mississippi who was put on a course of antiretroviral drugs within a few days of birth had remained free of the AIDS virus 15 months after treatment was stopped.

In Boston, two HIV-positive men who were given bone-marrow transplants for cancer also had no detectable virus 15 weeks and seven weeks respectively after stopping AIDS drugs, a separate team reported.

Both research projects are at an early stage and should not be taken as a sign that a cure for the human immunodeficiency virus (HIV) is around the corner, researchers cautioned at a world forum of AIDS scientists in Kuala Lumpur.

Even so, they said it strengthens the motivation for pursuing the once-unthinkable goal of eradicating HIV or repressing it without daily drugs -- a condition referred to as a "functional cure" or "functional remission".

"I don't actually want to use the cure word in this situation," said Timothy Henrich, from the Brigham and Women's Hospital in Boston, Massachusetts, of the bone-marrow study he is co-leading.

"But what I can say is that if these patients are able to stay without detectable HIV for at least a year, maybe a year and a half, after we stop treatment, then the chances of the virus coming back are very small," he told an AFP correspondent in Paris.

Introduced in 1996, the famous cocktail of antiretroviral drugs is a lifeline to millions with HIV.

But if the drugs are stopped, the virus rebounds from "reservoirs" among old cells in the blood stream and body tissue. It then renews its attack on CD4 cells, part of the immune system's heavy weaponry.

Deborah Persaud, heading the so-called Mississippi Child investigation, said early treatment of newborns appears to offer the best hope of attacking the virus before it gets established in these reservoirs.

"Therapy in the first few days of life really curtailed the reservoir formation to the point that (it) was not established in this child and allowed treatment cessation without having the virus rebound," Persaud, an associate professor of pediatrics at Johns Hopkins Children's Center in Baltimore, Maryland, said by phone.

An estimated 34 million people are infected with HIV worldwide, and about 1.8 million die each year.

The virus was first identified in 1981, and until the advent of antiretrovirals was essentially a death sentence, progressively destroying the immune system until the patient succumbed to pneumonia or another opportunistic disease.

Three years ago, Nobel-winning French researcher Francoise Barre-Sinoussi launched a campaign for a cure -- a hope bolstered by the case of a Berlin man whose HIV-count dropped to undetectable levels after a bone-marrow transplant for leukaemia.

In his case, the transplanted cells had a genetic variant, called CCR5 delta-32, which thwarts HIV's attempts to latch on to the cell's surface and then penetrate it.

10 The two Boston patients did not have this mutation in their transplants.

But they were kept on antiretrovirals until the donor cells were fully established in their bodies, and this may have helped, suggested Henrich.

In two other studies presented at the International AIDS Society (IAS) conference, French researchers said patients who began treatment as soon as possible after diagnosis had the best chance of shrinking the viral reservoir and reviving their immune system.

This backs new treatment guidelines published by the UN World Health Organization and strengthens hopes for a drug-free life for HIV patients, the French National Agency for Research on AIDS (ANRS) said.

"Given the large decrease in reservoirs in these two studies, it is possible that functional remission, i.e. prolonged control of the infection without treatment, may in time be achieved in patients treated early," ANRS chief Jean- Francois Delfraissy said.

The four-day IAS meeting concluding on Wednesday is held every two years. ri/mlr/jms/mtp

Source: http://www.globalpost.com/dispatch/news/afp/130703/new-research-boosts-search-cure-aids-meeting- told

Stem Cell Transplants Clear HIV in Two Patients in Study By Simeon Bennett Jul 3, 2013

Photographer: Noah Berger/Bloomberg

Two cancer patients in Boston who were also infected with HIV have no trace of the virus after receiving stem- cell transplants, suggesting they may have been cured of the AIDS-causing infection.

The two patients, treated at Brigham and Women’s Hospital, stopped HIV treatment after the transplants, which in other patients has opened the door for the virus to come roaring back. In one patient there was no sign of the virus 15 weeks after stopping treatment, while the other has gone seven weeks without HIV rebounding, according to results presented today at the International AIDS Society’s meeting in Kuala Lumpur.

The researchers led by Timothy Henrich of Harvard Medical School and Brigham and Women’s Hospital said it’s too early to conclude the two men have been cured and the virus may be lingering in their brains or gut. Still, their cases are similar to that of Timothy Brown, the so-called Berlin patient, who was the first person to be cured of HIV after getting a bone marrow transplant for leukemia in 2007.

“While stem-cell transplantation is not a viable option for people with HIV on a broad scale because of its costs and complexity, these new cases could lead us to new approaches to treating, and ultimately even eradicating, HIV,” Kevin Robert Frost, the chief executive officer of amfAR, The Foundation for AIDS Research, which funded the study, said in a statement.

Gene Mutation

There was one main difference between Brown and the two Boston men: the cells he received contained a rare genetic mutation called CCR5 that made him resistant to HIV infection. The donors in the new cases lacked that mutation, and the Boston patients didn’t undergo the intensive chemotherapy Brown did.

Scientists had believed the CCR5 mutation was key to Brown being cured. They’ll be searching through the new results for clues to whether other genes may hold promise against HIV, Rowena Johnston, amfAR’s director of research, said in an e-mail.

12 “This stuff is really very exciting scientifically, and it really captures the imagination of the patients,” said Paul E. Sax, a professor of medicine at Harvard Medical School and a clinician at Brigham and Women’s. “All of us get asked by our patients about these cases, even to the point of people actually requesting bone marrow transplants.”

Drug Cocktails

While AIDS drugs such as Gilead Sciences Inc. (GILD)’s Atripla reduce HIV to undetectable levels in the body, making it a chronic disease, they don’t completely clear it. The virus hides in certain immune cells, where it switches off the normal process of replication. That enables HIV to avoid detection by the medicines, which are designed to block steps in its reproduction.

Studies have shown that when patients who have the virus under control stop treatment, latent HIV reactivates and comes roaring back, forcing victims to resume daily pill therapy.

Doctors in March said they had cured an infant born with HIV for the first time by treating her with AIDS drugs about 30 hours after she was born at a rural Mississippi hospital. At 18 months the mother took the child off medication, and when the virus had not returned 10 months later, she was deemed “functionally cured.”

Source: http://www.bloomberg.com/news/2013-07-03/stem-cell-transplants-clear-hiv-in-two-patients-in- study.html

Two men HIV free after bone marrow transplant July 3, 2013

Men HIV free after bone marrow transplant and ending anti-retrovirals. Rev. Al Sharpton delivers remarks during the Keep the Promise on HIV/AIDS rally. UPI/Kevin Dietsch

KUALA LUMPUR, Indonesia, July 3 (UPI) -- Two men with longstanding HIV infections who had bone marrow transplants no longer need anti-retroviral therapy, U.S. researchers say.

Dr. Timothy Henrich and Dr. Daniel Kuritzkes, physician-researchers in the Division of Infectious Diseases at Brigham and Women's Hospital in Boston said one patient stopped anti-retroviral therapy 15 weeks ago, the other stopped seven weeks ago.

Last summer, Henrich and Kuritzkes announced the virus was easily detected in blood lymphocytes of both men prior to their transplants and became undetectable by eight months post-transplant. However, at the time, the men remained on anti-retroviral therapy.

Since coming off anti-retroviral therapy this spring, the men continue to have no detectable HIV DNA or RNA in their blood, the researchers said.

"While these results are exciting, they do not yet indicate that the men have been cured," Henrich said in a statement. "Long-term follow up of at least one year will be required to understand the full impact of a bone marrow transplant on HIV persistence."

The study demonstrated at least a 1,000-10,000 fold reduction in the size of the HIV reservoir in the peripheral blood of these two patients, but the virus could still be present in other tissues such as the brain or gastrointestinal track, Henrich said.

"If virus does return, it would suggest that these other sites are an important reservoir of infectious virus and new approaches to measuring the reservoir at relevant sites will be needed to guide the development of HIV curative strategies," Henrich said.

The findings were presented Wednesday at the International AIDS Society Conference in Kuala Lumpur, Malaysia.

Source: http://www.upi.com/Health_News/2013/07/03/Two-men-HIV-free-after-bone-marrow-transplant/UPI- 82581372872451/#ixzz2rQiZj1jQ

Dos hombres con VIH podrían haberse curado tras un trasplante de médula El estudio analizó la evolución de dos pacientes infectados de sida que se sometieron a un trasplante tras haberles sido detectado un cáncer Sanidad | 27/07/2012

Una imagen del virus de la inmunodeficiencia humana (VIH) tomada con un microscopio Science

Washington. (EFE).- Dos personas podrían haberse curado del VIH después de haber sido sometidas a un trasplante de médula ósea para tratar un cáncer, según un estudio difundido hoy en la XIX Conferencia Internacional sobre el Sida en Washington.

El estudio, liderado por el doctor Daniel Kuritzkes del Hospital de Mujeres de Brigham en Boston (Massachusetts), analizó la evolución de dos pacientes infectados de sida que se sometieron a un trasplante de médula ósea tras haberles sido detectado un cáncer. Los dos hombres, infectados durante años, se habían sometido a la terapia antirretroviral que suprimió por completo la reproducción del VIH, aunque tenían el virus latente antes del trasplante, según el estudio.

Antes de someterse al trasplante, ambos pacientes recibieron una forma más leve de la quimioterapia, lo que les permitió continuar con sus medicamentos para el VIH durante todo el proceso del trasplante. Según el estudio, los médicos detectaron el VIH inmediatamente después del trasplante, pero, con el tiempo, las células trasplantadas sustituyeron a los linfocitos propios de los pacientes, y la cantidad de VIH en el ADN de sus cédulas disminuyó hasta el punto de que se hizo indetectable. Uno de los pacientes fue sometido a seguimiento médico durante casi dos años después del trasplante y el otro durante tres años y medio, y "no hay rastro del virus", según informó la organización en un comunicado. Ambos casos recuerdan al de Thimothy Brown, conocido como "el paciente de Berlín", que dejó de tomar los antirretrovirales para someterse a un complicado tratamiento con células de un donante para combatir una leucemia mieloidea.

Posteriormente, su organismo no dio nuevos signos de VIH. No obstante, los expertos señalan que, a diferencia de Brown que recibió células madre del tipo denominado CD4 que no poseen el receptor CCR5 -necesario para que el virus se propague por el organismo-, los dos pacientes del estudio recibieron células comunes. "Creemos que la administración continua de una terapia antirretroviral, que protege a las células -provenientes- del donante de infectarse del VIH mientras eliminan y sustituyen a las células de los pacientes, es efectiva para eliminar el virus de los linfocitos de la sangre de los pacientes", indicaron los expertos.

Aún así, los médicos se mantienen cautelosos y, a la pregunta de si podrían considerar que los pacientes están curados, Kuritzkes señaló que "estamos siendo muy cuidadosos en no hacer eso",

15 según declaraciones recogidas por el canal de televisión MSNBC. De momento, los dos hombres están tomando fármacos antirretrovirales hasta que se les puedan ir retirando bajo condiciones experimentales. "No estamos diciendo: Son como el 'paciente de Berlín'", señaló Kuritzkes.

Los dos pacientes no han sido identificados por razones de privacidad pero, según MSNBC, uno de ellos está en la cincuentena y fue infectado en la década de 1980, mientras que el otro tiene 20 años y fue infectado al nacer. "Las palabras no pueden comenzar a expresar mi alegría de que otros dos hombres puedan haber sido curados de VIH", señaló Brown, hasta ahora el único paciente considerado curado de VIH, y que acaba de lanzar su propia fundación para buscar una cura al sida. "Esto refuerza mi determinación y la convicción de que debemos cumplir con la misión central de mi fundación de invertir en terapias de vanguardia y tratamientos para avanzar en la investigación de la cura del sida", dijo en un comunicado. Brown expresó su deseo de que "todo el mundo se cure" y espera que estos nuevos casos "representen el comienzo del fin de esta plaga".

Source: http://www.lavanguardia.com/salud/20120727/54330389097/hombres-vih-curado-trasplante- medula.html#ixzz2riSzTmHd

16 Broadcasting

No trace of HIV after stem-cell transplants, researchers say Updated: July 3, 2013

By Dennis Thompson HealthDay Reporter

WEDNESDAY, July 2 (HealthDay News) -- Two HIV-positive patients show no trace of virus after receiving chemotherapy and stem-cell transplants as treatment for lymphoma, according to new research.

These patients have become the second and third known cases of a "sterilizing cure," in which medical treatment removes all traces of HIV -- the virus that causes AIDS -- from the body. They have remained virus-free even though doctors months ago took them off their HIV-targeted medications.

"We have been unable to detect virus in either the blood cells or the plasma of these patients," said lead researcher Dr. Timothy Henrich, of Harvard Medical School and Brigham and Women's Hospital in Boston. "We also biopsied gut tissue from one of our patients, and we were unable to detect HIV in the cells of the gut. Essentially, we do not have any evidence of viral rebound."

The findings are scheduled for presentation Wednesday at the International AIDS Society Conference in Kuala Lumpur, Malaysia.

The patients had been receiving long-term antiretroviral therapy for HIV when they developed lymphoma, a type of blood cancer involving white blood cells, Henrich said.

Both underwent chemotherapy followed by bone marrow transplants to cure their lymphoma. Afterward, Henrich could not detect any HIV infection in their bodies.

Henrich presented preliminary findings on the research at the International AIDS Conference last July. Since then, he and his research team withdrew the patients' antiretroviral therapy to see how completely the cancer treatment had rid them of HIV. One patient has been off treatment with no detectable virus for about 15 weeks, and the second patient for seven weeks.

Henrich warned that it is too soon to declare the patients completely cured of HIV. "Although we cannot detect HIV, it's possible it's there but in extremely low amounts," he said. "We're going to watch and wait, and see where it goes with these patients."

Unfortunately, this type of cure is not something that can be put into widespread practice for all people infected with HIV. "Transplantation is not a scalable, affordable or even safe treatment for HIV patients," Henrich said.

The so-called "Berlin patient," Timothy Brown, is the first documented case of a sterilizing cure for HIV. An American man living in Germany who received a bone marrow transplant for leukemia, Brown has remained HIV-free even after discontinuing his antiretroviral drug therapy. The transplanted bone marrow cells came from a donor who had a rare genetic mutation that increases immunity against the most common form of HIV, and researchers believe that helped protect Brown from re-infection.

In Mississippi, a baby born with HIV nearly three years ago is the first case of a "functional cure," in which early treatment eradicates the virus. Immediate treatment with antiretroviral medications rid the child of all traces of HIV within the first month of life, and she has remained virus-free even after discontinuing drug therapy at 18 months of age.

17 Henrich's findings are significant because his two patients did not receive bone marrow cells with the genetic mutation that helped Brown. They also did not receive the intensive chemotherapy or total body irradiation that preceded Brown's stem-cell transplant.

Instead, their stem-cell transplants appear to have been protected by the patients' ongoing antiretroviral therapy, which continued as they received cancer treatment.

"In bone marrow transplants, the donor cells actually eliminate and replace the host patient's blood cells," Henrich said. "Antiretroviral therapy allowed the donor cells to replace the host cells without becoming infected."

By comparing Brown with the two new patients, researchers hope to better understand the immune responses that have protected all three, said Rowena Johnston, vice president and director of research for amfAR, the Foundation for AIDS Research, which is funding Henrich's research.

"It was quite unclear at the time how that cure came about," Johnston said of the Brown case. "One way these Henrich findings are significant is that they allowed us to tease apart those factors that may have been key to curing Timothy Brown."

Together, the three patients can tell researchers a lot about the barriers to a cure and how they might be overcome, Johnston continued.

Perhaps some day the treatment that helped these patients will be available to everyone with HIV, she added.

"We currently imagine that curing people on a large scale through stem-cell transplantation would pose many daunting challenges, but gene therapy researchers are working on ways this might one day be possible," Johnston said.

Findings presented at meetings should be considered preliminary until published in a peer-reviewed medical journal.

More information

For more information on HIV cures under investigation, visit amfAR, the Foundation for AIDS Research.

Source: http://www.nbc-2.com/story/22752300/no-trace-of-hiv-after-stem-cell-transplants-researchers-say

Bone marrow 'frees men of HIV drugs' By James Gallagher Health and science reporter, BBC News 3 July 2013

Two patients have been taken off their HIV drugs after bone-marrow transplants seemed to clear the virus from their bodies, doctors report.

One of the patients has spent nearly four months without taking medication with no sign of the virus returning.

The team at Brigham and Women's Hospital, in the US, caution that it is far too soon to talk about a cure as the virus could return at any point.

The findings were presented at the International Aids Society Conference.

It is difficult to get rid of an HIV infection because it hides inside human DNA, forming untouchable "reservoirs" in body.

Anti-retroviral drugs keep the virus in check within the bloodstream - but when the drugs stop, the virus comes back.

HIV gone?

 The two men, who have not been identified, had lived with HIV for about 30 years.  They both developed a cancer, lymphoma, which required a bone-marrow transplant.  Bone marrow is where new blood cells are made and it is thought to be a major reservoir for HIV.  After the transplant, there was no detectable HIV in the blood for two years in one patient and four in the other.  The pair came off their anti-retroviral drugs earlier this year.  One has gone 15 weeks, and the other seven, since stopping treatment, and no signs of the virus have been detected so far.

Dr Timothy Henrich told the BBC the results were exciting. But he added: "We have not demonstrated cure, we're going to need longer follow-up.

"What we can say is if the virus does stay away for a year or even two years after we stopped the treatment, that the chances of the virus rebounding are going to be extremely low.

19 "It's much too early at this point to use the C-word [cure]."

It is thought that the transplanted bone marrow was initially protected from infection by the course of antiretrovirals. Meanwhile the transplant also attacked the remaining bone marrow, which was harbouring the virus.

However Dr Henrich cautioned that the virus could be still be hiding inside brain tissue or the gastrointestinal track.

"If [the] virus does return, it would suggest that these other sites are an important reservoir of infectious virus and new approaches to measuring the reservoir at relevant sites will be needed to guide the development of HIV curative strategies," he said.

Berlin patient

Timothy Brown, also known as the "Berlin patient" is thought to be the first person cured of Aids. He had a bone marrow transplant from a rare donor who was resistant to HIV.

The two US cases both received bone marrow from normal donors.

There was also a report of an HIV cure in a baby born in Mississippi, US. She was treated with anti-retroviral drugs at birth so it is thought the virus was cleared from the body before reservoirs were established.

Dr Michael Brady, the medical director of the Terrence Higgins Trust, said: "It is too early to know whether HIV has been eradicated from these men's bodies or whether it might return.

Doctors say it is far too soon to talk about a cure for HIV, as James Gallagher reports

"However, the case suggests that what happened to Timothy Brown, the Berlin Patient was perhaps not a one- off.

"A bone marrow transplant is a complex and expensive procedure, which comes with significant risks.

"For most people with HIV, it would be more dangerous to undergo a transplant than to continue managing the virus with daily medication.

"So while this is by no means a workable cure, it does give researchers another signpost in the direction of one."

The head of the Foundation for AIDS Research, Kevin Frost, said: "These findings clearly provide important new information that might well alter the current thinking about HIV and gene therapy.

20 "While stem-cell transplantation is not a viable option for people with HIV on a broad scale because of its costs and complexity, these new cases could lead us to new approaches to treating, and ultimately even eradicating, HIV."

Analysis

 It is far too early to call this a cure for HIV. And even if it was a cure, it wouldn't be a very good one.  It is very expensive and often leads to "graft-v-host" disease. There is a 15-20% mortality rate within the first few years after the transplant.  This occurs when new immune cells produced by the graft treat the rest of the body as foreign and attack it.  The two patients in this study have replaced their regimen of anti-retroviral drugs, with those to suppress the immune system.  The procedure was carried out in these patients only because they had cancer that needed to be treated.  The real value of this research for the majority of people with HIV will come from a deeper understanding of the virus and HIV reservoirs.

Source: http://www.bbc.co.uk/news/health-23132561

HIV Undetectable in Two Patients After Bone Marrow Transplant Wednesday, July 3, 2013

Ingram Publishing/Thinkstock(KUALA LUMPUR, Malaysia) -- Two HIV-positive patients who underwent bone marrow transplants have shown no sign of their HIV infection despite being off HIV drugs for months.

Harvard Medical School researcher Dr. Timothy Henrich announced Wednesday that he has been unable to detect HIV in two of his patients who purposefully went off antiretroviral therapy for 15 and seven weeks, respectively. Although it’s not clear whether their HIV will return, the findings may represent another step toward a cure.

“Both patients have been very involved in the research,” Henrich said at the International AIDS Society conference in Kuala Lampur. “They’ve been very interested in what we are doing. And they’ve been very excited to participate in the studies that are ongoing.”

The two patients had been on long-term antiretroviral therapy, which suppresses HIV and stops its progression into full-blown AIDS, but they both developed lymphoma several years ago. To treat the cancer, Henrich treated these men with chemotherapy and a bone marrow transplant, but they continued antiretroviral therapy during and after transplant.

This year, Henrich conducted a clinical study in which he instructed the patients to stop taking antiretrovirals to see what would happen. So far, the virus has not rebounded, as it normally would have without continued antiretroviral therapy.

“It’s possible the virus could come back next week. It’s possible the virus could come back months from now, and it’s even possible that it could take one or two years for this virus to return to these patients,” Henrich said. “We still do not know the full impact of the findings that we have.”

Although more research is needed, Henrich said it’s possible the patients were able to suppress the HIV without drugs because of a bone marrow transplant complication called “graft-versus-host.” Although this complication usually has a negative connotation, it could mean that the donor stem cells in the bone marrow attacked the HIV patients’ remaining HIV-positive cells and replaced them with healthy ones.

Perhaps the most famous HIV-positive patient to receive a bone marrow transplant is known as “the Berlin patient,” a man who stopped taking antiretrovirals the day of his transplant in 2006 and says he hasn’t needed them since. This man, however, accepted a bone marrow transplant from a donor with a mutation called CCR5, which makes patients immune to HIV.

Henrich said his patients received bone marrow from donors who did not have this mutation, meaning their cells were susceptible to HIV infection.

Earlier this year, doctors announced that they’d “fundamentally cured” a rural Mississippi baby by introducing high doses of antiretrovirals just hours after the little girl was born to an HIV-positive mother. Less than two weeks later, French researchers claimed they had 14 HIV-positive patients who’d experienced remission after stopping antiretroviral therapy because it was “fashionable at the time.”

Source: http://abcnewsradioonline.com/health-news/hiv-undetectable-in-two-patients-after-bone-marrow- transplan.html

Researchers question practicalities of HIV 'cure'

Download audio: http://mpegmedia.abc.net.au/rn/podcast/2013/07/bst_20130708_0819.mp3

Monday 8 July 2013

Last week RN Breakfast discussed reports that the world may be closer to a cure for HIV-AIDS. The news came after the HIV virus was no longer detectable in two cases in the US, where the patients underwent bone marrow stem cell transplants. Many researchers however, are questioning whether these radical treatments are practical, and whether they distract from the search for more effective HIV drug treatments.

Source: http://www.abc.net.au/radionational/programs/breakfast/researchers-question-practicalities-of-hiv- cure/4805206

Treated for cancer, two men now appear free of HIV Maggie Fox NBC News July 3, 2013

Steve Forrest / International AIDS Society Dr. Daniel Kuritzkes of Brigham and Women’s Hospital, speaking at an AIDS research conference in Kuala Lumpur, Malaysia, where his team is announcing details about two cancer patients whose treatment appears to have eradicated their HIV infections.

Two men who had grueling bone marrow treatments for cancer are enjoying a happy side effect: They appear free of the AIDS virus, researchers reported on Wednesday.

The doctors are not quite ready to call it a cure, but they say the men have stopped taking HIV drugs and have remained free of the virus for almost four months in one case and almost two months in another.

“While these results are exciting, they do not yet indicate that the men have been cured,” says Dr. Timothy Henrich of Brigham and Women’s Hospital and Harvard Medical School in Boston.

The cases of the two men, who don’t want their names released, were first reported at an international AIDS conference in Washington last July. Henrich, Dr.Daniel Kuritzkes and colleagues had actively looked for HIV patients with leukemia or lymphoma who had received bone marrow stem cell transplants.

They wanted to replicate the case of Timothy Brown, also known as the "Berlin patient," who was treated for leukemia with a bone marrow transplant that happened to come from a donor with a genetic mutation that makes immune cells resist HIV infection. The transplant replaced his own infected cells with healthy, AIDS-resistant cells, and he remains free of the virus more than five years later.

