HIV/AIDS Interventions in Developing Countries: Guiding Policy and Action Ccording to the UNAIDS 2006 Into Associated Costs and Consequences

Volume 4 Issue 1 SPOTLIGHT Summer/Spring 2006

Focus: HIV/AIDS Interventions in Developing Countries: Guiding Policy and Action ccording to the UNAIDS 2006 into associated costs and consequences. A Report on the Global AIDS Epi- These data can be used as planning and as- demic, almost $8.9 billion has sessment tools which can provide national been allocated to finance the global re- governments and financial partners with sponse to AIDS. This funding falls short of critical information on how to maximize the needed $14.9 billion for this year alone. health benefits through a mix of prevention Maximizing the limited funding is one of and treatment program components. the many challenges that developing coun- The conference focused on key policy is- tries, which share the greatest burden of the sues and programmatic constraints that 38.6 million people living with HIV/AIDS were addressed in five topic areas: identify- in the world, must face. ing cost savings and synergies of HIV pre- Health economics researchers, policy vention and treatment, using economic makers, and major international donors evaluation to guide policy and action, ex- gathered together to examine these and ploring the linkages between macroeco- Photograph by S. Camarata other issues at the “HIV/AIDS Interven- nomic to microeconomic impacts, examin- Policy makers (pictured here Diane Thompson tions in Developing Countries: Using Cost ing the impact of businesses on the AIDS and Peter Piot) emphasize the need for re- Benefit and Cost Effectiveness Analysis to crisis, and investigating the transportability searchers to present cost effectiveness and cost Guide Policy and Action” conference, of costing techniques to ensure the ability benefit analyses in relevant terms for affecting which was held from September 13-15 in to generalize results. policy decisions. Boston. Participants discussed and debat- Conference participants framed their re- ed the intricate economic, social, and pro- search positions by citing findings and ex- the Joint United Nations Programme on grammatic concerns that impact compre- amples from costing and cost effectiveness HIV/AIDS, Jim Kim of the Harvard School hensive HIV/AIDS care, particularly in the studies conducted in India, Thailand, South of Public Health, Diane Thompson of the context of limited health systems and oper- Africa, Nigeria, Mexico, and Botswana. Rec- Elizabeth Glaser Pediatric AIDS Founda- ational capacities. These concerns continue ommendations on how economics can in- tion, and Yves Souteyrand of the World to gain worldwide attention because gov- form practical program implementation de- Health Organization. ernments and donors require efficient fiscal cisions and general policy questions on all Joy Phumaphi, assistant director - gener- accountability for program implementa- levels were also raised. al of the Family and Community Health di- tion and scale-up procedures. A way to The conference program included open vision at the World Health Organization of- measure economical expenditures is by discussion sessions in which issues that fered suggestions to researchers on what using cost effectiveness analysis (CEA) and might impede progress and affect long-term tools they can provide to public policy mak- cost benefit analysis (CBA). planning processes were discussed. A panel ers. Phumaphi said, “The key areas where CEA and CBA are methods health econ- of representatives from local and interna- we need a lot of direction are linking differ- omists use to identify where the most ab- tional governments and policy agencies ent models of assessment and evaluation of sorptive capacity exists in healthcare, com- fielded these concerns and offered opinions programs in the critical areas that impact munity, public, and private settings. These on useful strategies in working within these HIV/AIDS and development. So that the methods also provide evidence based sugges- constraints. Representatives included Joy models we are currently developing for tions for what steps should be taken to effi- Phumaphi of the World Health Organiza- human resources, planning, analyzing ciently scale-up capacity in particular re- tion, Loeto Mazhani of the Botswana Min- strategic information, cost benefit models gions. CEA uses models that can capture the istry of Health, Robert Oelrichs of the for assessing whether to invest in a program processes and decisions associated with pre- World Bank, Dan Kress of the Bill & Melin- or scale it up and how to strengthen it – how vention and treatment, especially when clin- da Gates Foundation, Joseph O’Neill of Im- you link all these together in order to enable ical data is unavailable, and translates them mune Response Corporation, Peter Piot of a decision maker (continued on back page)

VViieewwppooiinnttss A Discussion with Mr. Richard Smith and Dr. Max Essex cide how best to treat these patients avail- thirds, if the drug is administered four-to-six able. They are available in selective ways and weeks before delivery. The mother-to-infant in a few places, Botswana being one of the transmission rate can be further reduced if most advanced. But there is still a lack of another class of drugs are used at the time of education about how to use them in most delivery, but the problem of drug resistance countries for both the patient and clinician. then arises. The same drugs that help preg- The situation, though, is getting better be- nant HIV-positive mothers prevent transmis- cause now many countries in Africa with sion may be needed later to treat their own good governmental systems have begun to disease, and their prior use greatly increase