They found three patients who had remained on HIV regimens while undergoing bone marrow transplants, which are designed to destroy the cancer and replace diseased blood and immune systems with healthy ones from donors.

The patients' own bone marrow is destroyed, usually with chemotherapy or radiation, and replaced with a tissue- matched transplant from a donor.

Henrich said at the time that the AIDS cocktails likely protected the new transplanted bone marrow from infection.

24 One patient is HIV-free nearly three years later, and the other more than four years later. Each made the choice to discontinue his AIDS drugs a few weeks ago.

Now there is still no evidence the virus is anywhere in their bodies, Henrich says. He’ll report his findings to a meeting of the International AIDS Society in Malaysia.

“Up to week 14 for both patients, we continue to be unable to detect (HIV) DNA in their cells or virus in their blood,” Henrich says.

“We looked very deeply this time -- much more deeply than last time.” They looked in the immune cells that HIV attacks, especially the CD4 and CD8 T-cells. They also took samples of rectal tissue from one patient to make sure no virus was hiding there. The one place they didn’t look was in the brain. “We didn’t feel the risk of that was justified,” Henrich says.

The patients will get weekly blood tests for at least a year or more, says Henrich. “We don’t even know where some of the HIV might be hiding,” he says.

The case raises a big question that some AIDS specialists never dreamed they would be asking: When do you declare a cure?

"There never is an 'aha' moment when you suddenly can declare a cure," says Kevin Robert Frost, CEO of thee Foundation for AIDS Research (amFAR), which helped pay for the study. "it is impossible to prove the absence of something."

The human immunodeficiency virus that causes AIDS is transmitted sexually, in blood, on infected needles, at birth and in breast milk.

HIV drugs called antiretroviral therapy can keep the virus suppressed to such low levels that patients are healthy and their immune systems are not damaged. People taking the drugs are also less likely to infect someone else, and studies show that uninfected people who take them are much less likely to become infected.

So doctors believe the drugs can stop the virus from infecting cells and, perhaps, from hiding out in the body. But people who are infected and who stop taking their drugs almost always have the virus come back at some point, so it does lurk in what are known as reservoirs.

Henrich says doctors have been debating when and if to declare the patients cured. Timothy Brown, the Berlin patient, says he is. “What is the definition of a cure? “ Henrich asked. “Even with the Berlin patient, who is five years out, it could come back, although the chances are very small.”

A third patient who also seemed HIV-free died when his lymphoma returned, Henrich said. It’s clear this isn’t a treatment for the average HIV patient, but it does show it may be possible to eradicate the virus. It also suggests that HIV patients who do get leukemia or lymphoma should stay on their HIV drugs during treatment.

Then there is the widely reported case of a baby in Mississippi whose HIV infection disappeared after unusually early and aggressive drug treatment. “She’s doing quite well,” says Dr. Hannah Gay of the University of Mississippi Medical Center, who treated the child.

The child, who lives in rural Mississippi, is now 3 years old and still has no evidence of active HIV infection. She was born to a mother who didn’t know until right before she gave birth that she had HIV, and when the child was diagnosed with the virus, Dr. Gay decided on an unusual course of aggressive treatment.

Gay's colleagues reported at another AIDS meeting in March that the treatment appears to have eradicated what’s known as “replication-capable” virus, although some tests do show evidence of HIV in the child’s body.

“We still don’t know exactly when to declare a cure and that's the case even with the Berlin patient,” Gay told NBC News.

25 “Our baby is doing great. It is our intention to keep following her closely. We know that … there is the possibility she has some cells hidden there that are infected with replication-competent virus that somewhere down the line could come back out. We are aware that is a possibility,” Gay added.

Frost says it may change the direction of research. Timothy Brown was given transplants of bone marrow cells from a patient with a mutation in a gene called CCR5, which makes people resistant to HIV infection. But the latest two patients got ordinary cells.

"Most people thought that was a critical component of what had been achieved in the Berlin patient. I think this changes the game," Frost told NBC News.

Henrich says it is possible that transplanted immune system cells destroyed any remaining HIV-infected cells as part of their normal and expected scavenging of alien cells -- which would include any of the patients' own immune cells left after the pre-transplant destruction.

Frost said he had not heard of any other patient going as long at 15 weeks without HIV drugs without the virus coming back. But he is nonetheless cautious. "My sense is we going to be at least a year out before anybody is going to be prepared to make claims about what these cases really mean," he says. "You want to be at least a year out before you would consider declaring a victory."

“Whatever the outcome, we will have learned more about what it will take to cure HIV," added amfAR research director Dr. Rowena Johnston.

Source: http://www.nbcnews.com/health/treated-cancer-two-men-now-appear-free-hiv-6C10507557

Big Breakthrough in HIV Treatment, Stem Cell Therapy

Lisa Judd | July 3 2013

Two men with HIV have been off their medication after a stem-cell transplant normally given to cancer patients. The two patients were being treated in Boston, Massachusetts; both had been on long-term anti-viral medication to control their HIV and had developed lymphoma (a blood cancer). They received a stem-cell transplant for the lymphoma. Since then they have not been able to find any evidence of HIV infection. It is still too early to tell if they will remain free of the HIV infection.

Timothy Henrich of Harvard Medical School and Brigham & Women’s Hospital in Boston has been following the men. He reported last July that they were not able to confirm any HIV blood levels after their stem-cell treatment, but they were still taking their anti-viral medications. Presently one of them has been off their medication for 15 weeks and the other for 7 weeks.

Finding out you are HIV positive used to be a death sentence, but thanks to ongoing scientific advances, patients live for decades with the disease under control. Is stem-cell transplant a cure for HIV and AIDS world-wide, probably not. It is an expensive procedure, but will lead to further studies on how to fight and eliminate the disease that infects over 34 million people worldwide.

The latest cases resemble that of Timothy Ray Brown, known as "the Berlin patient", who became the first person to be cured of HIV after receiving a bone marrow transplant for leukemia in 2007. There are, however, important differences.

"Dr. Henrich is charting new territory in HIV eradication research," Kevin Robert Frost, chief executive officer of the Foundation for AIDS Research, which funded the study, said in a statement.

Source: http://www.forextv.com/forex-news-story/big-breakthrough-in-hiv-treatment-stem-cell-therapy

Bone Marrow Recipients Now Appear HIV Free CBNNews.com Wednesday, July 03, 2013

Two HIV-positive patients who received bone marrow transplants for cancer now show no signs of the deadly virus.

Researchers Timothy Henrich and Daniel Kuritzkes, of Brigham and Women's Hospital and Harvard Medical School in Boston, announced last year that eight months after receiving healthy donor cells, the virus had not re-appeared in the patients' blood.

However, the patients were still taking anti-retroviral drugs at the time.

On Wednesday, Henrich and Kuritzkes said that the patients still appear to be HIV free even though they've stopped taking the drugs. They made the announced an international AIDS conference in Malaysia.

"While these results are exciting, they do not yet indicate that the men have been cured," Henrich said.

Source: http://www.cbn.com/cbnnews/healthscience/2013/July/Bone-Marrow-Recipients-Now-Appear-HIV- Free1

By Michelle Castillo CBS News July 3, 2013, 3: 52 PM Two men "cured" of HIV no longer taking treatments

Doctors are reporting that two previously HIV-positive men who received stem cell transplants to treat their cancers no longer have any traces of the virus even after stopping treatment.

Dr. Timothy Henrich, an associate physician at Brigham and Women's Hospital in Boston, said at the International AIDS Society conference in Kuala Lumpur that the men are no longer taking AIDS drugs. Currently, the first patient has been off treatments for 15 weeks and the other has been off for seven weeks, Reuters reported.

The patients received the stem-cell transplants after they had been diagnosed with the blood cancer lymphoma. In July 2012, Henrich had reported that the two men had undetectable levels of HIV in their blood, but they were still taking medication at the time.

Currently 33.4 million people are living with HIV (human immunodeficiency virus) or AIDS (acquired immune deficiency syndrome), according U.S. government statistics.

In the U.S. alone, 1.7 million people have been infected with HIV by the end of 2008, the most recent year where statistics are available. Every 9.5 minutes, someone is infected with HIV. Currently, one out of five people living with HIV are unaware that they are infected.

Man "cured" of AIDS: Timothy Ray Brown

These two men aren't the first to be "cured" of HIV. Timothy Ray Brown, a man who previously had HIV and leukemia, received a stem cell transplant from a person with a genetic mutation called delta 32 that made them HIV-resistant. Researchers in California found traces of HIV in his tissue in July 2012, but Brown claims that the any virus that remains is dead and can't replicate.

29 However, a stem cell transplant is risky and has only been performed on people who may die from cancer. It is not a realistic treatment option for most people living with HIV, who can usually live normal, comfortable lives if they take antiretroviral drugs.

Any transplant requires weakening the immune system, which puts the patient at a 15 to 20 percent risk of death, the New York Times reported. A third HIV-positive patient who had received the same treatment as the Boston subjects died from cancer. The subjects' bone marrow donors did not have the delta 32 mutation.

"The next step is to confirm this in larger numbers," said Dr. Sharon Lewin, an infectious disease professor at Monash University in Melbourne, Australia, told MedPage Today.

Lewin, who did not treat the Boston patients, added that she did not believe that the stem cell treatment would become widespread because of the risk and money involved. However, patients who undertake the treatment are "absolutely instrumental in moving the science forward."

There has been another way HIV has apparently been cured in humans. A baby who was born infected with HIVhas had no traces of the virus for more than 2 and a half years after receiving treatment shortly after she was born. Doctors at the University of Mississippi began giving the HIV-positive infant aggressive three-drug HIV treatments within 30 hours of her birth. The medications appear to have removed HIV from the baby's bloodstream before the body was able to store the virus, which can replicate in a person's system after treatment is stopped.

The World Health Organization pushed for earlier treatment of HIV earlier this week. Currently, most countries including the U.S. recommend beginning antiretroviral therapy (ART) when a patient's CD4 cells (also known as T-cells) drop below 350 cells/mm3.

The WHO now recommends treatment begin as soon as the person's cell count drops below 500 cells/mm3. They also pushed for ART for all children under 5 with HIV, all pregnant and breastfeeding women with HIV and all HIV-positive people who have one partner who is uninfected.

Source: http://www.cbsnews.com/news/two-men-cured-of-hiv-no-longer-taking-treatments

New research gives hope of finding HIV cure

Acces video: http://aje.me/11ikdF1

Scientists in the United States say there is growing evidence they may have stumbled across a treatment, if not a cure, for AIDS.

There has been one case of this happening before.

But now they have revealed that two more HIV positive men, who had bone marrow transplants as part of cancer treatment, have no detectable levels of the virus in their blood.

Al Jazeera's Tarek Bazley reports.

Source: http://www.aljazeera.com/video/americas/2013/07/20137313265706867.html

Patients HIV-free for now after transplant

By Saundra Young, CNN July 4, 2013 -- Updated 1051 GMT (1851 HKT)

Experts are hailing a new development as a potentially important step in the fight against HIV.

STORY HIGHLIGHTS

 Two men show no sign of HIV after bone marrow transplants  But experts say it's too early to know if the two are cured  The transplant isn't a viable option for the vast majority of patients

(CNN) -- Two more HIV patients have no signs of the virus in their blood following bone marrow transplants, according to the Boston researchers who treated them.

However, experts stopped short of calling the two cured and said the treatment is not a viable option for the majority of HIV patients.

The findings were presented Wednesday at the International AIDS Society Conference in Kuala Lumpur, Malaysia.

The two men, whose identities are being withheld, had been on antiretroviral (ARV) drug therapy for years before being diagnosed with lymphoma, a cancer of the lymph nodes.

Both underwent intensive chemotherapy followed by bone marrow transplants to treat the cancer. They remained on antiretroviral therapy.

32 AmfAR CEO discusses toddler's HIV 'cure'

Approximately four months after the transplant doctors were still able to detect HIV in their blood, but six to nine months later, all traces of the virus were gone.

"Because of those findings, we thought it was justified to take the patients off of their therapy to see what happens," said Dr. Timothy Henrich, who conducted the clinical trial.

"Now, in a normal person who has HIV, who has been on long-term antiretroviral therapy for years, usually the virus comes back within two to four weeks after stopping therapy, it comes right back. "

Some patients make it up to eight weeks before the virus returns, said Henrich, a researcher at Harvard Medical School and Brigham and Women's Hospital in Boston, but the virus returns eight to 10 weeks after therapy is stopped in the vast majority of patients.

HIV discovery 'will change your life forever'

Not so for these two, however.

"We are now recording 15 weeks after therapy and eight weeks after therapy for our two patients, and to date we are unable to detect HIV rebounding in the bloodstream after we stopped the therapy," Henrich said.

"We do weekly monitoring, as well. We've been looking at the virus in the blood and the cells in the blood essentially every week since we've taken them off therapy, and we have not been able to detect virus at this time."

The two men are being compared to Timothy Ray Brown, also known as the "Berlin Patient." Brown is thought to be the first person ever "cured" of HIV/AIDS.

In 2007, Brown had a stem cell transplant to treat his leukemia. His doctor searched for a donor with a rare genetic mutation called CCR5 delta32 that makes stem cells naturally resistant to HIV infection.

Today, the virus is still undetectable in Brown's blood, and he is still considered to be "functionally cured." A functional cure means the virus is controlled and will not be transmitted to others.

The stem cell transplant procedure, however, is very dangerous because a patient's immune system has to be wiped out in order to accept the transplant.

Using a bone marrow transplant to treat HIV is not a feasible treatment for most patients, and only 1% of Caucasians -- mostly Northern Europeans -- and no African-Americans or Asians have the CCR5 delta32 mutation, researchers say.

The transplant is still not a practical strategy for the majority of HIV patients, and the risk of mortality is up to 20%, Henrich says.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, agreed.

33 "This is not a practical approach for someone who does not need a stem cell transplant since the transplant and its preparation and its subsequent need for chronic immunosuppression is a risky procedure," Fauci said.

"If you have an underlying neoplasm (tumor) like these patients had, then the risk outweighs the benefit," he said. "However, if you are doing well on ARVs and you merely want to get off antiretroviral therapy, then the risk seems greater than the benefit."

HIV 'cure' in toddler offers 'global hope'

Even though the two patients showed a reduction of the virus in the blood, it could still be in some tissue -- the brain or gastrointestinal tract, for instance, Henrich said.

The virus "could certainly return," he said.

"It's possible, again, that the virus could return in a week, it could return in a month -- in fact, some mathematical modeling predicts that virus could even return one to two years after we stop antiretroviral therapy, so we really don't know what the long-term or full effects of stem cell transplantation and viral persistence is."

Still, he feels the information will help move the curative field of HIV research forward.

"We're going to learn different strategies about how we can attack the viral reservoir, how we can harness the immune system better and what exactly caused the lack of virus in the two patients at least in the short term."

Earlier this year, researchers said an HIV-positive baby in Mississippi was given high doses of three antiretroviral drugs within 30 hours of her birth, with doctors hoping that would control the virus.

Two years later, there is no sign of HIV in the child's blood, making her the first child to be "functionally cured" of HIV.

The Foundation for AIDS Research, or amfAR, helped fund the study.

"These findings clearly provide important new information that might well alter the current thinking about HIV and gene therapy," said amfAR CEO Kevin Robert Frost.

"While stem cell transplantation is not a viable option for people with HIV on a broad scale because of its costs and complexity, these new cases could lead us to new approaches to treating, and ultimately even eradicating, HIV."

"Dr. Henrich is charting new territory in HIV eradication research," said Dr. Rowena Johnston, amfAR vice president and director of research.

"Whatever the outcome, we will have learned more about what it will take to cure HIV. We believe amfAR's continued investments in HIV cure-based research are beginning to show real results and will ultimately lead us to a cure in our lifetime."

In the meantime, Henrich says he and other groups are actively enrolling patients for these types of studies.

Source: http://edition.cnn.com/2013/07/03/health/hiv-patients

Two more men with HIV now virus-free. Is this a cure?

By Maggie Fox NBC News 7/26/2012

Two men unlucky enough to get both HIV and cancer have been seemingly cleared of the virus, raising hope that science may yet find a way to cure for the infection that causes AIDS, 30 years into the epidemic.

The researchers are cautious in declaring the two men cured, but more than two years after receiving bone marrow transplants, HIV can't be detected anywhere in their bodies. These two new cases are reminiscent of the so-called "Berlin patient," the only person known to have been cured of infection from the human immunodeficiency virus.

These two cases, presented as a “late-breaker” finding on Thursday at the 19th annual International AIDS Conference in Washington, D.C., are among the reasons that scientists have been speaking so openly at the event about their hopes of finding a cure.

“Everyone knows about this ‘Berlin patient’. We wanted to see if a simpler treatment would do the same thing”, said Dr. Daniel Kuritzkes of Brigham and Women’s Hospital in Boston, who oversaw the study. The widely publicized patient, Timothy Brown, was treated for leukemia with a bone marrow transplant that happened to come from a donor with a genetic mutation that makes immune cells resist HIV infection. The transplant replaced his own infected cells with healthy, AIDS-resistant cells. He is HIV-free five years later.

AIDS patients are susceptible to cancers, but they usually stop taking HIV drugs before receiving cancer treatment. “That allows the virus to come back and it infects their donor cells,” Kuritzkes said.

About 34 million people are infected with HIV, the virus that causes AIDS, globally; 25 million have died from it. While there’s no vaccine, cocktails of powerful antiviral drugs called antiretroviral therapy (ART) can keep the virus suppressed and keep patients healthy. No matter how long patients take ART, however, they are never cured. The virus lurks in the body and comes back if the drugs are stopped. Scientists want to flush out these so- called reservoirs and find a way to kill the virus for good.

Brown, and now these two other men, offer some real hope.

Dr. Timothy Henrich and colleagues at Brigham and Women’s Hospital launched a search about a year ago for HIV patients with leukemia or lymphoma who had received bone marrow stem cell transplants. Bone marrow is the body's source of immune system cells that HIV infects and it’s a likely place to look for HIV’s reservoirs.

“If you took an HIV patient getting treated for various cancers, you can check the effect on the viral reservoirs of various cancer treatments,” Kuritzkes, who works with Henrich, said. They found the two patients by asking colleagues at Dana-Farber Cancer Institute in Boston which, like Brigham and Women’s, is associated with Harvard Medical School.

Both men had endured multiple rounds of treatment for lymphoma, both had stem cell treatments and both had stayed on their HIV drugs throughout. “They went through the transplants on therapy,” Kuritzkes said.

It turns out that was key.

35 “We found that immediately before the transplant and after the transplant, HIV DNA was in the cells. As the patients’ cells were replaced by the donor cells, the HIV DNA disappeared,” Kuritzkes said. The donor cells, it appears, killed off and replaced the infected cells. And the HIV drugs protected the donor cells while they did it.

One patient is HIV-free two years later, and the other is seemingly uninfected three-and-a-half years later.

“They still have no detectable HIV DNA in their T-cells,” Kuritzkes said. In fact, doctors can’t find any trace of HIV in their bodies -- not in their blood plasma, not when they grow cells in the lab dishes, not by the most sensitive tests.

Can the patients be told they are cured?

“We’re being very careful not to do that,” Kuritzkes said.

For now, both men are staying on AIDS drugs until they can be carefully taken off under experimental conditions. "We are not saying, “You are like the Berlin patient’.”

Although the men are HIV-free, Kuritzkes says it's been an arduous experience for them. After being diagnosed HIV-positive, one underwent rounds of chemotherapy for Hodgkin’s disease, a kind of lymphoma, before receiving the final bone marrow transplant, called an allogeneic bone marrow transplant. It is not an easy treatment to endure.

The men, one from Boston and one from New York, were not initially told their HIV had seemingly disappeared. When researchers realized news media would cover the report, they were informed.

Neither man is being identified for privacy reasons but one is in his 50s and has been infected since the beginning of the AIDS epidemic in the early 1980s. The other man, in his 20s, was infected at birth.

The findings may not apply to all patients. Both men were a little unusual in that they had a genetic mutation that can make immune cells resistant to infection by HIV. Their new immune cells, however, which came from the donors, are fully susceptible to the virus.

“We’re never really going to be able to do bone marrow transplants in the millions of patients who are infected,” Kuritzkes said. “But if you can stimulate the virus and eliminate those cells, we can protect the remaining cells from being infected.”

Separately, two other studies presented at the conference have scientists optimistic about a cure. In one, a cancer drug called vorinostat flushed out latent HIV from a handful of patients, offering the possibility of killing these latent reservoirs. In another, about 15 French patients who got HIV drugs very early after their infections were able to stop treatment and don’t show any symptoms years later, even though they are still infected.

Organizers of the conference say the findings provide an argument for treating patients early. “(These studies) give us reason for enthusiasm, that ultimately we are going to get to where we needed to go, which is to cure people with HIV infection,” said Dr. Steven Deeks, an HIV expert at the University of California, San Francisco.

Source: http://www.nbcnews.com/id/48338421/ns/health-mens_health/t/two-more-men-hiv-now-virus-free- cure/#.UuOkrfaCG3U

36 Newspapers, magazines and blogs

After Marrow Transplants, 2 More Patients Appear H.I.V.-Free Without Drugs

By DONALD G. McNEIL Jr. Published: July 3, 2013

Two H.I.V.-infected patients in Boston who had bone-marrow transplants for blood cancers have apparently been virus-free for weeks since their antiretroviral drugs were stopped, researchers at an international AIDS conference announced Wednesday.

The patients’ success echoes that of Timothy Ray Brown, the famous “Berlin patient,” who has shown no signs of resurgent virus in the five years since he got a bone-marrow transplant from a donor with a rare mutation conferring resistance to H.I.V.

The Boston cases, like Mr. Brown’s, are of no practical use to the 34 million people in the world who have H.I.V. but neither blood cancer nor access to premier cancer-treatment hospitals.

But AIDS experts still find the Boston cases exciting because they are another step in the long and so-far- fruitless search for a cure. They offer encouragement to ambitious future projects to genetically re-engineer infected patients’ cells to be infection-resistant. At least two teams are already experimenting with variants on this idea, said Dr. Steven G. Deeks, an AIDS researcher at the University of California, San Francisco.

Dr. Françoise Barré-Sinoussi, a discoverer of the virus that causes AIDS and the president of the International AIDS Society, called the findings about the Boston patients “very interesting and very encouraging.” The announcement about the cases was made at the society’s annual conference in Kuala Lumpur, Malaysia.

Mr. Brown is sometimes referred to as the “first H.I.V. cure.”

But there are important differences between his case and those of the Boston patients. For example, no AIDS expert, including the doctors from Brigham and Women’s Hospital in Boston following the two patients, is using the word “cured” to describe their status. The technique used on them involves severely weakening the immune system before a marrow transplant. It is so dangerous that it is unethical to perform it on anyone not already at risk of dying from cancer, especially because most people with H.I.V. can live relatively normal lives by taking a daily antiretroviral cocktail.

One patient stopped taking antiretroviral drugs seven weeks ago. For the other, it has been 15 weeks. No virus or antibodies to the virus have been found in their blood or other tissues since.

Normally, when a patient stops the drugs, the virus bounces back in less than a month, but each person is different. “It could come back in a week, or in six months,” said Dr. Timothy Henrich, a doctor overseeing the two patients. “Only time will tell.”

The process the two patients underwent is risky — a third patient in the study died when his cancer returned — but somewhat less so than the procedure done on Mr. Brown. Mr. Brown had leukemia. The three Boston patients had lymphoma.

The Boston patients’ bone marrow, where new blood cells are made, was only partially destroyed by drugs before they were given new marrow from matching donors — a process that carries a 15 to 20 percent risk of death, Dr. Henrich said.

37 Mr. Brown’s marrow was completely obliterated by drugs and whole-body radiation, a procedure that kills 40 percent of the patients, and he had it done twice.

Mr. Brown’s new marrow came from a donor who was a close genetic match and had a rare mutation that makes a person virtually impervious to infection with H.I.V.

The mutation, known as delta 32, creates CD4 cells — the white blood cells that the virus attacks — lacking a CCR5 surface receptor, the “door” that the virus uses to enter the cell.

The donors for the Boston patients did not have the delta 32 mutation.

Unlike Mr. Brown, the Boston patients stayed on antiretroviral therapy throughout the lengthy transplant process and for years afterward. The drugs prevent the virus from replicating itself.

“The idea was to protect the new donor cells from becoming infected,” Dr. Henrich explained.

During that time, in a phenomenon known as graft-versus-host disease, the new cells were attacking their old, chemotherapy-weakened counterparts and clearing them from the body, a process that takes about nine months, Dr. Henrich said.

Because only the old cells were infected with H.I.V., the hope was that graft-versus-host disease would “mop up” all the viral reservoirs.

But runaway graft-versus-host disease can be fatal, so the two patients were intermittently on and off immunosuppressive drugs and steroids to control it.

One immunosuppressive drug, sirolimus, may also have helped kill off H.I.V., Dr. Henrich said.

It is known to prevent retroviruses like H.I.V. from replicating.

The two patients had transplants between two and five years ago. They had months of tests on their blood and tissues to make sure no H.I.V. or antibodies to it were found before Dr. Henrich and his research partner, Dr. Daniel Kuritzkes, proposed stopping the antiretroviral treatment.

For such tests, doctors remove immune cells and “activate” them with chemicals to make them reproduce. If any virus is hiding in the cells’ DNA, it is “spit out” and can be detected.

But doctors can never be sure that they have tested all the reservoirs where the dormant virus might hide. It is relatively easy, for example, to sample rectal but not brain tissue.

Since the patients stopped taking antiretrovirals, they “feel great and are leading completely normal lives,” Dr. Henrich said.

That distinguishes them from Mr. Brown, who has survived virus-free for more than five years but still has weakness and pain from his grueling anticancer regimen.

AIDS specialists are interested in the Boston patients because they offer new insights into how the immune system can be used to attack the virus.

Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, said it was “conceivable and maybe even likely” that their H.I.V. was permanently gone.

If so, he said, it would show that it is not necessary to find a matching donor who had the delta-32 mutation.

Dr. Deeks, the AIDS researcher in California, said the cases raised the question of when to say an H.I.V. patient has been “cured.”

38 “Should we wait six months to see if the virus rebounds?” he asked. “Or will we have to wait up to five years, as oncologists tend to do with cancer?”

Dr. Barré-Sinoussi, of the International AIDS Society, said she might eventually prefer to adopt the term oncologists use: “in remission.”

A version of this article appeared in print on July 4, 2013, on page A10 of the New York edition with the headline: After Marrow Transplants, 2 More Patients Appear H.I.V.-Free Without Drugs.

Source: http://www.nytimes.com/2013/07/04/health/post-transplant-and-off-drugs-hiv-patients-are-apparently- virus-free.html?_r=0

Two Long-Infected Patients Seem HIV-Free After Marrow Transplants

Optimism Grows That a Cure, Once Thought Out of Reach, Is Achievable

Two patients long infected with HIV appear to be free of the virus after undergoing bone-marrow transplants for lymphoma and eventually stopping AIDS treatment, researchers reported. By Ron Winslow

An HIV-solidarity candle display in El Salvador in May; a small group of cases is helping to fuel optimism among many AIDS researchers and activists that a cure is achievable. European Pressphoto Agency

Two patients long infected with HIV appear to be free of the virus after undergoing bone-marrow transplants and eventually stopping treatment with AIDS drugs, researchers reported Wednesday. The patients have been off antiretroviral therapy for just 15 and eight weeks respectively, which researchers said meant it was far too soon to say they had been [...]

Source: http://stream.wsj.com/story/latest-headlines/SS-2-63399/SS-2-268160/

July 3, 2013 6:52 pm Fresh hope for HIV cure after bone marrow transplants

By Andrew Jack in London Two patients with HIV who were given bone marrow transplants have shown no sign of a resurgence in infection several weeks after stopping antiretroviral medicine, in a fresh sign of hope for more radical new treatments for the disease.

In a report released at the International Aids Society conference in Kuala Lumpur, Timothy Henrich and Daniel Kuritzkes from the division of infectious diseases at Brigham and Women’s Hospital in Boston reported no detectable HIV in one patient after seven weeks and another 15 weeks after they ceased taking medication.

The two researchers calling the results “exciting” while cautioning that it was “too soon to determine if the men have been cured” following transplants late last year. They said they would need to continue close observations of the “Boston patients” at least for a year to be more confident about the findings.

But the development comes after several other recent reports of the apparent elimination of HIV, including in a baby born from a mother with HIV in Mississippi and a group of French patients treated with drugs rapidly after infection and no longer taking any medication.

That has fuelled recent discussions over the value of earlier use of antiretroviral therapy, at a time when the human immune system is less compromised and may be able to fight off infection.

Stem cell transplantation, which already led to the apparent elimination of the virus from Timothy Brown, the so-called Berlin patient, is an extreme and costly procedure that will prove difficult to replicate widely, but may help researchers identify new ways to tackle treatment.

I remain prudent on the idea of a total elimination of the virus - Françoise Barré-Sinoussi, Pasteur Institute

But researchers are also examining the scope for drugs and therapeutic vaccines as well as early use of existing therapies to help treat and reduce the risk of infection of others.

41 Françoise Barré-Sinoussi from the Pasteur Institute in Paris and president of the International Aids Society, the leading network of researchers in the field, has been co-ordinating efforts to pursue a cure.

She told the FT recently: “I remain prudent on the idea of a total elimination of the virus, which remains latent in all the bodily organs and the brain. It’s practically mission impossible. But a functional cure, which exists in the natural state? We should be capable of inducing it.”

Over the weekend, the World Health Organisation unveiled new treatment guidelines recommending use of drugs once a patient’s CD4 count, a measure of the immune response, fell below 500 cells per cubic millimetre compared with 350 at present. That would make an estimated additional 9m patients eligible for treatment bringing the total to 27m, of which just 11m are on therapy.

Source: http://www.ft.com/intl/cms/s/0/a009385a-e400-11e2-b35b-00144feabdc0.html#axzz2Y2gNDNhU

No sign of HIV return in bone marrow transplant patients, say scientists Two men who had longstanding HIV infections have stopped taking Aids drugs and have no detectable HIV in their blood.

Sarah Boseley, health editor

Wednesday 3 July 2013 09.30 BST

Timothy Henrich of the Harvard-affiliated Brigham and Women's Hospital in Boston speaks at the International Aids Society Conference in Kuala Lumpur. Photograph: Lai Seng Sin/AP

Two men who became free of HIV infection after bone marrow transplants have stopped taking Aids drugs without any sign of the virus returning, according to scientists.

Talk of a cure is premature, the doctors told the International Aids Society conference in Kuala Lumpur, but the news will raise hopes that progress can be made towards a treatment that will not only keep the virus at bay but eventually eradicate it.

The two men, who had longstanding HIV infections, were given bone marrow transplants at the Dana- Farber/Brigham and Women's Cancer Centre in Boston because they were suffering from cancers of the blood. Tests showed that as their own cells were replaced by cells from the bone marrow donor, the levels of virus in their blood steadily dropped to undetectable.

One of the men stopped taking antiretroviral medication to suppress HIV almost four months ago and the other seven weeks ago. They still have no detectable HIV in their blood cells.

"While these results are exciting, they do not yet indicate that the men have been cured," said Timothy Henrich, from the division of infectious diseases at Brigham. "Long-term follow up of at least one year will be required to understand the full impact of a bone marow transplant on HIV persistence."

One of the patients became infected with HIV in the early years of the epidemic, and the other was infected as a baby. They are both monitored frequently. Scientists have conducted extensive tests to try to find HIV not only in their blood cells but also in tissue and have not found anything, although they cannot be sure it is not there. HIV is able to hide and remain at low levels but remain capable of becoming active.

The virus could still be present in an organ such as the brain or in the gastrointestinal tract, Henrich said. "If the virus does return, it would suggest that these other sites are an important reservoir of infectious virus and new approaches to measuring the reservoir at relevant sites will be needed to guide the development of HIV curative strategies."

43 Even if the virus does not reappear, bone marrow transplants are not feasible for everybody. There is a 15-20% mortality rate and the patient has to take drugs to suppress their immune system thereafter. But the experiences of the two men will teach scientists a great deal more about how to combat the virus.

The International Aids Society, which brings together researchers in the field worldwide, has led efforts towards a hunt for a cure for HIV infection as successive attempts to design a vaccine have failed.

The case of the "Berlin patient", later identified as American Timothy Ray Brown, was proof that a cure was possible. Brown underwent a stem cell transplant because of cancer, but his doctors managed to find a donor who had genetic resistance to HIV – a rare thing. Brown has been cured of both HIV infection and cancer, but the treatment carries major risks and is hugely expensive, and it would be very unlikely that many donors with genetic resistance to the virus could be found.

In March it was announced that a child born with HIV in Mississippi had been "cured" by being given very prompt antiretroviral therapy after birth. The child's mother stopped giving the baby drugs at around the age of 18 months and no longer went for regular checks to the hospital. When they returned five months later, the child had no detectable virus. Scientists are uncertain why it happened, but speculated that the early use of drugs – within 30 hours of the birth – may have prevented the virus taking hold.

Henrich said he was cautious but excited about the scientific developments. "Five years ago if you'd mentioned a cure, research people wouldn't have taken you seriously," he said. "We're not there yet. Are we close? Probably not, but who knows? This could be a rapid learning curve in the next few years."

Source: http://www.com/society/2013/jul/03/hiv-bone-marrow-transplant

Bone marrow transplant success ‘may hold key to HIV treatment’

44 Two men have no detectable HIV in their blood cells months after stopping therapy / Mehau Kulyk Chris Smyth Health Correspondent July 4 2013

Two men appear to have been cured of HIV infection after bone marrow transplants in an advance that experts say offers new avenues towards treatments for millions of patients worldwide.

The men have no detectable HIV in their blood cells months after stopping antiretroviral therapy and researchers say they are “very optimistic and excited” about their future progress.

Unlike Timothy Ray Brown, the first person known to have been cured of HIV, the patients in Boston did not receive cells from a donor with a genetic mutation offering resistance to the virus. The men, who have not been named, received…

Source: http://www.thetimes.co.uk/tto/health/news/article3806826.ece

Two HIV-infected men treated with bone marrow transplants 'have no detectable Aids virus'

STEVE CONNOR SCIENCE EDITOR

WEDNESDAY 03 JULY 2013

Two men infected with HIV for many years have been able to stop taking anti-viral drugs following bone-marrow transplants without any detectable Aids virus in their bodies, scientists have announced.

45 A range of highly sensitive tests have failed to detect HIV in either man, suggesting that the transplanted immune systems of the patients may have been able to clear the viral "reservoir" of HIV from their bodies.

UPDATE 12 December 2013: HIV patients ‘cured’ of Aids suffer relapse

The findings point to a possible "functional" cure for Aids based on the eradication of HIV from a patient's cells. However, the scientists emphasised that it is still too early to say whether the patients have been truly cured of HIV as the virus may still return.

A number of previous studies have suggested that it may be possible to eradicate HIV completely from a patient's body based on transfusions of bone marrow stem cells, which replace the white blood cells that the Aids virus attacks.

Until recently, scientists thought that it would not be possible to cure someone of HIV as the virus integrates its genetic material into the DNA of the patient, where it can lie dormant for many years even in the presence of anti-viral drugs.

Both patients were taking anti-retroviral drugs prior to and during the period when they underwent the bone-marrow transplants to treat cancer but this was withdrawn when doctors realised that their HIV had fallen to undetectable levels.

One patient has been repeatedly tested for HIV for nearly 4 months following his withdrawal from antiviral therapy with no signs of the virus returning. The second patient shows no signs of being infected with HIV seven weeks after stopping his drug treatment.

"So far to date, we cannot detect virus in peripheral blood, we cannot detect virus integrated into the cells of the patients," said Dr Timothy Henrich of the Brigham and Women's Cancer Centre in Boston, who led the study released at the International Aids Society conference in Kuala Lumpur, Malaysia.

"I want to stress that longer term follow-up is going to be needed to understand the full impact of stem-cell [bone marrow] transplantation….It is possible that the virus could come back in a few months from now, or it's possible that it could take one or two years for the virus to return to these patients," Dr Henrich said.

"Even with a large reduction in the HIV reservoir, you could still potentially have rebound. So we will don't know the full implications of the findings," he said.

The two Boston patients were given bone marrow transplants from donors who were susceptible to HIV infection. This differs from the case of the "Berlin patient", an American gay man called Timothy Brown who received a bone marrow transplant from a donor carrying a mutation that appears to confer a type of immunity to HIV.

46 Dr Henrich said that although the findings are interesting, bone marrow transplants are not practical for the vast majority of people with HIV. Not only it is costly, but it is potentially dangerous, with a mortality rate of 20 per cent for cancer patients, he said.

SCIENTISTS TALKING OF 'FUNCTIONAL CURE'

A cure for Aids was once thought to be impossible given that HIV is able to hide away within the cells of the body, lying dormant for many years, and possibly a lifetime, even when the bloodstream is swamped with a powerful cocktail of antiretroviral drugs.

However, scientists are now talking of something called a "functional cure". In other words, it may be possible to prevent HIV from re-emerging by some clever trick based on tinkering with a patient's immune system.

Timothy Brown, the co-called Berlin patient, became HIV free following a bone-marrow transplant to treat cancer. His marrow donor appears to have passed on a genetic resistance to HIV infection.

A baby in Mississippi, infected during birth, also seems to have shrugged off the virus, as have a group of patients in France known as the Visconti cohort. Now two patients in Boston appear to have become HIV free following bone-marrow transplants from a donor who, unlike Mr Brown's donor, is susceptible to HIV infection.

What these cases show is that there may just be an alternative approach to long-term antiretroviral drugs. It is early days, but a functional HIV cure may just be possible.

Source: http://www.independent.co.uk/life-style/health-and-families/health-news/two-hivinfected-men-treated- with-bone-marrow-transplants-have-no-detectable-aids-virus-8685645.html

Boston researchers report hopeful findings on HIV

By Kay Lazar | Globe Staff July 03, 2013

Boston researchers are reporting an intriguing finding in two of their patients with longstanding HIV infections that may bolster a new approach to fighting the disease.

The Brigham and Women’s Hospital scientists say the patients, who underwent bone marrow transplants several years ago for cancer, have no detectable levels of HIV in their blood cells anymore, despite recently stopping powerful antiretroviral medications that are typically given to those infected with the virus.

“I don’t want to use the ‘cure’ word,” said Dr. Timothy Henrich, a Brigham infectious diseases associate physician who is leading the study. “If they remain virus-free in a year, or even two years, after [stopping] therapy, then we can make a statement that the chances of the virus returning are very low.”

Henrich’s team is presenting its findings Wednesday at the International AIDS Society Conference in Malaysia.

Last summer, Henrich and coauthor Dr. Daniel Kuritzkes announced that HIV, the virus that causes AIDS, was easily detected in the patients’ blood prior to their bone marrow transplants but could not be found eight months after the transplant.

At that time, the men remained on HIV medications — prompting some scientists to express skepticism, because they linked the apparent disappearance of the patients’ virus to their continued HIV medications, and not the bone marrow transplants.

Since then, the two patients stopped taking the medications, with one coming off 15 weeks ago, and the other seven weeks ago.

48 The researchers are carefully testing the patients’ blood weekly, and say they have not found signs of HIV. Henrich said they also removed and tested a tiny piece of tissue from one of the patient’s intestines — where the wily HIV virus is believed to lurk — and that came back negative, too.

“HIV could still be hiding in the brain, gut or lymph nodes,” Henrich said.

Dr. Jay Levy, an HIV researcher at the University of California, San Francisco, said the Boston results are encouraging but the patients need to be monitored much longer to know whether the virus has been truly knocked out.

The Boston patients both suffered from Hodgkin’s lymphoma, a cancer of the blood. After chemotherapy and other treatments failed, doctors performed bone marrow transplants to replace the patients’ cancerous blood cells with healthy donor cells. They discovered that within eight to nine months of the transplants, the patients’ blood showed no trace of HIV, and the patients have also remained cancer free.

The Boston findings are similar to results widely reported in 2009 by German doctors who said that an American, Timothy Ray Brown, was given a bone marrow transplant for leukemia and appeared to have been cured of HIV, too. He is believed the only patient cured of HIV.

But Brown, known as the “Berlin patient,” received bone marrow from a donor who carried a rare gene mutation, CCR5-delta32, which is thought to provide resistance to HIV. Previously, researchers had not observed similar results with ordinary donor cells, such as those given to the Boston patients.

Henrich and other researchers say bone marrow transplants, which are risky and can be lethal, are not a practical or ethical approach to treating HIV, especially in patients who do not have cancer. But the Boston findings may help researchers better understand how and where HIV persists in the body, and also determine whether the rare CCR5-delta32 mutated genes would be needed to achieve a cure using an approach other than transplanting bone marrow from a donor.

Levy’s lab is studying whether bone marrow cells extracted from someone infected with HIV can be genetically altered to resemble the CCR5-delta32 mutation. The goal is to give HIV patients their own genetically altered cells to wipe out the virus, while not exposing them to the risk of traditional bone marrow transplantation of a patient’s immune system rejecting the donor’s cells.

Henrich said his team worked closely with the patients’ cancer specialists, an independent board at the hospital that monitors research, and outside specialists to ensure the patients were not pressured to take part in the study, and that they understood that stopping their HIV medications carries a risk of the virus resurfacing.

“This is unknown territory and we made that very clear to the patients, who are both very curious to know if they still have HIV in their bodies,” Henrich said.

The two, who were not identified, were “very positive” about participating to help further research, Henrich said. Still, they are anxious.

“They have been taking anti-retroviral therapy for years and years,” he said, “and all of a sudden their research doctors are telling them to stop taking it.”

All agreed that if HIV is detected in the patients, they will be returned to antiretroviral medications, he said.

Source: http://www.bostonglobe.com/lifestyle/health-wellness/2013/07/03/boston-researchers-report- encouraging-hiv-findings/giM6hLBmUgpT0UmgKns9PK/story.html

Deux patients greffés «guéris» du sida Fréour, Pauline 03/07/2013 | Mise à jour : 14:52

Deux hommes séropositifs ayant subi une greffe de moelle osseuse ne présentent plus de traces de VIH plusieurs mois après l'arrêt de leur traitement antirétroviral.

Même si la compréhension du phénomène est encore incomplète, les résultats présentés mercredi lors d'un congrès international en Malaisie sont intéressants. Deux patients séropositifs ayant subi une g...

Source: http://recherche.lefigaro.fr/recherche/access/lefigaro_fr.php?archive=BszTm8dCk78atGCYonbyzoOj0qJlGZ8As T7xEE24Net0WSag1w0w3oRfG8df4oAwu2IGtjAq08M%3D

Matthew Herper, Forbes Staff. I cover science and medicine, and believe this is biology's century.

Hint To A Cure? Two Men Remain HIV Free After Bone Marrow Transplants 7/03/2013 HIV-1 particles assembling at the surface of an infected white blood cell. (Photo credit: Wikipedia)

Two patients in whom HIV seemed to vanish after they were given bone marrow transplants to treat cancer remained free of the virus even after stopping treatment with HIV medicines. The result yields growing hope that the virus could someday be cured, not just kept in check with a cocktail of medicines as it is now. The results of the study are being presented at a meeting of the International AIDS Society in Kuala Lumpur, Malaysia.

Data on the same two patients was presented a year ago at a conference in Washington D.C. by the same researchers, Timothy Henrich and Daniel Kuritzkes. But at the time the patients had not stopped taking their AIDS medicines.

Bone marrow transplants are grueling and expensive procedures, and are not likely to be used for patients whose disease can be controlled with existing drug cocktails. But scientists hope that these cases could provide clues to new ways of trying to eradicate the virus from the body.

Both went to Brigham and Women’s Hospital in Boston for treatment for blood cancer, and eventually required that the stem cells in their bone marrow — which create the immune cells that fight disease and that are infected with the human immunodeficiency virus — be replaced as a treatment. Unlike most bone marrow transplant recipients, they did not ever stop taking their AIDS medicines to take chemotherapy. Doctors have theorized that this kept HIV levels low enough that their new immune cells were never infected.

51 Now the patients have stopped taking their AIDS drugs, one for 7 weeks and the other for 15 weeks. So far, the virus has not returned. The researchers warn in two press releases and a scientific abstract that were made available to Forbes before publication that the patients cannot yet be said to be cured and that the virus might still come back.

One man, Timothy Brown, an American treated in Berlin, is thought to have been cured by a stem cell transplant. His transplanted bone marrow cells had a mutation in a gene called CCR5 that prevented the HIV virus from infecting them. It had been thought this might explain the cure, and that helped lead Sangamo, a U.S. biotechnology company, to develop an experimental gene therapy that tries to modify that gene. The Brigham cases seem to indicate that a cure may not require a mutation in CCR5.

“There was a sense that Timothy Brown’s immune system had been given an armor coating,” says Kevin Robert Frost, chief executive of amfAR: The Foundation for AIDS Research. But the new data suggest that changing CCR5 may not be the critical piece to clearing the HIV virus. Tim Brown’s cure may have made him immune to HIV forever because it gave him immune cells with this mutation, though, while the two men treated at the Brigham could be infected again, Frost says. He says that many companies are trying different techniques to try and cure HIV.

In March, reports said that an infant may also have been cured of HIV by intensive treatment that began soon after infection. Together, these cases are leading to hope that one day HIV might be cured. But researchers at the meeting warn that it could be many years before any such cure becomes available, if it ever does.

“I don’t think anybody expects a single cure is going to work for everyone, at least not yet,” says Frost, the amfAR CEO. “We all see having a multiplicity of options as a very, very good thing.”

The studies at the Brigham were also supported by the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation.

Update July 4, 2014: Edward Lanphier, President and CEO, Sangamo Biosciences, sent me the following statement:

We read with interest your article on data presented at the meeting of the International AIDS Society earlier this week (“Hint to a Cure?: Two Men Remain HIV Free After Bone Marrow Transplants,” July 3, 2013). The story notes the difference between the Brigham and Women’s approach used in these two patients. with the approach developed by Sangamo. The latter technique utilizes our zinc-finger nuclease (ZFN)-mediated genome editing technology to create the CCR5 mutation that essentially blocks HIV from infecting the immune system.

Many clinicians would agree, however, that the three possible treatment options described in the article— including that used in the two highlighted cases– are not practical in a treatment setting, or may present too many safety and tolerability risks for the vast majority of HIV-infected patients. Sangamo’s approach, now in a Phase Two clinical study, seeks to replicate the dramatic and enduring benefit seen both in the case of Timothy Brown (“The Berlin Patient”), and in many patients naturally resistant to HIV infection. Additional Sangamo studies have found that the ZFN-based treatment creates a reservoir within the immune system of T-cells resistant to HIV infection. The ZFN-based therapy appears to be well- tolerated in patients studied to date, and may provide HIV-infected patients with a means of controlling the virus without further treatment. We await completion of our ongoing clinical studies later this year.

Source: http://www.forbes.com/sites/matthewherper/2013/07/03/two-patients-remain-hiv-free-after-bone- marrow-transplants

Bone marrow transplants could be the cure for HIV

Wednesday 3 Jul 2013

Researcher Timothy Henrich speaks at the International AIDS Society Conference in Kuala Lumpur, Malaysia (Picture: AP)

A cure for HIV seems to have moved a step closer after two patients were freed of the virus thanks to bone marrow transplants.

The HIV-positive men, who had the stem cell implants to fight blood cancer, have shown no signs of the virus returning and have both stopped taking anti-retroviral drugs.

Researcher Timothy Henrich said: ‘They are doing very well. While these results are exciting, they do not yet indicate that the men have been cured. Only time will tell.’

One of the patients ended his course of anti-retrovirals 15 weeks ago but was still showing no signs of the HIV returning.

The other also appeared to be HIV-free after seven weeks without the drugs.

Both of the men will have their cells, plasma and tissue tested for at least a year to give more of an idea of the implants’ effect on the virus.

The doctors fear it could be lying dormant in their bodies and reappear.

Kevin Robert Frost, chief executive of The Foundation Of AIDS Research said the findings could change the shape of HIV and gene therapy.

He added: ‘While stem cell transplantation is not a viable option for people with HIV on a broad scale, these new cases could lead us to new approaches to treating, and ultimately even eradicating, HIV.’

Dr Henrich, who led the research with Daniel Kuritzkes of the Harvard-affiliated Brigham and Women’s Hospital in Boston, announced their findings at an Aids conference in Kuala Lumpur.