. Ng address the epidemic. the chance that they won’t be effective for treatment due to drug resistance. RS: Is there something about the virus, the science of HIV/AIDS, that leads to the In places like Botswana 35% of pregnant Photograph by Y high-risk in Africa? What makes Africa women are HIV-positive and 30-40% of in- Richard Smith and Dr. Max Essex ground zero? fants born to those women become infected if drugs are not used to prevent transmis- ME: The viruses in Africa that cause sion. That means one out of every six or On a warm April evening, HSPH Leader- HIV are wholly different from the viruses in eight children born in Botswana or Swazi- ship Council member Irene Weigel and HAI In- the US and Europe. The main virus that is land will be infected if nothing is done, so ternational Advisory Council member Susan causing HIV in the US and Western Europe it is really important to treat them, but by Curren, hosted an intimate discussion group. is called subtype B and although subtype B the same note we have got to develop new The conversation topic, The Continuing is present in Africa in very low numbers, it systems to keep the mothers alive so the in- AIDS Crisis--Does the Answer Lie in Africa?, is one of the least virulent on the continent. fants do not all become orphans. was led by HAI International Advisory Coun- cil member, Chairman, Editor-in-Chief, and The virus in southern Africa, which is RS: I well remember a [Newsweek] cover Chief Executive Officer of Newsweek, Richard HIV 1-C, is undoubtedly more virulent that we did about five or six years ago on Smith and HAI’s Dr. Max Essex. The follow- than other forms of the virus because the AIDS in Africa, and the line on the cover was ing is an excerpt of the dialogue that took place. transmissibility rates of the other viruses in 10 million orphans. I feel that number is a

RS: Max to start with, as far as HIV/AIDS is concerned in the developed "I really believe that we will have a vaccine in 10 or 20 years. Twenty years is a world, this is no longer the kind of auto- long time and we have to figure out what to do until then, but when we do I think matic death sentence that it has been for so we’ll also have built a solution, through the results of how to make vaccines, to a many years. And yet in the developing lot of different diseases, like herpes and some cancers.” world the disease rages on. What is hap- pening right in the developed world, and - Dr. Max Essex why is the problem still an enormous one in the developing world? East Africa or West Africa are not as high. low number now. Talk about the scale that The medical dictionary defines virulence as we’re looking at here in the AIDS epidemic. ME: I think a good breakthrough in the transmissibility and how quickly it kills. Al- West was the recognition of three-drug though there is no evidence that the virus in ME: That certainly is a low number now. combinations. These expensive drugs could southern Africa kills faster, there is evidence There are about 40 million people living readily save people and there was a lot of that it is transmitted more efficiently. with HIV/AIDS and two-thirds of these dedication to using them. Major efforts people live in sub-Saharan Africa. There is were made to educate people for getting RS: Let’s talk about the mother-child a movement to treat a lot more people liv- tested and to find out whether or not their transmission issue. To me, it is one of the ing with the virus. About a million people status was positive and help those people bright spots in the work that is going on. have now been treated with antiretroviral who needed drugs. drugs in Africa. That’s a start and I think it ME: There has been a lot of progress. will be 2 or 3 million in another year and 4 In the case for the developing world, Clearly by using just one relatively inexpen- or 5 million and 6 million in a few years but those very expensive drugs still aren’t wide- sive drug, zidovudine, you can reduce trans- we will need to cope with the inevitable ly available, nor are the tests required to de- missions from mother to infant by two- newly emerging drug resistance problem. I

International Clinical Research Training

The Fogarty / Ellison Overseas Fellowship ty will strengthen students’ commitment to in Global Health and Clinical Research is in a future career in global health. its fourth year, accepting applications from With a highly valued mentoring compo- highly qualified graduate-level students in nent, the Fellowship ensures that each par- health fields across the U.S. ticipant is matched with both a researcher at Each year, the Fellowship, supported by the foreign site and a faculty member from the Fogarty International Center and the El- the US institution, in this case HAI. Fur- lison Medical Foundation, along with the thermore, each U.S. fellow is matched with