Source: http://metro.co.uk/2013/07/03/bone-marrow-transplants-could-be-the-cure-for-hiv- 3868050/?ITO=news-sitemap

2 Men with HIV who had bone marrow transplants remain virus-free

A scanning electron micrograph of HIV particles infecting a human T cell. HIV researchers are meeting this week in Kuala Lumpur, Malaysia. (National Institute of Allergy and Infectious Diseases )

By Eryn Brown July 3, 2013

Two HIV-positive lymphoma patients who received bone marrow transplants to treat their cancer no longer have detectable virus in their blood cells — even after stopping antiretroviral therapy in recent weeks, researchers reported Wednesday at the International AIDS Society Conference in Kuala Lumpur, Malaysia.

While saying it was too early to declare the men cured, Dr. Timothy Henrich and Dr. Daniel Kuritzkes, both of the division of infectious diseases at Brigham and Women’s Hospital in Boston, called the results “exciting” and said they would help guide scientists’ efforts to fight HIV.

But bone marrow transplants are highly unlikely to become a standard therapy for people with HIV, Henrich said in an interview with The Times.

The news arrives on the heels of several interesting cases where HIV has, apparently, been eradicated in infected patients. In 2007, Timothy Brown, the so-called Berlin Patient, received a bone marrow transplant to treat leukemia; his marrow donor had a mutation that provided resistance to the strain of HIV that Brown had. After a second transplant in 2008, his leukemia was gone. So was his HIV infection. He reportedly remains HIV-free.

In March 2013, doctors reported that a 2-year-old girl in Mississippi had been “functionally cured” of HIV after receiving unusually aggressive antiretroviral treatment shortly after her birth. The girl’s treatments were interrupted when her mother began missing medical appointments — but even after a five-month lapse in treatment, doctors couldn’t detect HIV in her blood.

54 The two patients in Boston, both men, had been HIV-positive for many years before developing lymphoma, a blood cancer that can be treated, and sometimes even cured, through bone marrow transplants — which essentially give patients new, healthier immune systems.

Like Brown, the men had bone marrow transplants, but of a different sort. The chemotherapy they received before their operations was gentler than that Brown had, leaving more of their original blood cells intact and allowing them to continue their antiretroviral drugs. The transplants they received were of normal cells that did not have the mutation that protects against HIV.

One of the men received his transplant about 4.5 years ago; the other, 2.8 years ago. (A third patient also received a transplant, but died of lymphoma.) At last year’s International AIDS Conference in Washington, Henrich and Kuritzkes reported that after the procedures, neither surviving man had HIV in his blood — but both had continued taking antiretroviral drugs to make sure the virus stayed at bay.

This year, both men dropped the drug regimen, with one patient stopping his medication 15 weeks ago and the other seven weeks ago. When the scientists screened the men’s blood again, collecting billions of cells, they found that the virus was still undetectable — they had achieved at least a 1,000- to 10,000-fold reduction in the virus in the blood.

The team also tested rectal tissue (a major reservoir for the HIV virus) from one of the patients. There, too, the virus was undetectable.

Henrich, who noted that the virus could still be lurking in the patients’ bodies — in brain tissue, for instance — said he was “of the camp where I don’t know if I will ever be able to say patients are cured,” but that if the men remained HIV-free for a year or two, “the chances of the virus coming back will be very small.”

That said, he added, it doesn't make sense to perform bone marrow transplants to treat HIV-positive people who don’t have cancer. There are many risks associated with the expensive procedure, with 15% to 20% of patients dying from complications from the treatment itself rather than their cancer, Henrich said.

“Unfortunately, it’s not going to be a practical strategy,” he said.

But he also said the data the team had gathered would help guide new strategies for eradicating the virus.

“It will help us figure out what’s going on in terms of viral persistence,” Henrich said. “How low do we need to get the viral counts? How can we use the immune system to fight it?”

Source: http://www.latimes.com/news/science/sciencenow/la-sci-sn-hiv-bone-marrow-transplant- 20130703,0,2127995.story#ixzz2rQoHHEeu

Bone-marrow transplants 'cure' men with HIV

11:13 03 July 2013 by Andy Coghlan

Two men known only as the "Boston patients" have both stopped taking their anti-HIV medications following transplants of bone-marrow stem cells that appear to have banished the virus from their bodies.

They are the latest in a series of people with HIV who appear to be practically rid of the virus – although researchers warn it is too soon to declare them cured. Earlier this year, reports emerged of an infant and a group of 14 adults who all experienced functional HIV cures, meaning that although their bodies still had traces of the virus, it was no longer active.

So far, these functional cures have all been attributed to very early treatment with antiretroviral drugs, before the virus could take hold. The Boston patients, in contrast, are free of the virus thanks to a combination of a bone marrow transplant plus continuing antiretroviral drugs to stop newly donated immune cells from being infected.

Tim Henrich of Brigham and Women's Hospital in Boston, Massachusetts, who led an investigation into the men's condition, says that the men remain virus-free between three and four years after their transplants, even though they gave up taking antiretrovirals 15 and 7 weeks ago respectively. He presented the latest results today in Kuala Lumpur, Malaysia, at the annual meeting of the International AIDS Society.

Cure not confirmed

"While these results are exciting, they do not yet indicate that the men have been cured," says Henrich. "Long- term follow-up of at least one year will be required to understand the full impact of a bone-marrow transplant on HIV persistence."

Both of the Boston men were already HIV-positive when they were diagnosed with Hodgkin's lymphoma, a type of blood cancer. They both had standard chemotherapy to kill their native blood cells before undergoing a bone- marrow transplant from a donor to repopulate their blood. Until recently, both men also continued to take anti- HIV drugs in an effort to prevent any residual virus from infecting their "new" immune systems.

"Since coming off antiretroviral therapy this spring, the men continue to have no detectable HIV DNA or RNA in their blood," says Henrich.

There is one previous case of an HIV-positive individual being "cured" following a bone marrow transplant – the "Berlin patient", Timothy Ray Brown. But he owed his good fortune to the fact that his new bone marrow came from a donor whose blood cells had a mutated version of a protein called CCR5. HIV exploits the normal

56 version of this protein to enter cells, but cannot do the same with the mutated protein. So when the donated cells repopulated Brown's blood, they were all by default resistant to HIV.

The Boston patients, by contrast, received bone marrow from donors without this mutation. Henrich hopes to find out how the resulting blood cells remained uninfected despite this. He suspects that continued antiretroviral drug treatment was crucial.

Possible return

"Our patients remained on antiretroviral therapy throughout transplantation, and donor cells appear to be protected from infections during engraftment and replacement of host cells," he says. "But it's possible the virus could return in both of our patients in the coming weeks, months or even years."

"The result is very encouraging, but we need longer-term follow-up," says Françoise Barré-Sinoussi of the Pasteur Institute in Paris, France, who shared the 2008 Nobel prize in medicine for co-discovering HIV, and who was not involved in the Boston study.

"We need to understand better why these patients have undetectable virus," she says. "All the mechanisms need to be clarified, and then we can expect to develop another strategy for other patients that might not involve a transplant."

At the same symposium, Sharon Lewin of the Alfred Hospital in Melbourne and her colleagues revealed that a drug called entinostat has potential in the quest for an HIV cure. At present, all HIV-positive people must take antiretroviral drugs for life because the virus can hide in the body and re-emerge if treatment is halted. Entinostat, an anti-cancer drug, is the latest of a family of drugs that could lead to a full cure by reviving dormant virus and flushing it out into the bloodstream, where it can be killed by standard antiretroviral drugs.

Source: http://www.newscientist.com/article/dn23788-bonemarrow-transplants-cure-men-with-hiv.html

Double good news from HIV front line

03 July 2013 by Andy Coghlan

THE fight against HIV has taken a turn in our favour with news that the virus has all but disappeared in two infected people. Meanwhile, the World Health Organization (WHO) is opening up antiretroviral treatment to millions of infected people who do not currently qualify.

The two men were diagnosed with a blood cancer called Hodgkin's lymphoma after they had become HIV-positive. Three to four years ago they received chemotherapy to kill off white blood cells and the cells that produce them, before undergoing a bone marrow transplant to restore their blood systems.

58 A few months ago, the men came off antiretroviral drugs because levels of the virus had fallen to undetectable levels in their bodies. They remain apparently free of the virus.

"The donor cells appear to have been protected from infection during replacement of host cells," says Timothy Henrich of Brigham and Women's Hospital in Boston, Massachusetts, who discussed the cases at a meeting of the International AIDS Society in Kuala Lumpur, Malaysia, this week.

There is one previous case of an HIV-positive individual seemingly being cured following a bone marrow transplant, but the donor was HIV-resistant. Henrich's patients received bone marrow from ordinary donors, making their apparent recovery a puzzle.

"We need to understand better why these patients have undetectable virus," says Françoise Barré-Sinoussi of the Pasteur Institute in Paris, France, who was not involved in the study. Barré- Sinoussi, who shared a Nobel prize in 2008 for the co-discovery of HIV as the virus that causes AIDS, says studying the men could lead to new treatments that do not involve transplants.

Another option is simply to treat people with HIV earlier. Until this week, the WHO recommended that HIV treatment should begin when each millilitre of an infected person's blood contains fewer than 350 CD4 cells, the white blood cells targeted and destroyed by HIV. At the Malaysia meeting, it launched new guidelines recommending treating people as soon as their cell count drops to 500 per millilitre. This would raise the number of people eligible for treatment worldwide from 16.7 million to 26 million.

Philippa Easterbrook, an HIV specialist with the WHO, says the evidence behind the change in policy came from a WHO review of 24 studies, which shows that early treatment lowers the chances of both disease progression and transmission. "The evidence base was compelling," she says.

Earlier treatment appears to prevent spread by flushing the virus from the blood. Within three to six months of starting earlier treatment, 80 per cent of people with HIV have undetectable levels of virus in their blood.

"We all welcome these new guidelines to treat at the 500-cell cut-off," says Barré-Sinoussi. "We must work through national programmes, NGOs and communities in the field to apply these recommendations."

This article appeared in print under the headline "Double good news from HIV front line"

Source: http://www.newscientist.com/article/mg21929244.800-double-good-news-from-hiv-front- line.html#.Ud5xb_k3B6M

HIV patients apparently virus-free, off antiretroviral drugs

By Lena H. Sun and Brady Dennis, Published: July 4, 2013

Two HIV-infected men who had bone marrow transplants to treat their blood cancers have stopped taking their antiretroviral drugs and still show no sign of the virus, according to research released Wednesday that experts say represents significant developments in understanding the biology of the virus and the ongoing search for a cure.

The researchers from Brigham and Women’s Hospital in Boston told an international AIDS conference in Malaysia that one patient stopped taking his antiretroviral therapy 15 weeks ago as of Wednesday and the other, seven weeks ago.

60 In patients who stop taking medication, the virus comes back in two to four weeks. The researchers described the results as “exciting” but said they do not indicate that the men have been “cured.” Follow-up of at least one year is needed to understand the full impact, they said.

Nevertheless, AIDS experts said the findings are important because they suggest that under the right conditions, HIV could be eradicated.

“It’s a proof of concept that under certain circumstances, even though these were very unusual circumstances, that you could conceivably rid the body of HIV,” Anthony Fauci, director of the National Institute of Allergy and Infections Diseases at the National Institutes of Health, said in an interview. “The thing that needs to be figured out is how you can do it without putting the patient through such a risky experience. Whether that’s possible, we don’t know.”

He said the public shouldn’t misinterpret the advance as a “cure” for HIV, or human immunodeficiency virus.

“You’re talking about a highly specific, very special situation that’s not really practical for the millions and millions of people who are HIV-infected, who are on therapy and would like to get off therapy,” he said.

The Boston patients had “very serious complications” and needed “very dramatic” treatment, Fauci said. That included chemotherapy, followed by treatment to suppress the body’s immune system before performing a stem cell transplant. Such intense and risky treatments simply wouldn’t make sense for most HIV patients, he said. The current therapy — usually one pill a day that combines three antiretroviral drugs — is still considered the most effective treatment, as long as patients take their medication daily.

A true cure could be achievable, he said. But it would need to be a treatment that’s safe, scalable and less harmful than current therapies. “We have to make sure the cure isn’t worse than the disease,” he said.

Until now, researchers have been unable to replicate the success of Timothy Ray Brown, the “Berlin patient,” the first person reported to be cured of HIV. Brown had a stem cell transplant in 2007 to treat his leukemia, and two years later, he was reported by his German doctors to have been cured of HIV. Brown’s doctors used a donor who had a rare genetic mutation whose cells could not be infected with HIV.

But researchers thought it might be possible to achieve similar results with ordinary donor cells if the patients stayed on their antiretroviral regimen during the transplant and for a time afterward to protect new cells from being infected by the virus. The latest results suggest that it worked.

“It is clear that the degree to which HIV was cleared by the transplant is unprecedented,” Steven Deeks, an AIDS researcher at the University of California at San Francisco who was not involved in the study, said Wednesday in an e-mail.

Last summer, Timothy Henrich and Daniel Kuritzkes, physician-researchers in the Division of Infectious Diseases at Brigham and Women’s Hospital, announced that the virus was easily detected in both men before their transplants and became undetectable by eight months post-transplant. At the time, both remained on antiretroviral therapy. One transplant took place three years ago, and the other took place five years ago.

A spokesman for Brigham and Women’s said the patients asked not to be identified other than to say they were men who had lymphoma.

Since coming off antiretroviral therapy in the spring, the men have been monitored frequently and continue to have no detectable HIV DNA or RNA in their blood.

Deeks said the most obvious explanation is that the new transplanted immune system killed the patient’s original immune system, leading to loss of the infected cell population.

“We were sort of holding our breath,” said Christine Durand, an assistant professor of infectious diseases at the Johns Hopkins School of Medicine, referring to how long the Boston patients would show no sign of infection.

61 A bone marrow transplant typically takes a few hours, but it takes months and possibly years for the donor cells to kill and replace the host cells.

In the Boston patients, it is still possible that “there’s one infected cell left in the brain,” said Durand, who specializes in transplant infectious diseases.

Durand and a team of researchers have begun a similar study of HIV-infected patients who need bone marrow transplants to treat their blood cancers. The Hopkins researchers are keeping the patients on the antiretroviral medication.

“This will change the way bone marrow transplant doctors think about HIV medication during bone marrow transplants,” Durand said.

“This means HIV cure could be an immediate goal when [patients] undergo bone marrow transplant.”

Source: http://www.washingtonpost.com/national/health-science/hiv-patients-apparently-virus-free-off- antiretroviral-drugs/2013/07/03/51a66b14-e401-11e2-aef3-339619eab080_story.html

TRATAMIENTO | Conferencia Internacional

Un trasplante de médula podría haber eliminado el VIH en dos infectados  De momento, según el principal in vestigador, no se puede hablar de curación  Hay que seguir los casos de ambos pacientes al menos durante un año más

Agencias | Madrid Actualizado miércoles 03/07/2013 15:57 horas

Una terapia con células madre podría haber eliminado el VIH en dos personas infectadas por el virus, tal y como revela una investigación realizada por la Facultad de Medicina de Harvard y el Hospital

62 Brigham and Women de Boston (en EEUU) y que se acaba de presentar en la Conferencia de la Sociedad Internacional del Sida que se está celebrando en Malasia.

Así lo explica su autor principal y miembro de ambas instituciones,Timothy Henrich, que afirma que ninguno de los dos pacientes muestran signos de VIH después de haber parado su tratamiento antirretroviral.

Ambos pacientes padecían linfoma de Hodgkin y llevaban un largo periodo sometidos a un tratamiento antirretroviral. Uno de ellos recibió el trasplante hace cuatro años y medio, mientras que el otro lo recibió hace tres años.

Los dos continuaron con el tratamiento contra el sida, pero uno lo abandonó hace cuatro meses y el otro hace siete semanas. Entonces, el VIH, que antes del trasplante era fácilmente detectable en la sangre de los hombres, se volvió 'invisible'. Henrich explicó que las células del donante habrían sustituido a las de los pacientes.

De momento, advierte el especialista,no se puede hablar de curación. Es "demasiado pronto" para decir con certeza que el virus ha desaparecido de sus cuerpos por completo. No obstante, ambos llevan alejados del tratamiento antirretroviral entre 15 y 7 semanas, respectivamente.

"Un seguimiento de al menos un año será necesario para entender el impacto total de un trasplante de médula ósea en el virus del sida", manifestó el científico, que también es profesor en la Escuela Médica de Harvard.

Aunque Henrich expone que la terapia con células madre "no es una opción viable para su uso generalizado al ser muy cara", sí afirma que estos casos "pueden abrir nuevas vías para luchar contra la enfermedad". Precisamente, señala que ésta "afecta a unos 34 millones de personas en todo el mundo".

Además, sostiene que existe "diferencias importantes" entre estos dos enfermos y el caso de Timoteo Ray Brown 'el paciente de Berlín', que se convirtió en la primera persona curada de VIH tras recibir un trasplante de médula ósea para la leucemia en el año 2007.

Así, explica que este último recibió células madre de un donante con una mutación genética rara (con resistencia al virus), mientras que a los dos de Boston de les administraron células sin la mutación. De cualquier manera, lo que queda claro es que el virus "ya no es una sentencia de muerte", concluye Henrich.

Source: http://www.elmundo.es/elmundosalud/2013/07/03/hepatitissida/1372859825.html

El virus del Sida no reaparece en pacientes sin tratamiento

Dos pacientes estadounidenses lograron expulsar el virus tras un trasplante de médula Ahora, después de abandonar los antirretrovirales, el patógeno sigue sin asomar

CAROLINA GARCÍA Washington 3 JUL 2013 - 19:53

Hace casi dos años se anunció el caso de dos hombres infectados por el virus de la inmunodeficiencia humana (VIH) que habían eliminado el patógeno de su cuerpo después de someterse a un trasplante de médula para tratarse la leucemia que padecían. Era la tercera vez que se registraba algo similar tras el famoso paciente de Berlin, el primero en conseguirlo.

Entonces se comunicó que ambos estaban libres del VIH aunque seguían sometiéndose al tratamiento antiviral por prevención. Ahora, investigadores presentes en el congreso

63 internacional sobre el Sida que se celebra en Malasia, han trasladado que, una vez retirada la medicación que mantiene a raya el virus, el VIH sigue sin aparecer, informa la agencia AP.

Ninguno de los dos pacientes está recibiendo tratamiento para combatir el VIH desde hace semanas, explicó en un comunicado Timothy Henrich, autor del estudio y médico en Harvard. Los casos forman parte de una investigación realizada por la Facultad de Medicina de Harvard y Hospital Brigham and Women, de Boston. Las identidades de los pacientes han sido mantenidas en secreto; uno de ellos recibió el trasplante hace cuatro años y medio y, el otro, lo recibió hace tres.

Al comienzo de la investigación eran tres los sujetos a estudio pero uno falleció en 2010, tras enfrentar una recidiva del cáncer. Desde que les realizaron los trasplantes los médicos no han encontrado ningún rastro de infección, aunque no se atreven a definir lo ocurrido como “curación”, ya que ha transcurrido muy poco tiempo desde que suspendieron el tratamiento con antirretrovirales. Uno de ellos lleva 15 semanas sin esta terapia y, el otro, siete.

La terapia basada en un trasplante de médula no es viable debido a los riesgos de esta intervención tan delicada

Los casos se presentaron por vez primera en julio de 2012 en el Congreso Internacional del sida (AIDS 2012) que tuvo lugar en Washington; los pacientes no presentaban ningún rastro de VIH en sangre después de su tratamiento con células madre adultas, pero ambos seguían con tratamiento antiviral. “Antes de la operación, el VIH era fácilmente detectable en la sangre de ambos pacientes, después se volvió invisible”, continúa Henrich en el comunicado.

A pesar de estos buenos resultados, la terapia basada en un trasplante de médula no parece una solución viable debido, fundamentalmente, a los riesgos de esta intervención tan delicada. Pero puede abrir una nueva vía para combatir la infección que afecta a unos 34 millones de personas en el mundo, según los últimos datos de la Organización Mundial de la Salud.

Los casos de los dos pacientes de Boston son similares al de Timothy Brown, conocido como el Paciente Berlín, que se convirtió en la primera persona en la que quedó científicamente probado que se curó del VIH tras recibir un trasplante de médula ósea por padecer una leucemia en el año 2007.

Aunque son diferentes en el fondo. En el caso de Brown, los médicos utilizaron células madre de un donante con una rara mutación genética, conocida como la CCR5 delta 32, que hace a las personas resistentes al VIH (inhabilita una de las puertas de entrada del VIH). Los enfermos de Boston recibieron células madre sin esta mutación.“El doctor Henrich está dibujando un nuevo territorio en la investigación para la erradicación del VIH”, explicó en un comunicado Kevin Frost, director ejecutivo de la Fundación para la Investigación del Sida, que financió el estudio.

Los avances científicos que se han sucedido desde que fuera descubierto el VIH hace ya 30 años han demostrado que la infección no es una sentencia de muerte. Los antirretrovirales más recientes para combatir el sida mantienen a raya la enfermedad durante décadas. Algunos

64 estudios incluso concluyen en que la esperanza de vida de las personas con VIH sometidas a tratamiento es casi la misma que aquellas personas que no están infectadas.

A pesar de los avances, todavía hay miles de personas en el mundo que no tienen acceso al tratamiento, según datos de la OMS. “Lo que hay que conseguir es acelerar el proceso de tratamiento que debería empezar justo en el momento en que una persona de positivo para la enfermedad”, informan desde este organismo.

Source: http://sociedad.elpais.com/sociedad/2013/07/03/actualidad/1372874019_733150.html

Two Patients HIV-Free After Stem Cell Treatment Published: Jul 3, 2013 | Updated: Jul 3, 2013

By Michael Smith , North American Correspondent, MedPage Today Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

65  Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.  Note that researchers have demonstrated that two men with HIV who received a bone marrow transplant were able to stop anti-retroviral therapy without viral rebound.  Be aware that bone marrow transplant is too risky a strategy to broadly employ in the treatment of HIV.

KUALA LUMPUR -- Two HIV-positive men who got a stem cell transplant to treat blood cancers have now been off antiretroviral drugs for several weeks without evidence of the virus rebounding, a researcher said here.

The apparent HIV remissions are exciting developments, but it is too early to say the men have been cured, according to Timothy Henrich, MD, of Brigham and Women's Hospital in Boston.

"It is possible that the virus could come back next week," Henrich told reporters before his late-breaker presentation at the 7th International AIDS Society meeting on HIV pathogenesis, treatment, and prevention.

But researchers have been unable to find evidence of HIV replication or of HIV DNA integrated into inactive immune cells, although the men have been off HIV therapy for 8 and 15 weeks, respectively, Henrich reported.

If that state persists, he said, it might offer clues to a more widely applicable approach to inducing HIV remission, since stem cell transplant is "not a practical strategy" to cure the 34 million people with HIV worldwide.

Outside experts also cautioned against hyping the findings.

"The next step is to confirm this in larger numbers," said Sharon Lewin, MD, of Monash University in Melbourne, Australia. That might be possible because stem cell transplants are performed relatively often around the world, some of them in people with HIV.

But she echoed Henrich's view that stem cell transplant will not be widely useful in curing HIV, if only because of the expense and risk of the procedure.

But, she told reporters, such cases are "absolutely instrumental in moving the science forward."

Indeed, Henrich said, so far investigators don't know what aspect of the stem cell transplant and subsequent therapy led to the disappearance of the virus.

The best guess at the moment, Henrich said, is that graft-versus-host disease -- a common sequel to allogeneic stem cell transplant -- eliminated HIV-bearing host cells while the donor cells were protected from infection by antiretroviral therapy.

The finding is reminiscent of the case of Timothy Brown, the "Berlin patient," who was the first person to have an apparently curative stem cell transplant.

But in that case, doctors sought a donor whose immune cells carried a mutation -- the delta32 variant of the CCR5 gene -- that rendered them resistant to HIV infection.

Brown had what is called myoablative conditioning to completely destroy his own immune system before getting the donor cells and was not on antiretroviral drugs after the transplant.

In the two cases in Boston, both men had minimal conditioning with chemotherapeutic drugs, so their own immune systems were not completely destroyed. And they got donor cells that -- in principle -- were susceptible to HIV.

66 During and after the transplant, both patients remained on antiretroviral therapy for 2.7 and 4.5 years of follow- up before stopping therapy, Henrich said.

It was only recently -- after consultation with ethics boards, the patients themselves, and their doctors -- that Henrich and colleagues "felt justified" in stopping the anti-HIV medications.

The decision to undertake an "analytical treatment interruption" was based on the continuing inability to find HIV in the two men, Henrich said.

Because of the effectiveness of current anti-HIV therapy, the investigators thought stopping treatment entailed "minimal risk" to the patients, senior investigator Dan Kuritzkes, MD, also of Brigham and Women's, told MedPage Today.

Such treatment interruptions have been tested several times in patients who have suppressed virus under antiretroviral therapy, and usually result in HIV rebound within days.

But there are several cases -- including a cohort in France -- where such interruptions have led to durable control of the virus without the need to resume anti-HIV therapy.

And U.S. researchers are following up the case of an HIV-positive infant, treated within hours of birth, who currently has no evidence of the virus although she was lost to follow-up and did not receive treatment for several months.

In the months and years to come, Lewin said, it's extremely likely that more such individual cases of HIV remission will be found, which might raise "false hope" for a cure.

"We want a much larger, scalable cure" to treat 34 million people, she said, "and that is going to be quite a challenge."

Primary source: International AIDS Society Source reference: Henrich T, et al. "In depth investigation of peripheral and gut HIV-1 reservoirs, HIV-specific cellular immunity, and host microchimerism following allogeneic hematopoetic stem cell transplantation" IAS 2013; Abstract WELBA05.

Source: http://www.medpagetoday.com/meetingcoverage/ias/40254

Closer To An HIV Cure? No Trace Of Virus After 2 Men Underwent Stem Cell Transplants

Posted: 07/03/2013 10:01 am EDT

67 After undergoing stem cell transplants as treatment for cancer, two patients with HIV now have no trace of the virus in their systems and haven't required their HIV medication for several weeks, doctors reported today.

However, doctors cautioned that it's still too soon to say that the patients have been definitively cured, as they have only been off their treatments for 15 weeks and seven weeks, respectively.

The research, led by Dr. Timothy Henrich of Harvard Medical School and Brigham and Women’s Hospital in Boston, reported the findings today at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

"They are doing very well," Henrich said at the conference, as reported by the Associated Press. "While these results are exciting, they do not yet indicate that the men have been cured. Only time will tell."

The two patients had been HIV positive and had been taking antiretroviral medication for their condition. However, they each developed Hodgkin’s lymphoma (one patient reportedly had other blood cancers as well) and so underwent chemotherapy as well as stem cell transplants while still receiving their antiretroviral medications. The Los Angeles Times reported that the men received their transplants at different times; one four- and-a-half years ago, and the other nearly three years ago. After undergoing the stem cell transplants, the virus is now undetectable.

However, the Associated Press reported that more time is needed to determine if the HIV virus isn't just hiding undetected elsewhere in the body. Dr. Robert Siciliano of Johns Hopkins University explained in a statement that it may take more than a year to make sure viral rebound does not occur, and that doctors will have to continue monitoring the patients.

The first news of these two men came last year at the 2012 International AIDS Conference; back then, they had undetectable HIV levels in their blood plasma, but had not yet been taken off antiretroviral medications.

The approach Henrich and his team have taken is similar to that of Timothy Brown, also known as the "Berlin Patient," who underwent stem cell transplantation as part of his treatment protocol for leukemia, before being the first person deemed "cured" of HIV. However, in Brown's case, the stem cells transplanted into him were HIV- resistant stem cells, while in the cases of these two men, the stem cells did not have that genetic mutation for HIV resistance. Brown also received a more intensive chemotherapy regimen.

The Los Angeles Times reported that this method -- stem cell transplantation -- is likely to be unfeasible for most HIV-positive people. NBC News pointed out last year that the reason why the approach seemed to work for these men is because they had certain gene mutations that made their immune system cells resistant to HIV infection, and that in general, bone marrow transplants are expensive procedures with a 15 percent fatality rate.

This is just one of the latest HIV treatment breakthroughs that have been reported as of late. Earlier this year, a baby born with HIV was considered "functionally cured," the Associated Press reported. That baby was born to a mother with HIV. The baby was given faster, stronger-than-usual treatment immediately upon birth, even before doctors were able to test that the baby actually was infected with HIV. At the time of the reporting of this news, the child was 2.5 years old and hadn't needed to take antiretroviral medication for a year.

And just after the news of this baby was reported, researchers from France reported the "functional cure" of 14 adults with HIV, who were treated extremely early with combination antiretroviral therapy (cART). Now, their HIV levels are barely detectable, and they have been able to stop taking their treatment.

Source: http://www.huffingtonpost.com/2013/07/03/2-men-cured-of-hiv-lymphoma-stem-cell- transplant_n_3540295.html

Can stem-cell transplants eliminate HIV? Doctors report that a cancer-fighting technique helped wipe out the virus in two Boston men By Chris Gayomali | July 3, 2013

Timothy Henrich is the leader of a new study revealing a "cure" for the HIV virus. AP Photo/Lai Seng Sin

Timothy Brown shocked the world in 2011 when his doctors announced that the HIV virus he had been carrying since 1995 had miraculously disappeared. The "Berlin patient," as he came to be known, was the recipient of a

69 life-saving stem-cell transplant from a bone marrow donor, a procedure that was used to treat Brown for leukemia. And with that, doctors suspected that they had stumbled upon a cure for HIV.

In efforts to duplicate Brown's success, Dr. Timothy Henrich of Brigham and Women's Hospital and Harvard Medical School in Boston set out to find HIV patients with either leukemia or lymphoma. The initial results were first announced at an international AIDS conference last July, when Henrich and his colleagues reported that two Boston men with lymphoma, who did not wish to have their names revealed to the public, had flushed the virus from their bodies after undergoing stem-cell transplants to replace their ravaged bone marrow.

Doctors just announced that the patients, who were on long-term drug therapy to treat their HIV, still possessed undetectable levels of the virus in their blood several months after undergoing the procedure.

"We looked very deeply this time — much more deeply than last time," Henrich told NBC News. Researchers examined the immune system cells that HIV attacks (particularly the CD4 and CD8 T-cells), and samples in the patients' rectal tissue for evidence of the virus, but came up empty. "We don't even know where some of the HIV might be hiding," said Henrich.

In Brown's instance, doctors used stem cells possessing a rare genetic mutation called CC45 delta 32, which is typically found in people resistant to the HIV virus. The two Boston patients, however, received stem cells from donors without this mutation. According to Nature, it could be "that an immune response called graft-versus-host disease — a post-transplant reaction in which donated cells kill off a patient's own cells — may have then wiped out the patients' HIV reservoirs, potentially curing the men."

However, doctors are hesitant to pronounce either case a resounding "cure."

"There never is an 'aha' moment when you suddenly can declare a cure," said Kevin Robert Frost, CEO of the Foundation for AIDS Research (amFAR), which helped pay for the study. "It is impossible to prove the absence of something." That said, stem-cell transplants from an unrelated donor are risky and expensive: In Brown's case $250,000. As New York noted in a 2011 profile on the Berlin patient, the procedure is "a reasonable risk only in the face of imminent death."

Source: http://theweek.com/article/index/246441/can-stem-cell-transplants-eliminate-hiv

Two Patients Rid of HIV?

Bone marrow transplants appear to have eliminated HIV from Boston cancer patients.

By Kate Yandell | July 3, 2013 Electron micrograph of a T cell infected with

HIVFLICKR, NIAIDTimothy Ray Brown, the “Berlin patient,” was the first person reported to be cured of HIV. He has shown no signs of infection for five years since receiving a bone marrow transplant to treat leukemia. Now doctors are reporting that two more patients show no signs of HIV after receiving bone marrow transplants as treatment for lymphoma.

The two men received the transplants several years ago at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, researchers said at the AIDS Society Conference in Koala Lumpur today (July 3). Throughout the transplants and the recovery, the patients took anti-retroviral medication. But following extensive testing,

70 they both recently went off their AIDS medicines. One of the patients has remained free of signs of HIV for the last seven weeks, while the other has remained HIV-free in the 15 weeks since he went off his medication.

“While these results are exciting, they do not yet indicate that the men have been cured,” said Timothy Henrich, one of the Brigham and Women’s Hospital doctors who treated the patients, according to The Guardian. “Long- term follow up of at least one year will be required to understand the full impact of a bone marrow transplant on HIV persistence.”

“These findings clearly provide important new information that might well alter the current thinking about HIV and gene therapy,” Foundation for AIDS Research head Kevin Frost told BBC News. “While stem-cell transplantation is not a viable option for people with HIV on a broad scale because of its costs and complexity, these new cases could lead us to new approaches to treating, and ultimately even eradicating, HIV.”

The transplants given to the Boston patients were a bit different from the transplant that Brown, the Berlin patient, received. Brown was given bone marrow from a donor who had a rare mutation that confers resistance to HIV, but Brown did not receive anti-retroviral therapy throughout the transplant process, The New York Times explained. The Boston patients received transplants from ordinary donors without the anti-HIV mutation and remained on AIDS medications throughout the transplant process and afterwards. It is encouraging that the Boston transplants appear to have been effective, since it indicates that finding rare bone marrow donors with the anti-AIDS mutation might not be necessary for eradicating the disease.

Still, the treatment is too dangerous to be attempted on ordinary HIV patients who do not also have life- threatening cancer. The type of bone marrow transplant that the Boston men received carries a 15 percent risk of death.

Doctors believe that the treatment was effective because the patients took anti-retroviral therapy in conjunction with the bone marrow transplant. HIV often hides in bone marrow cells. Researchers speculate that once the transplanted bone marrow cells replaced the patients’ original cells, the anti-retroviral drugs kept the new cells from becoming infected. Meanwhile, the transplanted cells were killing off the patients’ original HIV-infected cells in a phenomenon called graft-versus-host disease, eliminating the disease’s reservoir from the body.

It remains to be seen whether the HIV could still be hiding somewhere in the two Boston patients’ body, such as in the brain or the gut, Henrich said.

Source: http://www.the-scientist.com/?articles.view/articleNo/36333/title/Two-Patients-Rid-of-HIV

EUROPAIKOS NOTOS

ÐÝìðôç, 4 Éïõëßïõ 2013

Με μεταμόσχευση μυελού των οστών νίκησαν το AIDS

Η είδηση που αναδημοσιεύει και το BBC και κάνει τον γύρο του κόσμου, γεμίζει αισιοδοξία για άλλη μια νίκη απέναντι στο

71 AIDS. Μια νίκη που ίσως στο μέλλον ανοίξει νέους δρόμους στην καταπολέμηση του ιού. Δύο άνδρες με AIDS, ύστερα από μεταμόσχευση του μυελού των οστών, στην οποία υποβλήθηκαν δεν παρουσιάζουν πλέον τον ιό HIV στο αίμα τους. Οι διαπιστώσεις για το τι συνέβη παρουσιάστηκαν στο International Aids Society Conference και είναι οι εξής: Δυο ασθενείς με AIDS που ήταν φορείς για 30 χρόνια και κρατούσαν τον ιό σε ύπνωση με αντιρετροϊκά φάρμακα, νόσησαν και μετά από λίγο καιρό εμφάνισαν λέμφωμα (καρκίνο). Οι γιατροί για να τον αντιμετωπίσουν αναγκάστηκαν να τους κάνουν μεταμόσχευση μυελού. Λίγο μετά την μεταμόσχευση ο HIV, είχε εξαφανιστεί από το αίμα τους. Όμως παρά την απρόσμενη αυτή επιτυχία (τον καρκίνο ήθελαν οι γιατροί να καταπολεμήσουν) η επιστημονική κοινότητα είναι ακόμη συγκρατημένη, διότι αυτό έγινε σε ασθενείς με καρκίνο. Η ομάδα του νοσοκομείου Brigham στις ΗΠΑ που έκανε την μεταμόσχευση τόνισε ότι: "είναι πολύ νωρίς για να μιλήσουμε για μια θεραπεία, όπως ο ιός θα μπορούσε να επιστρέψει οποιαδήποτε στιγμή." Πάντως οι 2 άνδρες ζουν εδώ και 4 μήνες δίχως να έχουν λάβει κάποια φαρμακευτική αγωγή. Ο Dr Timothy Henrich δήλωσε στο BBC ότι τα αποτελέσματα ήταν συναρπαστικά. Αλλά διευκρίνισε: «Εμείς δεν μιλάμε ακόμη για θεραπεία. Είναι δύσκολο να απαλλαγούμε από τη μόλυνση με HIV, γιατί κρύβει μέσα του, ανθρώπινο DNA. Ο μυελός των οστών είναι το σημείο όπου δημιουργούνται νέα κύτταρα του αίματος και πιστεύουμε ότι είναι μια σημαντική δεξαμενή για τον HIV. Η μεταμόσχευση που έγινε για άλλο λόγο ίσως να ανοίξει νέους δρόμους". iatropedia.com

Source: http://europaikosnotos.blogspot.in/2013/07/aids.html

The Lancet Infectious Diseases, Volume 13, Issue 8, Pages 660 - 661, August 2013 doi:10.1016/S1473-3099(13)70158-0Cite or Link Using DOI Published Online: 03 July 2013 Copyright © 2013 Published by Elsevier Ltd. All rights reserved. Patients have undetectable HIV after coming off treatment Peter Hayward Two patients with HIV who received haemopoietic stem cell transplants have no detectable virus in blood samples up to 15 weeks after treatment interruption. Just don't say “cured”, Peter Hayward reports. At the World Aids Conference 2012 (Washington, DC, USA), Timothy Henrich and Daniel Kuritzkes of Brigham and Women's Hospital (Boston, MA, USA) reported that two men with longstanding HIV infections had no detectable virus in blood or lymphocytes, but at that point the men remained on antiretrovi ...

72 Source: http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(13)70158-0/fulltext

Nature news Stem-cell transplants may purge HIV

But treatment is too risky for most people infected by the virus.

Erika Check Hayden 03 July 2013

International AIDS Society/Steve Forrest/Workers' Photos

Daniel Kuritzkes, a researcher working with two 'Boston patients' who may have been cured of HIV, speaks at an AIDS conference in Kuala Lumpur, Malaysia.

Two men with HIV may have been cured after they received stem-cell transplants to treat the blood cancer lymphoma, their doctors announced today at the International AIDS Society Conference in Kuala Lumpur.

One of the men received stem-cell transplants to replace his blood-cell-producing bone marrow about three years ago, and the other five years ago. Their regimens were similar to one used on Timothy Ray Brown, the 'Berlin patient' who has been living HIV-free for six years and is the only adult to have been declared cured of HIV. Last July, doctors announced that the two men — the ‘Boston patients’ — appeared to be living without detectable levels of HIV in their blood, but they were still taking antiretroviral medications at that time.

Timothy Henrich, an HIV specialist at Brigham and Women’s Hospital in Boston, Massachusetts, who helped to treat the men, says that they have now stopped their antiretroviral treatments with no ill effects. One has been off medication for 15 weeks and the other for seven. Neither has any trace of HIV DNA or RNA in his blood, Henrich says.

If the men stay healthy, they would be the third and fourth patients ever to be cured of HIV, after Brown and a baby in Mississippi who received antiretroviral therapy soon after birth.

But Henrich and Daniel Kuritzkes, a colleague at Brigham who also worked with the men, caution that it is still too early know whether or not the Boston patients have been cured. For that, doctors will need to follow the men closely for at least a year, because the virus may be hiding out in 'reservoirs' — parts of the men’s bodies, such as their brain or gut, that can harbour the virus for decades.

“We’re being very careful not to say that these patients are cured,” Kuritzkes says. “But the findings to date are very encouraging.”

HIV researcher Steven Deeks of the University of California, San Francisco, says that doctors might need to wait at least two years before declaring that a cure has been achieved. “Any evidence that we might be able to cure HIV infection remains a major advance,” Deeks says. But, he adds, “there have been cases of patients who took many weeks off therapy before the virus took off”. Exciting news

74 Still, researchers and doctors are excited about the news, especially because the Boston patients’ treatment differed from the Berlin patient’s regimen in one key way. Brown was given stem cells that were predisposed to resist HIV infection, because the donor happened to have a mutated version of a key protein — CCR5 — that is needed for HIV to infect cells. So Brown’s transplant was akin to gene therapy with HIV-resistant cells.

But the Boston patients received stem cells without the protective mutation. The transplanted cells must therefore have been protected from infection by the antiretroviral drugs taken during cancer treatment. Their doctors think that an immune response called graft-versus-host disease — a post-transplant reaction in which donated cells kill off a patient’s own cells — may have then wiped out the patients’ HIV reservoirs, potentially curing the men.

Transplant specialist Christine Durand of Johns Hopkins University School of Medicine in Baltimore, Maryland, says that the case of the Boston patients may show that current antiretroviral drugs are powerful enough, on their own, to protect the transplanted cells. “If cure has been achieved in the Boston patients, then it was the antiretroviral therapy, not gene therapy, that protected the donor cells,” she says.

The finding is very important for people with HIV who also need blood-cell transplants, but the treatment is unlikely to be used more generally because the risks from transplants are high. Durand says that Johns Hopkins is now revising its transplant procedures to keep people with both cancer and HIV on antiretroviral drugs during the transplant regimen.

Separately, the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, based in Silver Spring, Maryland, is trying to replicate the Berlin patient’s cure by giving CCR5-mutated HIV-resistant blood from umbilical cords to children and adults with HIV and cancer.

Everyone with HIV could benefit from this work, researchers say, because it could yield valuable information about how to eliminate the HIV reservoir.

“We are still a long way off from a viable cure option for most patients,” Durand says. “But every step counts, and these cases can teach us important lessons.”

Nature doi:10.1038/nature.2013.13297

Source: http://www.nature.com/news/stem-cell-transplants-may-purge-hiv-1.13297

HIV Treatment > Search for a Cure IAS 2013: Boston Stem Cell Transplant Recipients Now Controlling HIV Off Treatment

Details Category: Search for a Cure Published on Wednesday, 03 July 2013 00:00 Written by Keith Alcorn

Timothy Henrich (Photo: Liz Highleyman)

75 Two people with HIV who received stem cell transplants to treat lymphoma are now controlling HIV replication without antiretroviral medication in the early weeks of treatment interruption, following the discovery that both had experienced loss of detectable HIV DNA, researchers from Boston reported Wednesday at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) in Kuala Lumpur.

[Produced in collaboration with Aidsmap.com]

Although the treatment patterns of the 2 patients bear some similarities to the Berlin Patient, who experienced a "functional cure" of HIV infection after aggressive chemotherapy, immunosuppressive treatment, and a bone marrow transplant from a donor with genetic resistance to HIV, the Boston patients also differ in several respects, which could provide important clues about how remission from active HIV infection could be achieved in other people with long-standing HIV infection.

The findings were reported by Timothy Henrich of Brigham and Women’s Hospital in Boston, who has led the team conducting extensive tests on the patients. The analysis involves a small group of patients with HIV who were evaluated after allogeneic hematopoietic stem cell transplants for lymphoma at hospitals in Boston (transfer of stem cells that will replace all blood cells, derived from genetically matched donors). Although 3 patients were originally evaluated, 1 died of recurrent Hodgkin lymphoma 6 months after the transplant.

Both surviving patients had been receiving prolonged antiretroviral therapy (ART) and received stem cell transplants with a reduced-intensity conditioning regimen of chemotherapy designed to eradicate the cancer and eliminate existing bone marrow cells. The conditioning regimen did not include radiotherapy and it did not eliminate the residual lymphocyte population. In contrast, the Berlin Patient received a much more aggressive regimen which eliminated existing bone marrow cells.

The current transplants also differed from the Berlin Patient because they did not come from donors with genetic resistance to HIV infection (CCR5-delta-32 mutation), so the cells were susceptible to HIV infection.

Measurements of HIV DNA showed that around 200 days after transplantation HIV DNA levels had declined below 50 log copies per million peripheral blood mononuclear cells (PBMCs) in one patient, while HIV DNA fell below this level around 280 days after transplant in the other patient. In both cases HIV DNA levels have continued to decline after this point. They have now been followed after transplantation for 21 months (Patient A) and 42 (Patient B).

More sensitive HIV DNA testing using larger samples of blood obtained by leukapheresis, and rectal tissue biopsy showed that HIV DNA was below the limit of detection in both patients. Patient A provided a sample of 25 million PBMCs, and testing with a limit of detection of 0.07 copies per million PBMCs failed to detect HIV DNA. Patient B provided a sample of 50 million PBMCs, and testing with a limit of detection of 0.01 international units per million PBMCs similarly failed to detect HIV DNA.

Viral co-culture from CD4 lymphocytes failed to detect HIV in either patient. A rectal biopsy from Patient B failed to detect HIV DNA in rectal cells that would be expected to provide a reservoir for HIV (limit of detection 2 copies per million cells).

After establishing that HIV DNA could not be detected, the researchers conducted extensive discussions with the patients and healthcare providers over a 6-month period about the acceptability of an experimental or analytic treatment interruption in order to test viral control off antiretroviral medication.

Both patients consented after review of the study protocol by an internal review board. The patients are now being intensively monitored with weekly viral load (HIV RNA) tests and bi-weekly testing of HIV DNA in

76 PBMCs, and after 6-8 weeks the patients gave large volumes of blood for more sensitive analysis of HIV DNA. Leukapheresis will be repeated every 3 months.

To date, Patient A has been off treatment for 7 weeks and Patient B for 15 weeks. Neither patient has yet shown any evidence of viral replication by RNA testing or any evidence of HIV DNA in PBMCs. Week 6 testing of larger blood samples from Patient B has similarly failed to detect HIV. Neither transplant recipient showed any evidence of HIV-specific immune responses.

Henrich told reporters that the research group believes the substantial reduction in the viral reservoir to be a consequence of a post-transplant graft-versus-host reaction.

"This graft-versus-host effect clears out the residual host cells," he said. "For 6 to 9 months after the reduced intensity conditioning transplant we see a mingling of the donor and host cells, and what happens over time is that the donor cells clear out the host cells."

"The peripheral blood lymphocytes that it clears out are a major reservoir for HIV," he continued. "What we think is happening is that there is a non-specific clearing by the donor cells which recognize the host cells as being just a little bit different."

Testing carried out around 200 days after the transplants showed that in both patients, host cells had been almost entirely replaced by donor-derived PBMCs; only 0.00041%-0.00081% of PBMCs were still host-derived in one patient, and the distribution was almost identical in the other patient.

Donor cells seem to be protected "by the fact that we kept them on antiretroviral therapy during and after transplantation while the residual reservoir was decaying and the new donor cells were taking over," said Henrich.

The researchers are careful not to describe their findings as a functional cure. Dan Kuritzkes of Brigham and Women’s Hospital and Harvard Medical School, also a member of the research group, commented that previous studies of structured treatment interruption showed that the majority of patients experienced viral rebound within 2 to 4 weeks, virtually everyone was viremic by week 8, and most reached a plateau in viral rebound by weeks 12-16. "In each study, 1 or 2 patients tend to lag behind the others, so that’s why we’re being careful," he said.

Researchers do not rule out the re-emergence of virus replication even after a year, which is why intensive sampling will continue for the foreseeable future.

"This is not a practical strategy that we can do for most people with HIV," Henrich told reporters. "Stem cell transplantation is dangerous. There can be up to 20% mortality associated with stem cell transfer in the first year after transplantation."

The chief value of the study will be in what it tells researchers about the reductions in HIV DNA that might need to be achieved in order to control HIV off treatment, Henrich concluded.

"How low do we need to go -- what level of reduction of the reservoir do you need in order to achieve a lasting impact?" he asked. "We hope our study will shed light on this important question."

See also: IAS 2013: Stem Cell Transplant Patients Remain HIV-Free [VIDEO]

7/3/13

Reference

T Henrich, E Hanhauser, M Sirignano, D Kuritzkes, et al. In depth investigation of peripheral and gut HIV-1 reservoirs, HIV-specific cellular immunity, and host microchimerism following allogeneic hematopoetic stem cell transplantation. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract WELBA05.