National Institute of Allergy and Infectious a peer fellow from the foreign institution. Photograph by BHP Diseases and the National Institute on Drug In Botswana, Fogarty/Ellison fellows At the BHP, the Fogarty/Ellison Overseas Fel- Abuse, provides 25 to 30 future health care work at the Princess Marina Hospital, men- low serves as part of the Tshedimoso Team professionals with the opportunity to devel- tored by members of the Botswana–Har- op clinical research skills in the unique set- vard School of Public Health AIDS Initia- ease. This year’s fellow, Carl Davis, a Har- ting of a developing nation. Fellows have tive Partnership for HIV Research and Ed- vard College, Class of 2000 summa cum the opportunity to train in National Insti- ucation (BHP) and are matched with peers laude graduate and now a candidate for tutes of Health-funded research institutions training in the Botswana health system. MD, PhD, from University of Pennsylva- in Africa, Asia, and the Americas. Site coun- For three years, fellows working with nia School of Medicine, and David Nkwe tries include Bangladesh, Botswana, Brazil, the BHP have been interacting directly his matching Botswana fellow, will both China, Haiti, India, Kenya, Mali, Peru, with a population living with the work on the acute HIV infection study. South Africa, Russia, Tanzania, Thailand, HIV/AIDS epidemic and learning crucial The deadline for submitting an application Uganda, and Zambia. The Fellowship’s or- research techniques firsthand in order to is December 8, 2006. More information ganizers hope that this one-year opportuni- further clinical knowledge about the dis- can be found at http://aids.harvard.edu. News & Events

Enhancing AIDS Care and Treatment Study revealed that infants who received zi- feasible, acceptable, and safe should exclu- The Enhancing Care Initiative of the West- dovudine while breastfeeding from HIV-in- sively formula feed their children to prevent ern Region of Puerto Rico published an ar- fected women had higher rates of HIV in- transmission of HIV. ticle in the June edition of the American fection but lower rates of death and illness. Journal of Public Health. The team present- However, formula feeding to prevent postna- New HIV Vaccine Partnership ed the results of their Needs Assessment tal HIV transmission was associated with Founded in March 2005 by HSPH col- which examined the HIV/AIDS services in higher rates of mortality, with severe pneu- league Dr. Yichen Lu, the Haikou VTI Bi- the region. monia and diarrhea, especially in HIV-in- ology Institute’s mission is to advance the Two main findings of the assessment fected children (although lower rates of HIV field of vaccinology through vaccine re- were that depression symptoms were pres- transmission to infants). Overall, very similar search and development, the production of ent in 98.1% of people living with proportions of breastfed and formula-fed in- vectors and cells for use in human gene ther- HIV/AIDS, and that 7 of 15 municipalities fants remained alive and HIV-negative. apy clinical trials, and the production of di- in the region did not provide any specific Although additional research is needed agnostic kits. Institute scientists, based in services to this population. Furthermore, to try and find effective ways of preventing the west coast of the Haikou City of Hainan the most urgent needs identified by people HIV transmission through breastfeeding, Island in China, are working on new flu vac- living with HIV/AIDS were economic sup- these findings should cause HIV-infected cines and new treatments for malaria. The port, housing, mental and psychological mothers in developing countries to exercise Institute’s expertise in vaccine development services, medicines, medical treatment, and extreme caution in using formula feeding. coupled with existing HIV-1 subtype C vac- transportation. As a result, the Enhancing Breastfeeding from HIV positive mothers cine development efforts at the Care Initiative has planned two major in- still appears to provide important antibody Botswana–Harvard Partnership will further terventions to address services coordination protection for the infant against common a joint HIV vaccine development program and mental health. bacteria and viruses. The World Health Or- for southern Africa. ganization will be considering these and other Sign up for free email updates! Breast Versus Formula Feeding: findings in a potential revision of their infant Sign-up to receive free email updates from HAI. Overall Outcomes Similar feeding guidelines for HIV-infected women. Simply send an email to [email protected] In the August 16th issue of the Journal of the The current guidelines recommend that HIV- to receive electronic news and details about up- American Medical Association, the Mashi infected women for whom formula feeding is coming events.