77 Source: http://www.hivandhepatitis.com/hiv-treatment/hiv-cure/4178-ias-2013-boston-stem-cell-transplant- recipients-now-controlling-hiv-off-treatment

IAS 2013: Stem Cell Transplant Patients Remain HIV-Free [VIDEO]

Category: Search for a Cure Published on Wednesday, 03 July 2013 00:00 Written by Gregory Fowler Timothy Henrich (Photo: Liz Highleyman)

Two Boston men with HIV who received bone marrow transplants after a milder conditioning chemotherapy regimen continued to have undetectable virus 7 and 15 weeks after undergoing experimental treatment interruption, researchers reported at the 7th International AIDS Society Conference on HIV Pathogenesis,

78 Treatment and Prevention (IAS 2013) this week in Kuala Lumpur.

As reported at last year's International AIDS Conference, the men underwent allogeneic stem cell transplants to treat lymphoma. Unlike the Berlin Patient, the donors' stem cells were susceptible to HIV infection (not CCR5- delta-32) and the patients stayed on antiretroviral therapy (ART) throughout the transplant process.

VIDEO: HIV-FREE AFTER STEM CELL TRANSPLANTS http://youtu.be/QyemOzWj27U

[Timothy Henrich speaks at IAS 2013 press conference, Kuala Lumpur, July 2, 2013]

After HIV fell to very low levels in their blood and gut tissue, the patients underwent analytic ART interruption with frequent and careful monitoring. To date, according to Timothy Henrich from Brigham and Women's Hospital, HIV RNA remains undetectable in peripheral blood and integrated HIV DNA cannot be detected in cells.

Henrich described these patients at a press conference prior to his late-breaker presentation at the final session of the conference. He stressed that we do not yet understand the mechanisms responsible for these findings, and it is too soon to declare that these individuals are functionally cured.

See also: IAS 2013: Boston Stem Cell Transplant Recipients Now Controlling HIV Off Treatment

7/3/13

Reference T Henrich, E Hanhauser, M Sirignano, D Kuritzkes, et al. In depth investigation of peripheral and gut HIV-1 reservoirs, HIV-specific cellular immunity, and host microchimerism following allogeneic hematopoetic stem cell transplantation. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract WELBA05.

Source: http://www.hivandhepatitis.com/hiv-treatment/hiv-cure/4176-ias-2013-stem-cell-transplant-patients- remain-hiv-free-video

Two stem cell transplant recipients now controlling HIV off treatment Transplanted cells may have cleared out HIV-infected cells in graft versus host reaction

Keith Alcorn Published: 03 July 2013 Timothy Henrich of Brigham and Women’s Hospital, Boston, speaking at IAS 2013. Photo ©International AIDS Society/Marcus Rose/Workers' Photos

Two people with HIV who received stem cell transplants for the treatment of lymphoma are now controlling HIV replication without medication in the early weeks of treatment interruption, following the discovery that both had experienced loss of detectable HIV DNA,

researchers from Boston reported on Wednesday at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.

79 Although the treatment patterns of the two patients bear some similarities to the 'Berlin patient' – who experienced a 'functional cure' of HIV infection after aggressive chemotherapy, immunosuppressive treatment and a bone marrow transplant from a donor with genetic resistance to HIV – the 'Boston patients' also differ in several respects, which could provide important clues about how remission from active HIV infection could be achieved in other people with longstanding HIV infection.

"This is not a practical strategy that we can do for most people with HIV. Stem cell transplantation is dangerous." Dr Timothy Henrich

The findings were reported by Timothy Henrich of Brigham and Women’s Hospital, Boston, who has led the team conducting extensive tests on the patients. They concern a small group of people with HIV who were evaluated after hematopoietic stem cell transplants for lymphoma at hospitals in Boston (transfer of stem cells that will replace all blood cells, derived the from genetically matched donors). Three patients were originally evaluated but one died of recurrent Hodgkin's lymphoma six months after the transplant.

Both the surviving patients had been receiving prolonged antiretroviral therapy and received stem cell transplants with a reduced-intensity conditioning regimen of chemotherapy designed to eradicate the cancer and eliminate the existing bone marrow. In the case of the two patients under investigation, the conditioning regimen did not include radiotherapy and it did not eliminate the residual lymphocyte population. In contrast, the 'Berlin patient' received a much more aggressive regimen which eliminated existing bone marrow cells.

The transplants also differed from the 'Berlin patient' because they did not come from donors with genetic resistance to HIV infection (a CCR5 delta 32 mutation), so the cells were susceptible to HIV infection.

Measurements of HIV DNA showed that, around 200 days after transplant, HIV DNA levels had declined below 50 log copies per million PBMCs (peripheral blood mononuclear cells, part of the immune system) in one patient, while HIV DNA fell below this level around 280 days after transplant in the other patient. In both cases, HIV DNA levels have continued to decline after this point. After transplantation, the two patients have been followed for 21 (patient A) and 42 months (patient B), respectively.

More sensitive HIV DNA testing using larger samples of blood obtained by leukapheresis and rectal tissue biopsy showed that HIV DNA was below the limit of detection in both patients. Patient A provided a sample of 25 million

PBMCs, and testing with a limit of detection of 0.07 copies per million PBMCs failed to detect HIV DNA. Patient B provided a sample of 50 million PBMCs, and testing with a limit of detection of 0.01 international units per million PBMCs similarly failed to detect HIV DNA.

Viral co-culture from CD4 lymphocytes failed to detect HIV in either patient. A rectal biopsy in patient B failed to detect HIV DNA in rectal cells that would be expected to provide a reservoir for HIV (limit of detection 2 copies per million cells).

80 After establishing that HIV DNA could not be detected, the researchers conducted extensive discussions with the patients and healthcare providers over a six-month period about the acceptability of an experimental treatment interruption in order to test viral control off medication.

Both patients consented after review of the study protocol by an internal review board. The patients are now being intensively monitored with weekly viral load (RNA) tests and bi-weekly testing of HIV DNA in PBMCs and, after six to eight weeks, the patients gave large volumes of blood for more sensitive analysis of HIV DNA. Leukapheresis will be repeated every three months.

To date, Patient A has been off treatment for seven weeks and Patient B for 15 weeks. Neither patient has yet shown any evidence of viral replication by RNA testing or any evidence of HIV DNA in PBMCs. Week-six testing of larger blood samples from Patient B has similarly failed to detect HIV.

Neither transplant recipient showed any evidence of HIV-specific immune responses.

Timothy Henrich told reporters that the research group believes the substantial reduction in the viral reservoir to be a consequence of a post-transplant graft-versus-host reaction.

“This graft-versus-host effect clears out the residual host cells,” he said. “For six to nine months after the reduced intensity conditioning transplant, we see a mingling of the donor and host cells, and what happens over time is that the donor cells clear out the host cells. The peripheral blood lymphocytes that it clears out are a major reservoir for HIV. What we think is happening is that there is a non-specific clearing by the donor cells which recognise the host cells as being just a little bit different.”

Testing carried out around 200 days after the transplant showed that in both patients host cells had been almost entirely replaced by donor-derived PBMCs; only 0.00041-0.00081% of PBMCs were still host-derived in one patient, and the distribution was almost identical in the other patient.

Donor cells seem to be protected “by the fact that we kept them on antiretroviral therapy during and after transplantation while the residual reservoir was decaying and the new donor cells were taking over”, said Dr Henrich.

The researchers are careful not to describe their findings as a functional cure. Professor Dan Kuritzkes of

Brigham and Women’s Hospital and Harvard Medical School, also a member of the research group, commented that previous studies of structured treatment interruption showed that the majority of patients had experienced viral rebound within two to four weeks, virtually everyone was viremic by week eight, and most reached a plateau in viral rebound by weeks 12 to 16. “In each study one or two patients tend to lag behind the others, so that’s why we’re being careful,” he said.

Researchers do not rule out the re-emergence of virus replication after a year, which is why intensive sampling will continue for the foreseeable future.

81 Henrich dismissed any suggestion that a future approach to either a functional or sterilising cure might involve stem cell transplants.

“This is not a practical strategy that we can do for most people with HIV. Stem cell transplantation is dangerous. There can be up to 20% mortality associated with stem cell transfer in the first year after transplantation,” Dr Henrich told reporters.

The chief value of the study will be in what it tells researchers about the reductions in HIV DNA that might need to be achieved in order to control HIV off treatment, Timothy Henrich concluded.

“How low do we need to go – what level of reduction of the reservoir do you need in order to achieve a lasting impact? We hope our study will shed light on this important question.”

Reference

Henrich T et al. In depth investigation of peripheral and gut HIV-1 reservoirs, HIV-specific cellular immunity, and host microchimerism following allogeneic hematopoetic stem cell transplantation. 7th International AIDS Society

Conference on HIV Pathogenesis, Treatment and Prevention, Kuala Lumpur, abstract WeLBA05, 2013. View the abstract on the IAS conference website.

Source: http://www.aidsmap.com/Two-stem-cell-transplant-recipients-now-controlling-HIV-off- treatment/page/2692244/

IAS: Patients Remain HIV-Free After Stem Cell Transplant HIV-1 undetectable in blood, rectal tissue after allogeneic hematopoietic stem cell transplant

WEDNESDAY, July 3 (HealthDay News) -- For two HIV-1 infected patients who underwent reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC alloHSCT), HIV-1 remained undetectable in peripheral blood and rectal tissue up to 4.3 years after transplantation, according to a study presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, held from June 30 to July 3 in Kuala Lumpur, Malaysia.

Timothy J. Henrich, M.D., from Brigham and Women's Hospital in Boston, and colleagues examined the longitudinal effects of HSCT on host microchimerism and HIV-specific cellular immunity. Peripheral blood mononuclear cells (PBMCs), obtained by leukapheresis, were tested for residual HIV-1 DNA or replication- competent proviruses up to 4.3 years following RIC alloHSCT. Participants included two HIV patients who underwent RIC-alloHSCT, a third who died six months post-transplantation from recurrent lymphoma, and a fourth autologous HSCT patient who served as a control.

The researchers found that, in the two RIC-alloHSCT patients, no HIV-1 DNA was detected from PBMCs. In addition, no HIV-1 p24 antigen was detected by viral co-culture from purified CD4+ T cells, nor was any HIV-1 detected in rectal tissue. Post-HSCT, residual host cells constituted less than 0.001 percent of PBMCs. Before or

82 after allogeneic or autologous HSCT, no human leukocyte antigen-specific or pooled HIV-1 peptides elicited a strong HIV-specific immune response.

Source: http://www.physiciansbriefing.com/Article.asp?AID=677995

Part 2: December 2013 / January 2014

Wire

Relapse of "cured" HIV patients spurs AIDS science on

Thu Jan 2, 2014 5:15am EST

* AIDS researchers learn lessons from relapse of Boston men * Setback underlines need for sensitive tests for hidden HIV * Experts say two-pronged approach must be way forward

By Kate Kelland, Health and Science Correspondent

LONDON, Jan 2 (Reuters) - Scientists seeking a cure for AIDS say they have been inspired, not crushed, by a major setback in which two HIV positive patients believed to have been cured found the virus re-invading their bodies once more.

84 True, the news hit hard last month that the so-called "Boston patients" - two men who received bone marrow transplants that appeared to rid them completely of the AIDS-causing virus - had relapsed and gone back onto antiretroviral treatment.

But experts say the disappointment could lay the basis for important leaps forward in the search for a cure.

"It's a setback for the patients, of course, but an advance for the field because the field has now gained a lot more knowledge," said Steven Deeks, a professor and HIV expert at the University of California, San Francisco.

He and other experts say the primary practical message is that current tests designed to detect even very low levels of HIV present in the body are simply not sensitive enough.

As well as having the human immunodeficiency virus (HIV), the Boston patients both also had a type of blood cancer called lymphoma, for which they were treated using bone marrow transplants - one man in 2008 and the other in 2010.

They continued taking the antiretroviral AIDS drugs, but eight months after each patient's transplant, doctors found they could not detect any sign of HIV in their blood.

In the early part of 2013, both patients decided to stop taking their AIDS drugs and both appeared to remain HIV-free - prompting their doctors, Timothy Henrich and Daniel Kuritzkes from Boston's Brigham and Women's Hospital, to announce at a conference in July that they may have been cured.

Yet in December came news that one of the men had begun to show signs of an HIV rebound by August, while the second patient had a relapse in November.

Henrich said the virus' comeback underlined how ingenious HIV can be in finding hiding places in the body to evade attack efforts by the immune system and by drug treatment.

"Through this research we have discovered the HIV reservoir is deeper and more persistent than previously known and that our current standards of probing for HIV may not be sufficient," he said, adding that both patients were "currently in good health" and back on antiretroviral therapy.

INSPIRATION

Barely a decade ago, few HIV scientists would have dared put the words HIV and cure in the same sentence. Yet some intriguing and inspiring cases in recent years mean many now believe it is just a question of time before a cure is found.

First was the now famous case of Timothy Ray Brown, the so-called "Berlin patient," whose HIV was eradicated by a complex treatment for leukaemia in 2007 involving the destruction of his immune system and a stem cell transplant from a donor with a rare genetic mutation that resists HIV infection.

Such an elaborate, expensive and life-threatening procedure could never be used as a broad-spectrum approach for the world's 34 million HIV patients. But the results in Brown focussed scientific attention on a genetic mutation known as 'CCR5 delta 32' as a target for possible gene therapy treatment.

Then last March, French scientists who followed 14 HIV-positive people known as the "Visconti patients", who were treated very swiftly with HIV drugs but then stopped treatment, said that even after seven years off therapy, they were still showing no signs of the virus rebounding.

That announcement came only weeks after news of the "functional cure" of an HIV-positive baby in Mississippi who received antiretroviral treatment for 18 months from the day she was born. By the time she was two this appeared to have stopped the virus replicating and spreading.

A "functional cure" is when HIV is reduced to such low levels that it is kept at bay even without treatment, though the virus can still be detected in the body.

85 Sharon Lewin, an HIV expert at Monash University in Australia, said all these developments, as well as the setback suffered by the Boston patients, inspired scientists to investigate many different approaches in the search for a cure.

"We've learnt many things here - and one of the most important is that a tiny, tiny amount of virus can get the whole thing going again," she told Reuters. "It's a clear message that we need better ways to pick up the virus."

Scientists are now more convinced than ever that a two-pronged approach which aims to firmly suppress the virus while bolstering the immune system provides the best way forward.

"We need to attack in two ways - reduce the virus to very low levels and also to boost the immune response. We can't do one without the other," said Lewin.

"So we still have to think of other creative ways to control HIV. And it's still early days... before we can say which approach is likely to be the winner." (Reporting by Kate Kelland, editing by Gareth Jones)

Source: http://www.reuters.com/article/2014/01/02/health-aids-cure-idUSL6N0KB15A20140102

HIV Returns in Two Men Thought Cured After Stem Cell Transplant By Simeon Bennett Dec 7, 2013

Two HIV-infected men who were thought to be clear of the virus after having stem cell transplants have had the AIDS-causing pathogen return, their doctors said, scuppering hopes their cases might lead to a cure.

The two Boston men, who were also suffering from lymphoma, had no trace of the virus eight months after the transplants, researchers led by Timothy Henrich at Brigham and Women’s Hospital said in July, though they said it was too early to say the men had been cured. The virus reappeared in one of the men in August and in the other in November, Henrich said in a statement after presenting the results at an AIDS meeting in Florida yesterday.

The setback leaves just two people known to have been cured of HIV infection: Timothy Ray Brown, a San Francisco man who has been clear of the virus since having a bone marrow transplant for leukemia in 2007, and an infant born with HIV in Mississippi in 2010 who was considered cured after intensive treatment shortly after birth.

The new findings are “disappointing, but scientifically significant,” Henrich said in a statement. “We have discovered the HIV reservoir is deeper and more persistent than previously known and that our current standards of probing for HIV may not be sufficient to inform us if long-term HIV remission is possible if antiretroviral therapy is stopped.”

86 While AIDS drugs such as Gilead Sciences Inc. (GILD)’s Atripla reduce HIV to undetectable levels in the body, making it a chronic disease, they don’t completely clear it. The virus hides in so-called reservoirs, where it switches off the normal process of replication, enabling it to avoid detection by the medicines. Reactivating Virus

Studies have shown that when patients who have the virus under control stop treatment, the latent HIV reactivates and comes roaring back, forcing victims to resume daily pill therapy.

The two Boston men had stopped treatment following their transplants without the virus rebounding immediately, suggesting they may have been cured. In one man, the virus reappeared 12 weeks after he stopped treatment, and after 32 weeks in the other man. Both have resumed therapy and are in good health, Henrich said.

Source: http://www.bloomberg.com/news/2013-12-07/hiv-returns-in-two-men-thought-cured-after-stem-cell- transplant.html

HIV returns in Boston patients thought to be cured The two patients have shown a resurgence of the virus after it was announced earlier this year that they were HIV-free. Researchers said the return of the virus could be attributed to HIV reservoirs that are difficult to find in the body. Posted By Ananth Baliga | Dec. 6, 2013

87 Two Boston-based HIV patients, previously believed to be cured of HIV are now showing traces of the virus in their blood. Pictured above are HIV cells, in green, budding from a lymphocyte. (Credit: CDC/C. Goldsmith)

Dec. 6 (UPI) -- Two HIV patients from Boston, earlier believed to be cured of HIV, are now showing traces of the virus in their blood, researchers said.

Boston researchers earlier in the year reported that two patients who had undergone bone marrow transplants for cancer were HIV-free, after they were asked to stop their antiretroviral medication.

The excitement was short-lived as researchers announced Thursday that the virus had returned in both patients, suggesting that the virus can hide in the body without being detected.

Timothy Henrich of Brigham and Women’s Hospital released the initial findings at an international conference of AIDS researchers in Florida, to help inform other studies based on earlier claims.

“We felt it would be scientifically unfair to not let people know how things are going, especially for potential patients,” said Henrich.

The two patients had been battling HIV for years before their marrow transplants for cancer. After surgery, they agreed to stop the antiretroviral medication to test whether that medication was keeping the HIV in check or if it was the transplant fighting the virus in their bodies.

After weeks of testing their blood, researchers in July reported that they could not find any traces of the virus.

But in August the virus returned in one of the patients, who then resumed taking HIV medication. As an ethical gesture the second patient was offered medication as well. The patient declined.

But last month after being HIV-free for eight months, the virus returned to the second patient, who went back on medication.

According to Heinrich, the return of the virus can be attributed to HIV reservoirs, latent cells carrying the genetic code of HIV.

“This suggests that we need to look deeper, or we need to be looking in other tissues . . . the liver, gut, and brain,” Henrich said. “These are all potential sources, but it’s very difficult to obtain tissue from these places so we don’t do that routinely.”

At present the only patient believed to have been cured of HIV is Timothy Ray Brown. German doctors claimed in 2009 that Brown had been cured off HIV after receiving bone marrow transplant for leukemia.

While doctors are disappointed with the new findings they said it would help advance better strategies to battle the virus.

“There are a lot of hurdles,” said Dr. Steven Deeks, professor of medicine at the University of California, San Francisco. “But this [the Boston researchers’ approach] dramatically advanced the cure research agenda.”

Source: http://www.upi.com/blog/2013/12/06/HIV-returns-in-Boston-patients-thought-to-be- cured/8131386361344/#ixzz2rnzKlKPA

Tras dejar de tomar los antivirales Los pacientes con VIH 'curados' tras un trasplante de médula recaen en la enfermedad

Foto: GETTY

LONDRES, 2 Ene. (Reuters/EP) -

El pasado mes de julio investigadores de la Facultad de Medicina de Harvard y el Hospital Brigham and Women de Boston (EEUU) anunciaban que una terapia con células madre podría haber eliminado el VIH en dos personas infectadas por el virus, tras no detectar signos de la infección en estos pacientes trasplantados de médula ósea hacía años. Sin embargo, tras dejar de tomar los antirretrovirales se ha vuelto a detectar la enfermedad en los dos pacientes 'curados' del virus que causa el sida.

Los investigadores, que afirmaron que este resultado les incentiva más que desalienta, informaron el pasado mes de diciembre que los llamados 'pacientes de Boston' habían sufrido sendas recaídas y tenido que regresar al tratamiento antirretroviral.

Los expertos destacan que este resultados podría ser la base para conseguir importantes avances en la búsqueda de una cura a esta enfermedad. "Es un revés para los pacientes, por supuesto, pero un avance para el campo (científico) porque ahora ha ganado mucho más conocimiento", ha señalado Steven Deeks, especialista en VIH de la University of California, en San Francisco.

Deeks y otros expertos señalan que el principal mensaje práctico de estas recaídas es que las pruebas actuales diseñadas para detectar incluso pequeños niveles de VIH presentes en el cuerpo simplemente no son lo suficientemente sensibles.

Además de tener el virus de la inmunodeficiencia humana (VIH), los pacientes de Boston tenían un tipo de cáncer sanguíneo denominado linfoma, por el cual habían sido tratados con trasplantes medulares, uno en 2008 y

89 el otro en 2010. Ambos pacientes siguieron tomando fármacos antirretrovirales contra el sida, pero ocho meses después de los trasplantes, los médicos no lograron detectar ninguna señal de VIH en su sangre.

A comienzos del pasado año, ambos pacientes decidieron dejar de tomar la medicación y, pese a no seguir el tratamiento, los analisis mostraban que seguían libres de VIH, lo que llevó a sus médicos -Timothy Henrich y Daniel Kuritzkes- a anunciar en una conferencia que los pacientes se habían curado.

Sin embargo, en diciembre se dio a conocer la noticia de que uno de los dos hombres había empezado en agosto a mostrar signos de recurrencia Actualmente, ambos pacientes tienen "en buen estado de salud" y han retomado la terapia antirretroviral. Según Henrich, "el regreso del virus demuestra cuán ingenioso puede ser el VIH para hallar zonas del organismo donde esconderse y evadir los esfuerzos por atacarlo del sistema inmune y de los tratamientos farmacológicos".

"A través de esta investigación hemos descubierto que el reservorio del VIH es más profundo y más duradero de lo que creíamos anteriormente y que nuestros estándares actuales de evaluación del VIH no serían suficiente", ha señalado.

Source: http://www.infosalus.com/salud-bienestar/noticia-pacientes-vih-curados-trasplante-medula-recaen- enfermedad-20140102173218.html

Aids: ritorno Hiv in pazienti Boston ispirazione per nuove terapie 13:54 02 GEN 2014

(AGI) - Washington, 2 gen. - Il ritorno dell'Hiv nei due "pazienti Boston", che si pensava fossero stati curati dopo il trapianto di midollo osseo, non ha "schiacciato" le speranze dei medici. Anzi, a detta dei ricercatori, la recrudescenza della malattia potrebbe servire da ispirazione per ulteriori passi avanti. ''Chiaramente non e' stata una notizia positiva per i pazienti - ha spiegato Steven Deeks, esperto di Hiv della University of California di San Francisco - ma abbiamo guadagnato molta conoscenza su come funziona il virus''. Uno dei primi aspetti positivi della vicenda, a detta di Deeks e colleghi, e' stato il fatto di aver scoperto che i test attuali sviluppati per rilevare anche tracce minime di Hiv non sono abbastanza sensibili. I pazienti Boston avevano entrambi, oltre all'Hiv, un linfoma che era stato trattato con trapianto di midollo osseo (nel 2008 per uno e nel 2010 per l'altro).

Otto mesi dopo il trapianto, continuando a prendere farmaci antiretrovirali, i medici non riuscirono piu' a rintracciare l'Hiv nel loro sangue. All'inizio del 2013, i pazienti decisero con i dottori di non assumere piu' farmaci anti-retrovirali e a luglio, permanendo l'assenza del virus, gli scienziati del Brigham and Women's Hospital annunciarono che erano stati curati. Purtroppo, il virus torno' ad agosto per il primo e a novembre per il secondo. Attraverso questi casi, gli scienziati hanno detto di aver imparato che il virus ha riserve piu' profonde e persistenti di quanto si supponeva. (AGI) .

Source: http://www.agi.it/research-e-sviluppo/notizie/201401021354-eco-rt10092- aids_ritorno_hiv_in_pazienti_boston_ispirazione_per_nuove_terapie

Broadcasting

Hoped-For AIDS Cures Fail In 2 Boston Patients by RICHARD KNOX December 06, 201312:20 PM i BSIP/UIG via Getty Images HIV has reappeared in the blood of two Boston patients who scientists had hoped had been cured of their infections.

This disappointing development, reported by The Boston Globe's Kay Lazar, is yet another cautionary tale of how researchers can never afford to underestimate the human immunodeficiency virus's ability to hide out in patients' bodies and overcome their most ingenious efforts to eliminate it. The Boston patients have stirred considerable hope among HIV researchers since mid-2012, when scientists cautiously raised the possibility that bone marrow transplants had eliminated the virus from their systems. The only person known to be cured of HIV so far is 47-year-old American Timothy Brown, widely known as the Berlin patient because he received a bone marrow transplant in Germany six years ago. AMississippi toddler treated with antiviral drugs within 36 hours of birth might be deemed the second cure if she remains free of HIV. But the Boston patients, who have not been named, would have represented something new and encouraging.

91 The Berlin patient received bone marrow from a donor who was genetically resistant to HIV infection. But the Boston patients' marrow donors had no such rare advantage, raising the hope that anti-HIV drugs might be enough to eliminate the virus — at least when combined with a bone marrow transplant.

Scientists also thought an immune reaction called graft-versus-host disease, or GVH, might have contributed to the apparent disappearance of HIV in the Boston patients' systems. In GVH, the transplanted marrow cells attack and kill the patient's native bone marrow — possibly helping to get rid of any cells where HIV might lurk.

In July, Dr. Timothy Henrich of Brigham and Women's Hospital in Boston told an international meeting of AIDS researchers that two AIDS patients might have been cured by stem cell transplants. Lai Seng Sin/AP

But alas, those hopes were recently dashed. Researchers announced the possible Boston cures at an AIDS meeting in Kuala Lumpur in July, when their patients had been off anti-HIV drugs for seven and 15 weeks. (Their bone marrow transplants were three and five years earlier, for Hodgkin's disease, but they had kept taking the antiretroviral drugs until earlier this year.)

But in August, the virus reappeared in one man's blood. And in November, HIV re-emerged in the second patient. Both patients have gone back on antiretroviral medications, presumably for the rest of their lives. The drugs have proven effective in suppressing the virus in patients' systems, but not in eliminating it.

The Boston researchers decided to disclose the news at an AIDS meeting in Florida, because scientists in other institutions had already begun planning experiments to replicate the hoped-for cures in other bone marrow transplant patients infected with HIV.

Disappointing as the Boston experiment is, researchers say it has advanced the cause of HIV cure research. Just last Monday, President Obama announced a $100 million project to push that cause forward — a reflection of optimism among AIDS specialists after years of rarely uttering what one prominent researcher calls "the c-word."

Researchers say even negative results such as those from the Boston experiment contain important clues about what will be required to cure HIV infections.

"This is certainly telling us a lot about persistence, what we need to do, and how low we need to drop the levels of HIV reservoirs in order to allow patients to achieve remission," Dr. Katherine Luzuriaga of the University of Massachusetts told The Globe. Luzuriaga has a special reason to pay close attention. She's a member of the team following the Mississippi child to see if that cure is for real.

Source: http://www.npr.org/blogs/health/2013/12/06/249242591/hoped-for-aids-cures-fail-in-2- boston-patients

AIDS virus comes back in men who hoped for cure Maggie Fox NBC News Dec. 9, 2013

Two men who had hoped they might be cured of an HIV infection after getting bone marrow transplants for cancer got some bad news, doctors said Monday. The virus has come back.

The intense and life-threatening treatments for cancer appeared to have wiped the virus out, and the two men took a chance and, earlier this year, stopped taking the HIV drugs that were keeping the virus under control.

At first, no signs of the virus could be found. But their doctors, cautious after decades of fighting a tricky virus, didn’t declare a cure.

“It’s disappointing,’ said Dr. Daniel Kuritzkes of Brigham and Women’s Hospital in Boston, who worked with Dr. Timothy Henrich to treat and study the two men.

“But it’s still taught us a great deal.”

The case of the two men shows that even if you make HIV seemingly disappear, it can be hiding out in the body and can re-activate. It might be somewhere other than in blood cells, Henrich said. Other scientists suspect HIV might be able to hole up in organs or inside the intestines.

“Through this research we have discovered the HIV reservoir is deeper and more persistent than previously known and that our current standards of probing for HIV may not be sufficient to inform us if long-term HIV remission is possible if antiretroviral therapy is stopped,” Henrich said.

“Both patients have resumed therapy and are currently doing well.” Neither man wants to be named.

Henrich, Kuritzkes and colleagues had actively looked for HIV patients with leukemia or lymphoma who had received bone marrow stem cell transplants.

93 In a bone marrow transplant, the patients' own bone marrow is destroyed, usually with chemotherapy or radiation, and replaced with a tissue-matched transplant from a donor.

Kuritzkes, Henrich and colleagues wanted to replicate the case of Timothy Brown, also known as the "Berlin patient," who was treated for leukemia with a bone marrow transplant that happened to come from a donor with a genetic mutation that makes immune cells resist HIV infection. The transplant replaced his own infected cells with healthy, AIDS-resistant cells, and he remains free of the virus more than five years later.

Then there is the widely reported case of a baby in Mississippi whose HIV infection disappeared after unusually early and aggressive drug treatment.

The human immunodeficiency virus that causes AIDS is transmitted sexually, in blood, on infected needles, at birth and in breast milk.

Doctors had hoped that if patients got bone marrow transplants while taking HIV drugs, the virus would not be able to take hold in the freshly transplanted bone marrow cells - which are the source of new blood cells.

It's not a lost cause, Kuritzkes said.

“We are continuing to recruit patients into the study,” Kuritzkes said. He said several patients who have been treated for cancer are being studied. It might be that people who weren’t infected with HIV as long before they got treated might be easier to “cure.”

“It’s not a reason to give up research on a cure,” he said.

Source: http://www.nbcnews.com/health/aids-virus-comes-back-men-who-hoped-cure-2D11709509

HIV returns in "cured" Boston patients

By MICHELLE CASTILLO CBS NEWS December 6, 2013, 12: 42 PM

Researchers announced today that two men they previously believed to be “cured” of HIV are now showing traces of the virus in their blood.

Dr. Timothy Henrich, associate professor of infectious diseases at Brigham and Women’s Hospital in Boston, announced the resurgence of the virus at an international conference on AIDS research in Florida Thursday, the Boston Globereported. He said the fact that these two men were showing signs of HIV means that the virus can lurk in places in the body where it is hard to find.

The two HIV-positive men previously made headlines in July, when Henrich announced that they were no longer showing any detectable traces of HIV in their body. The patients had received stem cell transplants after they had been diagnosed with Hodgkin’s lymphoma, a type of blood cancer, and doctors believed this transplant had allowed their body to get rid of the virus. They had stopped taking antiretroviral medications for 15 weeks and seven weeks respectively at the time of the announcement.

Man "cured" of AIDS: Timothy Ray Brown

The second patient decided to stay off the medication, but eight months after he had been “cured” the doctors found traces of HIV. He was placed on antiretrovirals again.

According to government estimates, about 1,148,200 persons 13 and older were infected with HIV in the U.S. in 2009. Around 18.1 percent of those people had not been diagnosed yet.

Another man, Timothy Ray Brown, similarly announced that he had been “cured” of HIV when he received a stem cell transplant. Brown, who had leukemia, received a donation from a person with a genetic mutation called CCR5-delta32, which made them HIV-resistant. Researchers said in July 2012 that they found traces of HIV in Brown’s blood, but the patient claims those viruses are dead and cannot replicate. The Boston men's stem cell donors did not have the CCR5-delta32mutation.

WATCH VIDEO: http://www.cbsnews.com/videos/hiv-infected-infant-cured

HIV-infected infant cured A Mississippi baby born HIV-positive was also determined to be "cured" of the virus. Instead of receiving a stem cell transplant, she was given powerful three- drug infusion within 30 hours after birth. The mother had not been diagnosed with HIV until she was in labor, and did not receive any prenatal treatments to prevent the spread of the virus to her baby.

96 Researchers said in Oct. the baby still appears to be HIV-free.

Henrich said that despite the failure to eradicate HIV from the two men, researchers learned a lot that would allow them to make improvements for future treatments.

“We go back to the drawing board,” Henrich said. “It’s exciting science, even if it’s not the outcome we would have liked.”

Source: http://www.cbsnews.com/news/hiv-returns-in-cured-boston-patients

HIV returns in two patients after bone marrow transplant By Ray Sanchez, Sho Wills and Saundra Young, CNN December 9, 2013 -- Updated 1031 GMT (1831 HKT)

Watch video: http://edition.cnn.com/2013/12/07/health/hiv- patients/index.html?iref=storysearch#

HIV returns in transplant patients STORY HIGHLIGHTS

 HIV returns in two patients who doctors hoped had been cured of the virus  The virus became undetectable in both patients about eight months after bone marrow transplants

97  A researcher says the return of the virus is "disappointing, but scientifically significant"

(CNN) -- HIV has returned in two patients who doctors hoped had been cured of the virus following bone marrow transplants, the Boston researcher who treated them said Saturday.

The HIV virus became undetectable in both patients approximately eight months after the transplant. The men remained on antiretroviral therapy until the spring of 2013.

"The return of detectable levels of HIV in our patients is disappointing, but scientifically significant," Dr. Timothy Henrich, a researcher at Brigham and Women's Hospital in Boston, said in a statement. "We have demonstrated HIV can be reduced to undetectable levels by very sensitive research assays and the virus persists."

The virus became detectable in one patient in August -- 12 weeks after ceasing antiretroviral therapy. In the other man, HIV became detectable this month, 32 weeks after antiretroviral therapy ceased.

"Through this research we have discovered the HIV reservoir is deeper and more persistent than previously known and that our current standards of probing for HIV may not be sufficient to inform us if long-term HIV remission is possible if antiretroviral therapy is stopped," Henrich said. "We have also learned that there may be an important long-lived HIV reservoir outside the blood compartment."

Dr. Daniel K. Kuritzkes, another researcher at Brigham and Women's Hospital, said the cases demonstrate that the virus may persist even when there is no evidence in the blood.

"We need to develop better and more sensitive tools to detect the virus as we continue to pursue novel strategies for HIV eradication," he said. "Our results also show that the immune system can play a major role in reducing the viral reservoir, but may not be able to do the job alone. It is likely that a combination of drugs and immune therapies that target the reservoir will be needed to establish long-term remission of HIV infection."

In July, when the cases were first reported at the International AIDS Society Conference in Kuala Lumpur, Malaysia, experts stopped short of calling the two cured and said the treatment is not a viable option for the majority of HIV patients.

After the patients ceased antiretroviral therapy, they were tested for HIV every seven to 10 days. Both resumed antiretroviral therapy after the virus was detected. They are in good health and the virus is suppressing as expected.

Brigham and Women's Hospital researchers will continue to monitor the patients and measure their HIV levels as part of a new study of the very early initiation of antiretroviral therapy after HIV rebound.

The men, whose identities were withheld, had been on antiretroviral drug therapy for years before being diagnosed with lymphoma, a cancer of the lymph nodes.

Both underwent intensive chemotherapy followed by bone marrow transplants to treat the cancer. They remained on antiretroviral therapy.

Approximately four months after the transplant doctors were still able to detect HIV in their blood, but six to nine months later, all traces of the virus were gone.

Some patients make it up to eight weeks before the virus returns, but the virus returns eight to 10 weeks after therapy is stopped in the vast majority of patients, Henrich said in July. Not so for these two men, however.

HIV discovery 'will change your life forever'

The two men were compared with Timothy Ray Brown, also known as the "Berlin Patient." Brown is thought to be the first person ever "cured" of HIV/AIDS.

98 In 2007, Brown had a stem cell transplant to treat his leukemia. His doctor searched for a donor with a rare genetic mutation called CCR5 delta32 that makes stem cells naturally resistant to HIV infection.

Today, the virus is still undetectable in Brown's blood, and he is still considered to be "functionally cured." A functional cure means the virus is controlled and will not be transmitted to others.

The stem cell transplant procedure, however, is very dangerous because a patient's immune system has to be wiped out in order to accept the transplant.

Using a stem cell transplant to treat HIV is not for most patients, and only 1% of Caucasians -- mostly Northern Europeans -- and no African-Americans or Asians have the CCR5 delta32 mutation, researchers say.

The transplant is still not a practical strategy for the majority of HIV patients, and the risk of mortality is up to 20%, Henrich says.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, agreed.

"This is not a practical approach for someone who does not need a stem cell transplant since the transplant and its preparation and its subsequent need for chronic immunosuppression is a risky procedure," Fauci said.

HIV 'cure' in toddler offers 'global hope'

Even though the two patients showed a reduction of the virus in the blood, it could still be in some tissue -- the brain or gastrointestinal tract, for instance, Henrich said.

Two years later, there is no sign of HIV in the child's blood, making her the first child to be "functionally cured" of HIV.

The Foundation for AIDS Research, or amfAR, helped fund the study.

"These findings clearly provide important new information that might well alter the current thinking about HIV and gene therapy," said amfAR CEO Kevin Robert Frost.

"Dr. Henrich is charting new territory in HIV eradication research," said Dr. Rowena Johnston, amfAR vice president and director of research.

Source: http://edition.cnn.com/2013/12/07/health/hiv-patients/index.html?iref=storysearch

Newspapers, magazines and blogs

Marrow Transplants Fail to Cure Two H.I.V. Patients

By DONALD G. McNEIL Jr. Published: December 6, 2013

Two patients in Boston whom doctors hoped they had cured of bothH.I.V. and cancer through bone-marrow transplants have seen their H.I.V. return, researchers said Friday.

Although there was never an expectation that risky bone-marrow transplants would soon be a routine treatment for H.I.V., the news was frustrating to AIDS experts. Many had hoped that the “graft versus host” battle that virtually all such transplants set off could become a potent weapon, at least in a few high-risk cases.

In July, when the two cases were first discussed at an international AIDS conference, it was suggested that they might echo the case of Timothy Ray Brown, the famous “Berlin patient,” who has been free of H.I.V. since a 2008 bone-marrow transplant from a donor with a rare mutation that confers resistance to the virus. Some experts regard him as the first patient cured of H.I.V.

The resurgence of the virus in the two patients is “disappointing but scientifically significant,” Dr. Timothy J. Henrich, who oversees their care at Brigham and Women’s Hospital in Boston, said in a statement.

Both men are back on antiretroviral drugs and “in good health,” Dr. Henrich added.

100 Dr. Steven G. Deeks, an AIDS researcher at the University of California, San Francisco, called the results “disappointing but not unexpected.” The cases demonstrate that the virus can hide so deeply in the body that it cannot be detected by the most sophisticated lab work.

“It just takes one virus in one cell,” he said.

Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, said the failure “doesn’t put an end to this avenue of research, but it certainly does put a damper on it.”

The two Boston men already had H.I.V. when they developed lymphoma, a blood cancer. Both kept taking antiretroviral drugs for H.I.V. while their bone marrow was weakened to prepare for the transplants. They stayed on the drugs for years afterward.

Mr. Brown, in Berlin, received marrow from a donor with a rare mutation, known as delta 32, that makes blood cells virtually impervious to H.I.V. The Boston men’s donors did not have the mutation; they were simply good matches.

Dr. Henrich hoped that the new blood cells from the new marrow would find and kill all the old ones, which were both cancerous and infected with H.I.V., and that the antiretroviral drugs would protect the new blood cells against H.I.V.

When no virus could be found in the men for months, they stopped taking the drugs.

In July, Dr. Henrich announced that one man had been off the drugs for seven weeks and the other for 15, and that no virus had been found. (It normally returns within a month or so.)

At that time, he and other researchers referred to the men as being in remission, not cured. But Dr. Henrich warned that the virus “could come back in a week, or in six months.”

On Friday, he said it had returned in one man in August and in the other man last month.

Apparently, Dr. Fauci said, either some old infected cells survived or they infected some new ones before succumbing.

While there may still be a way to make bone-marrow transplants work with H.I.V. patients, Dr. Fauci said, “it tells you for sure that it’s not going to be easy.”

A version of this article appears in print on December 7, 2013, on page A13 of the New York edition with the headline: Marrow Transplants Fail To Cure Two H.I.V. Patients

101

Source: http://www.nytimes.com/2013/12/07/health/marrow-transplants-fail-to-cure-two-hiv- patients.html?partner=rssnyt&emc=rss&_r=1&

HIV virus returns after cure hope rose 2 Boston patients had transplants of marrow, halted powerful drugs By Kay Lazar | Globe Staff

December 06, 2013

Steve Forrest/International AIDS/file

The rebound of the virus shows its persistence, and that it can hide in places in the body where it’s hard to find, said the lead scientist, Dr. Timothy Henrich of Brigham and Women’s Hospital.

Boston researchers are reporting the return of the HIV virus in two patients who had become virus-free after undergoing bone marrow transplants, dashing hopes of a possible cure that had generated widespread excitement.

The rebound of the virus shows its persistence, and that it can hide in places in the body where it’s hard to find, said the lead scientist, Dr. Timothy Henrich of Brigham and Women’s Hospital. But he said the team has gleaned significant clues from the cases for designing next-generation treatments to battle the virus, which causes AIDS.

Henrich, who presented the preliminary findings Thursday at an international conference of AIDS researchers in Florida, said doctors pinpointed signs of the virus in both patients, who had beaten back the infections to undetectable levels earlier this year. The patients underwent bone marrow transplants several years ago for cancer, and had since stopped their powerful antiretroviral medications, which are typically given to those infected with the virus to keep it in check.

Other researchers who heard the presentation said the results were disappointing but the Boston team’s approach and data will dramatically advance strategies for battling HIV.

Henrich, a Brigham infectious diseases associate physician, said in an interview that the researchers decided to release their initial findings, before analyzing all the results, so others in the field could know as soon as

102 possible. Other scientists were designing similar studies, with HIV patients who had bone marrow transplants, based on the earlier Boston findings.

“We felt it would be scientifically unfair to not let people know how things are going, especially for potential patients,” Henrich said.

The two patients in the Boston study had battled HIV for years. They agreed to stop taking their HIV medications earlier this year to test whether the medicine was holding the infections in check, or whether it was the transplant of healthy donor bone marrow cells each received that was vanquishing signs of the virus in their bodies. Both had received the transplants after chemotherapy and other treatments had failed to stop their Hodgkin’s lymphoma, a cancer of the blood.

For weeks, Henrich’s team carefully tested the patients’ blood, searching for signs of HIV. In July, with one patient off the HIV medications for seven weeks, and the other patient off for 15, the scientists reported their early, encouraging results: They could find no trace of the virus in their blood cells.

But in August, the scientists detected HIV in one of the patients, who then resumed taking medication. The other remained seemingly HIV-free. Concerned about the ethics of continuing the study, the scientists gave the patient the choice of going back on the drugs. The patient opted to stay off the medicine.

Last month, after eight months with no HIV detected, signs of the virus reemerged and the patient went back on medication, too.

Henrich said the reemergence of the virus demonstrates that HIV reservoirs — latent cells that carry the genetic code of HIV — are lurking deeper in the body and are more persistent than scientists had realized.

To date, there is only one patient believed to have been cured of HIV. German doctors in 2009 reported that an American, Timothy Ray Brown, was given a bone marrow transplant for leukemia and appeared to have been cured of HIV as well.

Brown, known as the “Berlin patient,” received bone marrow from a donor who carried a rare gene mutation, CCR5-delta32, which is thought to provide resistance to HIV. Previously, researchers had not observed similar results with ordinary donor marrow, such as those cells given to the Boston patients.

In preparation for his transplant, Brown also received massive doses of harsh chemotherapy and radiation treatments to knock out the HIV infection, an extreme approach not practical for widespread use, said Dr. Steven Deeks, an HIV researcher and professor of medicine at the University of California, San Francisco. The Boston patients received much lower doses before their transplants.

“There are a lot of hurdles,” said Deeks, who was at the Florida meeting. “But this [the Boston researchers’ approach] dramatically advanced the cure research agenda.”

Henrich and other researchers say bone marrow transplants, which are risky and can be lethal, are not a practical or ethical approach to treating HIV, especially in patients who do not have cancer.

But the Boston findings help researchers better understand how and where HIV persists in the body, potentially helping them design treatments that may be more precise in eradicating the virus.

“This is certainly telling us a lot about persistence, what we need to do, and how low we need to drop the levels of HIV reservoirs in order to allow patients to achieve remission,” Dr. Katherine Luzuriaga, professor of molecular medicine, pediatrics and medicine at UMass Medical School, said by phone from the conference.

103 Luzuriaga and colleagues recently reported that a 3-year old, who was born with HIV and given antiretroviral drugs within 30 hours of birth, remains in remission despite being off medications for 18 months.

Henrich’s team is now scouring its data to figure out why one patient was able to fend off the virus’s return months longer than the other patient they studied. Among the factors they are scrutinizing are the age when each was infected with HIV, the manner of infection, and the levels of virus in each patient before they underwent bone marrow transplantation.

The team also plans to widen its study, enroll more HIV-infected patients who have had bone marrow transplants, and search for signs of infections in additional tissue before stopping HIV medications. Among the questions the researchers hope to answer is whether the timing of when HIV medication is halted may play a role in its reemergence.

“We go back to the drawing board,” Henrich said. “It’s exciting science, even if it’s not the outcome we would have liked.”

Source: http://www.bostonglobe.com/lifestyle/health-wellness/2013/12/05/hiv-virus-returns-after-cure-hope- rose/A2XYqmmYuh8MMVKAurDFxN/story.html

104

Dos de las tres personas que se creían ‘curadas’ del VIH han recaído

Los hombres habían abandonado los antivirales tras un tratamiento contra la leucemia

Emilio de Benito Madrid 2 ENE 2014

2013 se ha despedido en el mundo del VIH con una mala noticia: de los tres hombres que hace seis meses se creía que habían conseguido erradicar el virus de su cuerpo, en dos el patógeno ha reaparecido, según han comunicado sus médicos.

Los tres casos tenían una base común: se trataba de hombres que, además de la infección por VIH, habían sido tratados para curar una leucemia. Ello implica bombardear su médula ósea hasta casi destruirla, y regenerarla después con un trasplante de células madre de médula. El primero en seguir este riguroso tratamiento fue Timothy Brown, el paciente de Berlín, en 2008. En su caso se utilizó para el trasplante un tipo de médula cuyas células son resistentes al VIH. Brown ha sido la primera persona que ha conseguido dejar la medicación sin que el virus desaparezca.

En julio del año pasado se notificó que había otros dos casos parecidos, los conocidos como los pacientes de Boston. A mediados de año uno llevaba siete semanas y el otro el doble de tiempo sin tomar medicación y, para sorpresa de los médicos, el virus no había reaparecido. Son estos dos casos los que ahora se ha sabido que han vuelto a registrar niveles apreciables de VIH.

Lo normal, como dijo al presentar los resultados Timothy Henrich, uno de los médicos que les traba, es que una persona infectada que deje de tomar los antivirales registre un repunte en menos de un mes. Ello se debe a que la medicación, pese a todas sus mejoras, es capaz de eliminar el patógeno de la sangre y otros fluidos, pero no lo erradica. El VIH queda latente en lo que se denominan reservorios, unos refugios biológicos que están ubicados, sobre todo, en la médula y el sistema linfático. Al retirar la presión de los fármacos, el virus reaparece.

En este caso el proceso ha tardado mucho más, lo que indica que el tratamiento para la leucemia, que es muy agresivo, consiguió controlar la replicación del virus en gran medida, pero no de una manera completa. Y, como ha dicho Henrich, “basta con que quede un ejemplar del virus” para que vuelva a proliferar.

En cualquier caso, el resultado, que no es bueno, no ha sido visto como un gran fracaso por los autores. La posibilidad de tratar a los casi 35 millones de personas que hay en el mundo con VIH con un método tan agresivo y peligroso es inviable, así que estos casos se tomaban como un ejemplo de que había la posibilidad de erradicar el virus, aunque para ello había que desarrollar otro sistema. Mientras este llega, queda la opción de mantener el microorganismo a niveles indetectables, lo que basta para garantizar la calidad de vida de la inmensa mayoría de los afectados, y esto se puede conseguir con los fármacos actuales.

Source: http://sociedad.elpais.com/sociedad/2014/01/02/actualidad/1388676901_234237.html

105

El VIH muestra su fortaleza

 La quimioterapia más agresiva no lo erradica

 El virus rebrota en dos de los tres hombres se creían ‘curados’

Emilio de Benito Madrid 6 ENE 2014

Virus de la inmunodeficiencia infectando una célula.

Las esperanzas de que algún día las personas con VIH consigan erradicarlo han sufrido un traspiés. Los médicos que atendían a los dos pacientes de Boston, los hombres que tras someterse a un tratamiento para la leucemia parecía que habían erradicado el virus, dieron a finales de diciembre en un congreso en Miami la noticia de que habían recaído. Aún queda uno: Thimoty Brown, el paciente de Berlín, que lleva desde 2007 sin necesitar medicación y sin dar manifestaciones de que el virus se haya reactivado.

“Fue una bomba”, dice el infectólogo Santiago Moreno, del hospital Ramón y Cajal de Madrid, quien asistió a aquel congreso en Mami. “Uno llevaba 18 semanas y otro alrededor de medio año”, recuerda Moreno de los dos casos, que se habían presentado a mitad de julio en Kuala Lumpur (Malasia). En la mayoría de los casos, el virus reaparece alrededor de un mes después de suspenderse la medicación, por lo que había esperanzas de que los hombres hubieran superado ya esa fase de peligro, pero no ha sido así. “Nuestro gozo en un pozo. Con eso no es suficiente”, reflexiona Moreno, quien da además otros detalles: “En estas personas, el virus reapareció con inusitada violencia. Llegaron a niveles de carga viral [la concentración de VIH en sangre] muy superior al que habían tenido antes. Eso sí, en cuanto volvieron a tomar la medicación respondieron de inmediato”.

Al igual que en el caso de Berlín, los dos hombres tenían una leucemia. Fue precisamente al tratarles con una quimioterapia intensiva para destruir las células cancerosas cuando se creyó que se habían eliminado los reservorios del virus. “La principal diferencia es que, después de ello, al paciente de Berlín se le trasplantaron células madre de una variante resistente al VIH, y a los otros no”, explica Juan Berenguer, del Hospital Gregorio Marañón de Madrid y presidente del Grupo de estudio del Sida (Gesida) de la Sociedad Española de Enfermedades infecciosas y Microbiología Clínica (Seimc). Esa diferencia es la que hizo que en el caso de Brown no haya habido una recidiva del virus, y sí se haya producido en los otros dos.

106 Pero, más allá de los casos, lo que interesa a los expertos son las consecuencias, lo que se aprende de este fracaso. A corto plazo poco cambia para los afectados: “Nunca habíamos planteado tratar así a las personas con VIH”, dice Berenguer. “Los tratamientos actuales son muy eficaces y mucho menos peligrosos que una quimioterapia tan fuerte, que puede ser hasta mortal”, recalca. “Quitando cuestiones como la económica, y la muy importante del estigma, hoy día el sida es una enfermedad más de las que necesitan una medicación de por vida. ¡Qué más quisiera una diabético de 30 años que tener un tratamiento tan cómodo!”, afirma Berenguer.

Pero en lo que los especialistas están de acuerdo es en que estos tres casos (al que podría unirse el de una niña que también se supone curada del VIH después de ser sometida a una fuerte medicación con antivirales nada más nacer) era una prueba de concepto, una demostración de que algo que hasta poco se creía impensable: que una persona no solo controle el virus, sino que este desaparezca o quede en niveles tan bajos que el propio organismo, sin necesidad de pastillas, lo controle. Esto último es lo que se denomina una curación funcional, y expertos en el VIH como Robert Gallo, creen que ahora es algo posible. “He tenido dudas al respecto durante los últimos 30 años. Peor en el último me dije: ‘Hay que ser realista’. La curación funcional es un objetivo a nuestro alcance”, ha dicho Gallo.

Se trata de un proceso muy complicado porque el virus de la inmunodeficiencia es un retrovirus. Esto quiere decir que tiene una especial capacidad para esconderse, para refugiarse. No es solo que se meta en células del huésped (los glóbulos blancos para destruirlos, la médula o el sistema linfático para esconderse). Es que llega casi a desaparecer. Sus proteínas de cubierta se destruyen, y su material genético se integra en el de las células invadidas, camuflándose entre el resto de los genes del individuo. Desde ahí se manifiesta generando nuevos virus. Por eso es tan difícil de eliminar.

Ahora sabemos que la erradicación es posible", dice Santiago Moreno

Berenguer abunda en esta idea. “Para demostrar que un perro puedo hablar no haría falta hacer un ensayo doble ciego; bastaría con que hubiera uno que lo hace. El caso de la erradicación del VIH es similar: ya tenemos un caso en el que parece que eso ha sucedido. Es una prueba de concepto”.

Este es el mensaje positivo de estos casos. “Lo que hemos aprendido”, ha dicho Anthony Fauci, director del NIAID (Instituto Nacional de Alergia y Enfermedades Infecciosas de EE UU). Esta lectura, la del aprendizaje, es algo más que una frase hecha. En el mundo del VIH hay dos asuntos que, hasta ahora, siempre se han resistido: la vacuna y la erradicación. En 30 años no se ha conseguido encontrar una solución a esos dos problemas. “Pero ahora sabemos que en el caso de la erradicación, es posible; lo que tenemos que hacer es encontrar el sistema”, dice Moreno.

El método usado con Timothy Brown no es aplicable a los 35 millones de personas con el virus que hay en el mundo. “Su curación fue una consecuencia colateral; se la encontraron al tratarle la leucemia”, insiste Berenguer. Pero puede ser un camino. “Quizá con una quimioterapia no tan fuerte, añadiéndole algo; una vacuna terapéutica, un fármaco que bloquee los receptores, un medicamento antilatencia [que obligue al virus a salir de su escondrijo para que pueda ser destruido]”, apunta Moreno.

No era pensable tratar a los pacientes con quimioterapia", afirma Juan Berenguer

Que algo se puede hacer está claro. “Que el virus haya tardado tanto en reaparecer en estos casos es elocuente. Es posible que una quimioterapia menos agresiva con antivirales tenga el mismo efecto”, indica Moreno.

Hay más líneas ya abiertas. En la 99 Asamblea de la Sociedad Norteamericana de Radiología que acaba de celebrarse en Chicago, Ekaterina Dadachova, de la facultad de Medicina Albert Einstein de la Universidad Yeshiva de Nueva York presentó una aproximación parecida, basada en radioterapia en lugar de quimioterapia. “Para combatir el VIH necesitamos un sistema que elimina las células infectadas sin dañar las no infectadas”, dijo. Y, al igual que se está intentando con el cáncer, que tiene un problema parecido, la idea es encontrar receptores celulares específicos que lleven la radiación hasta las células infectadas. Dadachova lo ha conseguido en laboratorio, con cultivos celulares, indica la revista Medical News Today. Es solo un primer paso que deberá confirmarse más adelante. Pero son signos de que algo se mueve. Aunque no sea urgente, como señala Berenguer, dada la existencia de tratamientos antivirales que consiguen unos buenos resultados en general que han permitido que la esperanza de vida de los infectados sea –salvo fracaso terapéutico- equivalente a la de otras personas de su edad, un futuro sin pastillas parece un prometedor reto al que no se quiere renunciar.

107 Source: http://sociedad.elpais.com/sociedad/2014/01/06/actualidad/1389027965_835407.html

Un paso atrás en la batalla para derrotar al Sida

Dos pacientes a los que habían dado por definitivamente curados tuvieron una recaída. Esto abre nuevos interrogantes sobre la eficacia de los tratamientos. Pero no invalida los grandes avances en la lucha contra el virus.

Tras recibir en 2007 un trasplante de médula ósea, Timothy Brown se convirtió en el primer hombre del mundo en haberse curado del HIV. Las células madre que le trasplantaron en un hospital de Berlín para tratarlo por una leucemia no sólo lograron revertir su enfermedad oncológica sino que hicieron desaparecer por completo su carga viral. La esperanza de haber encontrado finalmente una alternativa terapéutica contra el virus del SIDA llevó a que cinco años más tarde un equipo médico de Boston repitiera la experiencia con otros dos pacientes, sólo que en ellos la infección acaba de reaparecer.

La noticia de su recaída, que se conoció a mitad de semana, fue como un baldazo de hielo para muchos de los investigadores que buscan alternativas terapéuticas contra el HIV. Y es que si bien nunca se pensó que los trasplantes de médula pudieran convertirse en un tratamiento aplicable a gran escala, al menos parecían un recurso efectivo para algunas personas que sufren esta enfermedad. “El regreso del virus demuestra cuán ingenioso puede ser el HIV para hallar zonas del organismo donde esconderse y evadir los esfuerzos por atacarlo del sistema inmune y de los tratamientos farmacológicos”.

Además de tener el virus de la inmunodeficiencia humana, los pacientes de Boston padecían de un tipo de cáncer sanguíneo denominado linfoma, por el cual habían sido tratados con trasplantes medulares, uno en 2008 y el otro en 2010. Pero a diferencia del paciente de Berlín, las células madre que les fueron trasplantadas carecían de una rara mutación genética que se conoce como Delta 32 y que al parecer confieren resistencia al HIV.

Pese a ello, sus médicos esperaban que las nuevas células encontraran la forma de matar tanto a las cancerosas como a las infectadas con el virus de la inmunodeficiencia humana. Y así pareció al principio: aún cuando ambos pacientes habían dejado de tomar antiretrovirales luego del trasplante (uno durante siete meses y otro durante 15) no parecía quedar en su cuerpo ningún rastro de la infección... hasta que a fin de año ésta volvió a asomar. Si bien los reportes médicos indican que ambos pacientes se encuentran “en buen estado de salud” y ya retomaron la terapia antirretrovirales, el desenlace de sus experiencias significa un rotundo punto final para esa línea de investigación.

108 RESERVORIOS PROFUNDOS La reaparición de la enfermedad en los pacientes de Boston constituye una prueba de que en su caso el VIH nunca se fue. Como explican los investigadores, el tratamiento contra la leucemia resultó lo suficientemente agresivo para diezmar al virus al punto en volverlo imperceptible, pero no acabó con él en forma total.

Y es que basta que quede una sola célula infectada para que comience a infectar a las demás. “El regreso del virus demuestra cuán ingenioso puede ser el VIH para hallar zonas del organismo donde esconderse y evadir los esfuerzos por atacarlo del sistema inmune y de los tratamientos farmacológicos”, dice Timothy Henrich, el médico responsable de supervisar la experiencia de Boston, para quien su resultado, aunque decepcionante, no sería en este sentido por completo desalentador.

“A través de esta investigación hemos descubierto que el reservorio del VIH es más profundo y más duradero de lo que creíamos anteriormente y que nuestros estándares actuales de evaluación del virus no serían suficiente”, señala el investigador del Hospital Brigham de Boston. “Sin duda es un revés para los pacientes, pero un avance para el campo científico porque nos ha permitido contar ahora con más información”, dice Steven Deeks, especialista en VIH de la Universidad de California, quien coincide con Henrich en que “el principal mensaje práctico de estas recaídas es que las pruebas para detectar incluso pequeños niveles de VIH presentes en el cuerpo no son lo suficientemente sensibles”. ¿Podría sin embargo este fracaso ofrecer algún tipo de aporte a la búsqueda de una cura a la enfermedad? Por lo pronto tampoco los trasplantes de médula constituían una verdadera solución, señalan los infectólogos. Y es que pretender tratar a las casi 35 millones de personas que padecen HIV en el mundo con un método tan poco disponible, complejo y peligroso, resultaba desde el principio una alternativa totalmente inviable.

“TOTALMENTE INVIABLE” “Aun cuando hubiera resultado exitoso, el experimento que hizo el grupo de Boston ofrecía un universo terapéutico muy restringido: personas con indicación de trasplante de médula pero además en condiciones de recibir un tratamiento que implica la destrucción de todos sus glóbulos blancos, algo muy peligroso y por lo cual uno se puede morir”, señala el doctor Jorge Cueto, director del Centro de Referencia del Programa VIH-SIDA en La Plata.

“En un momento en que los tratamientos disponibles contra el HIV permiten vivir con la enfermedad, y en la mayoría de los casos no exigen más que tomar una pastilla al día, pensar en un trasplante de médula como alternativa terapéutica es un verdadero disparate. Y no sólo porque los trasplantes resultan complejos y costosos sino además porque conllevan un riesgo de muerte considerable”, coincide en destacar el doctor Amadeo Esposto, jefe del Servicio de Infectología del Hospital San Martín.

En ese sentido -dice el infectólogo, la experiencia de Boston, que ha sido muy comentada en todos los Congresos, sólo se explica como un intento por estudiar mecanismos que eventualmente podrían derivar en una alternativa terapéutica innovadora, pero no como una opción terapéutica en sí”. “Mientras se trabaja para desarrollar una vacuna, la lucha contra el HIV pasa esencialmente por someterse al test universal para saber quién está enfermo y no seguir contagiando, y por lograr que todas las personas enfermas

109 estén bajo tratamiento de manera que vaya disminuyendo la carga viral en la comunidad. Lo otro, que dos pacientes trasplantados hayan tenido una mejoría -sostiene Esposto-, no pasa de ser una anécdota aunque el intento hubiera salido bien”.

Source: http://www.eldia.com.ar/edis/20140105/Un-paso-atras-batalla-para-derrotar-Sida-tapa5.htm

Le VIH peut disparaître et réapparaître

9 décembre 2013

Le VIH peut se cacher pendant un temps dans des «compartiments» de l’organisme, puis réapparaître. «C’est décevant mais très important sur le plan scientifique», soulignent les chercheurs physiciens du département des maladies infectieuses au Brigham and Women’s Hospital de Boston. Ainsi, deux patients séropositifs étaient atteints d’une forme de cancer du sang qui nécessitait une greffe de moelle osseuse. Près de huit mois après leurs opérations respectives, le VIH avait disparu de leurs analyses. Sa réapparition indique que «les réservoirs du VIH sont plus profonds que ce que nous croyions», répètent les chercheurs. Et que les méthodes pour détecter les infimes signes du VIH sont encore insuffisantes.

Source: http://www.liberation.fr/vous/2013/12/09/le-vih-peut-disparaitre-et-reapparaitre_965344

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L'Hiv riapparso nei pazienti di Boston. "Ci aiuterà a capire il virus" Dopo un trapianto di midollo osseo sembrava essere scomparso dal sangue di due pazienti americani. Cure anti-retrovirali sospese, ma dopo alcuni mesi i test hanno rilevato la presenza dell'Hiv. "Un insuccesso, ma una scoperta significativa per la scienza", spiegano i ricercatori del Brigham and Women's Hospital.

Timothy Henrich, ricercatore del Brigham and Women's Hospital L'HIV è in grado di diventare invisibile. E' quanto è emerso dall'esperienza di due malati di Boston, in cui per diverse settimane i test del sangue avevano escluso la presenza del virus. Una caratteristica subdola della quale ancora si ignorava l'esistenza e che rende la lotta all'Aids ancora più ardua. Secondo il parere dei medici, però, questa vicenda può diventare una scoperta cruciale per combattere il virus.

I due pazienti di Boston, oltre ad essere sieropositivi, erano affetti da un linfoma: per curarlo i ricercatori delBrigham and Women's Hospital scelsero di ricorrere a un trapianto di midollo osseo. Tra il 2008 e il 2010 entrambi subirono l'operazione. Circa otto mesi dopo il trapianto, oltre alla scomparsa del linfoma, i medici non riscontrarono più la presenza nel sangue del virus Hiv. I test sembravano confermare che il virus era stato sconfitto, proprio grazie al trapianto di midollo osseo. All'inizio del 2013 i medici decisero di sospendere la cura di farmaci anti-retrovirali e dichiararono curati i due pazienti di Boston.

Ad agosto, però, la brutta notizia. In uno dei due il virus era riapparso, 12 settimane dopo l'interruzione delle cure. E a novembre i test confermarono la ricomparsa dell'hiv nel sangue del secondo dei pazienti di Boston. "Il ritorno dell'Hiv su livelli rivelabili è una delusione, ma anche un'importante scoperta dal punto di vista scientifico", spiega il dottor Timothy Henrich, un ricercatore del Brigham and Women's Hospital. "Abbiamo dimostrato che il virus agisce in maniera più profonda di quanto pensavamo prima. Adesso sappiamo che i nostri test non sono in grado di rilevare correttamente la completa scomparsa del virus e che l'Hiv può resistere in 'serbatoi' esterni ai vasi sanguigni".

Il caso dei pazienti di Boston può essere quindi un punto di partenza per lo sviluppo di test più affidabili e di nuove tecniche per la cura del virus. Il sistema immunitario sembrerebbe poter giocare un ruolo importante nella riduzione delle riserve di Hiv, ma non può fare tutto da solo. Con una combinazione di farmaci e terapie, si potrebbe intaccare anche quelle riserve più nascoste e più persistenti di cui prima si ignorava l'esistenza e che ora diventano l'aspetto su cui indagare.

Source: http://www.repubblica.it/salute/ricerca/2014/01/02/news/hiv_pazienti_boston-74980844

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HIV returns in two Boston patients thought to be cleared of virus

In a disappointing setback in the search for a cure, two men who had stopped taking antiretroviral drugs after bone marrow transplants appeared to clear HIV from their bodies have both seen the virus return, the lead researcher of the ongoing study announced.

BY TRACY MILLER / NEW YORK DAILY NEWS FRIDAY, DECEMBER 6, 2013

Timothy Henrich of the Harvard-affiliated Brigham and Women's Hospital in Boston announced that HIV has returned in two patients researchers hoped were permanently cleared of the virus. The two men had received bone marrow transplants to treat blood cancer, which also seemed to wipe HIV from their systems.

Two men whom Boston researchers reported in July had been cleared of HIV after receiving bone marrow transplants have had the virus return, the lead researcher announced Thursday.

The patients, both of whom had been living with HIV for years, had each received bone marrow transplants several years ago to treat the blood cancer lymphoma. The treatment appeared to have made HIV retreat to undetectable levels in their blood.

RELATED: STEM CELL TRANSPLANTS WIPE OUT HIV IN TWO MEN: RESEARCHERS At the time of the announcement in July, one man had been off antiretroviral drugs for 15 weeks and the other for seven weeks.

But the virus returned in one patient in August and the other patient in November, said Dr. Timothy Heinrich, infectious diseases associate physician at Brigham and Women's Hospital, the Boston Globe first reported. Both have since resumed taking HIV medication.

RELATED: BABY BORN WITH HIV, NOW 3, IN 'CLEAR REMISSION,' NEW TESTS SHOW Speaking at an international AIDS research conference in Florida, Heinrich said he was announcing the preliminary developments because other scientists around the world are basing their research off his team's findings.

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SCIEPRO/GETTY IMAGES/BRAND X Only one patient worldwide is currently thought to be in permanent remission from HIV.

“We felt it would be scientifically unfair to not let people know how things are going, especially for potential patients,” Henrich said, according to the Boston Globe.

RELATED: VACCINE CURED MONKEYS OF AIDS-CAUSING VIRUS: SCIENTISTS Bone marrow transplants are risky and not considered a viable approach to treating HIV in all patients, Heinrich told the Globe in an interview. But studying its effects in select cases has furthered understanding of the way HIV works in the body. The only patient believed to have been cured of HIV, Timothy Ray Brown, received a bone marrow transplant in 2007, along with heavy doses of chemotherapy and radiation, to treat leukemia. The 47-year-old Brown, dubbed "the Berlin patient," was treated in Germany with marrow from a donor who had a rare genetic mutation that seems to make people resistant to HIV. The Boston patients' transplant did not include the mutation, known as CCR5-delta32.

RELATED: EARLY DETECTION COULD LEAD TO AIDS CURE In findings reported this year, scientists announced cautious optimism that a 3-year-old girl from Mississippi who was infected with AIDS in the womb has been put into permanent remission.

In spite of the recent disappointment, the Boston researchers continue to study the two patients and intend to widen the scope of the study to include other HIV patients with bone marrow transplants, Heinrich said.

“It’s exciting science, even if it’s not the outcome we would have liked,” he told the Globe.

Source: http://www.nydailynews.com/life-style/health/hiv-returns-boston-patients-thought-cleared-article- 1.1540158#ixzz2rnpiQrrA

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HIV Treatment > Search for a Cure HIV Re-emerges in Boston Bone Marrow Transplant Patients

Details Category: Search for a Cure Published on Thursday, 12 December 2013 00:00 Written by Liz Highleyman

Timothy Henrich (Photo: Liz Highleyman)

Two bone marrow stem cell recipients who had undetectable HIV according to the most sensitive tests for months after an experimental antiretroviral therapy (ART) interruption have experienced viral rebound and had to restart treatment, frustrating hopes for a functional cure, according to a report at the 6th International Workshop on HIV Persistence during Therapy last week in Miami.

Timothy Henrich and Daniel Kuritzkes from Brigham and Women’s Hospital first reported at the 2012 International AIDS Conferencethat 2 Boston men with HIV who had received donor stem cell transplants to treat lymphoma had no detectable traces of the virus.

Unlike the Berlin Patient, Timothy Brown, these patients received donor stem cells that were susceptible to HIV infection. Brown's donor had a double CCR5-delta-32 mutation, meaning those stem cells did not express the CCR5 co-receptor that most strains of HIV use to enter cells. Brown, who had leukemia, received an intensive chemotherapy and radiation conditioning regimen to kill off his diseased immune cells so that the donor stem cells could reconstitute a new immune system. He stopped ART at the time of transplantation and remains free of viable HIV 6 years later.

While the Boston patients received normal stem cells, they themselves were CCR5-delta-32 heterozygous, meaning they had a single copy of the protective mutation. In contrast to the potent chemotherapy Brown received, these men used a milder conditioning regimen and were able to stay on ART throughout the transplant process. After maintaining undetectable HIV according to the most sensitive tests for a few years, they underwent analytic ART interruption with frequent monitoring.

At the International AIDS Society this past summer, Henrich reported that the men continued to have undetectable plasma HIV RNA as well as undetectable integrated HIV DNA in peripheral blood mononuclear cells after 7 and 15 weeks off treatment. This finding raised hopes that some aspect of the stem cell transplant process -- other than resistant donor cells, which is difficult to replicate -- might lead to a functional cure, or the ability to maintain viral suppression without disease progression in the absence of ART.

However, as first described last week in the Boston Globe, Henrich reported at the Persistence Workshop that HIV had come back in both men. The first patient showed signs of HIV re-emergence in August, just a month after the IAS conference. The other, who opted to stay off ART, continued to appear HIV-free for 8 months, at which point he too experienced viral rebound. Both men have since restarted antiretroviral treatment and are doing well.

114 This re-emergence, Henrich said, indicates that the virus is able to hide in reservoirs in the body where researchers have difficulty finding it using existing tools. He noted that it is still unclear what led to the prolonged post-transplant suppression, or why one man was able to hold off its return significantly longer than the other.

As described in an abstract presented at the Miami meeting, Henrich's team used data from the 2 men in a mathematical model to estimate the residual latent reservoir of virus in host cells, in an effort to predict how many infected cells may remain after stem cell transplantation and how long patients should be monitored after ART interruption. After 8 and 15 weeks off therapy, "there is high probability that the patients’ total reservoir sizes are less than 15,000 and 6000 cells, respectively," they concluded. "Residual latent reservoirs may be present, but at levels orders of magnitude below the limit of detection of experimental assays necessitating other methods to estimate viral rebound probabilities and times."

Henrich's team has not yet completed their analysis of these patients, and are expected to present further details at the Conference on Retroviruses and Opportunistic Infections (CROI) next March in Boston.

While these results are disappointing, cure researcher Steven Deeks from the University of California at San Francisco told the Globe than the Boston patients "dramatically advanced the cure research agenda."

12/12/13

References

T Henrich. Challenges and Strategies Towards Functional Cure: How Low Do You Need To Go. 6th International Workshop on HIV Persistence during Therapy. Miami, December 3-6, 2013. Abstract 45.

T Henrich, E Hanhauser, L Harrison, et al. CCR5-delta-32 Heterozygosity and HIV-1 DNA Reservoir Size in Individuals on Suppressive Antiretroviral Therapy. 6th International Workshop on HIV Persistence during Therapy. Miami, December 3-6, 2013. Abstract 94.

T Henrich, AL Hill, E Goldstein, et al. Mathematical Modeling of HIV-1 Latent Reservoir Dynamics Following Hematopoietic Stem Cell Transplantation. 6th International Workshop on HIV Persistence during Therapy. Miami, December 3-6, 2013. Abstract 130.

Other Source

K Lazar. HIV virus returns after cure hope rose. Boston Globe. December 6, 2013

Source: http://www.hivandhepatitis.com/hiv-treatment/hiv-cure/4445-hiv-re-emerges-in-boston-bone-marrow- transplant-patients

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