Focus: HIV/AIDS Interventions in Developing Countries (cont. from front page)

to use all the information and apply it cor- results. Accessible language and common The Harvard-wide international confer- rectly to make a decision – I think this is the terminology for both researchers and poli- ence was made possible with support and area where there is a gap. Also, we are talk- cy makers should be used and sustained partnership of our sponsors: The Bill & ing about scaling up and moving to univer- during the research investigation process. A Melinda Gates Foundation, Elizabeth sal access, but the big question is the rate at clear explanation of how funding would be Glaser Pediatric AIDS Foundation, Fogar- which you can scale up given the resources used is essential in emphasizing the cost ef- ty International Training Program in that are available. And what levels of invest- fectiveness of an initiative. AIDS-related Epidemiology, Harvard ment would be required to attain certain Researchers and panel members strongly School of Public Health, HAI, Harvard rates of scale up of programs. This is ab- agreed that both parties should work to- University Centers for AIDS Research, solutely critical now. Otherwise the rate of gether hand in hand throughout the re- Harvard University Program on AIDS, scale up is determined by when the next search and program planning process. This Joint United Nations Programme on election is going to be.” would be one of the most effective ways to HIV/AIDS, The Merck Company Founda- Panel members suggested that research advance AIDS policy and action. The par- tion, National Institute of Mental Health, questions should be framed in locally ap- ticipants will expand upon the discussions World Bank, World Health Organization. propriate context with methods that can be and recommendations through the publica- To learn more about the program, please employed to ensure the transportability of tion of a journal supplement, due next year. visit http://www.aids.harvard.edu.

SPOTLIGHT is published by the Research & Intervention Programs (cont. from page 3) Harvard School of Public Health AIDS Initiative 651 Huntington Avenue, 6th Floor Reaching a Stigmatized Population in method to target this group. The team Boston, MA 02115 USA Phone: 617-432-4400 Botswana found that using anthropological tech- Fax: 617-432-4545 niques was most effective. This practice in- Email: [email protected] One of the most vulnerable populations in Web: aids.harvard.edu the AIDS epidemic is illegal drug users. Al- cludes defining locations for making con- Chair: Max Essex though, doubly stigmatized because of their tact, emphasizing confidentiality, and Senior Research & Executive Director: Richard Marlink addiction and their HIV positive status, identifying liaisons from the community to PUBLICATIONS STAFF these individuals may provide important in- inform potential participants in a discreet Editor: Yvonne Ng Print Designer: Kim Morrisseau formation on how HIV affects their immune manner. Potential study participants were Contributing Writers: Jenifer Brown, Patricia Burns, system. The challenge for researchers is re- reassured that no criminal charges would Erika Fardig, Leah Gordon, Molly Pretorious Holme, Elizabeth Jackson, Saidi Kapiga, Amina Khawja, cruiting drug abusers for a clinical trial. be pressed by police nor would they expe- Shahin Lockman, Yichen Lu, Vlad Novitsky rience any retaliation from others within Through a collaboration with the BHP, The efforts of HAI depend very much on your sup- HAI, University of Miami, and Florida In- their community. This recruitment port. Contributions to the HAI are tax deductible. method could serve as a model for other To learn more, please call Michael Voligny at ternational University, researchers were 617-384-8980.

able to devise an innovative recruiting studies trying to reach this group.

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think this is a serious problem that is going who want to go to places like Botswana and nia can go to the Botswana lab to learn tech- to be present in Africa for a long, long time spend a year or two participating in and niques and then return to their country with unless we find a better solution than just running these trials. That has worked to that new training. drug treatment such as a successful vaccine everyone's advantage. or other biological means of prevention. Recently we were asked by the Southern In the spring of 2007, we're going to African Development Community, an or- RS: You and your colleagues across the start a program for Harvard undergraduates ganization of 14 countries in southern board have been working 15 years, why who will spend a semester in Botswana for Africa, to put on a week-long HIV/AIDS haven’t we seen one by now? academic credit. They'll spend time in our training course for parliamentarians, who lab here in Boston, then spend a semester on ultimately decide on how to allocate re- ME: HIV is a very special pathogen and a research project in Botswana and also take sources for their national HIV/AIDS pro- one of the reasons why it develops drug re- a course or two in African history or lan- grams. This will be a tremendous opportu- sistance so quickly is the same reason that it guages at the university there. nity to give the educational tools to leading is very difficult to make a vaccine. This virus government officials who can directly affect mutates faster than any other virus. It has RS: One of the things that really im- the health of their people. qualities that make it more difficult to cope pressed me about HAI is that the research is with than other viruses, even Avian flu. tied to treatment on the ground. Obviously RS: A lot of grant money is devoted to lab- This tremendous rate of genomic variation for all the sophistication that allows you to oratory research, and less to training programs or virus evolution is what causes the prob- do the research and all of that there is an and the kind of research examining treatment lem for developing a vaccine. enormous human need in much less sophis- programs that set HAI apart from everything ticated places. Talk about how you help on else. What do you need to get more of the The stage that vaccine research is at now the treatment side as well. kind of work you're doing done? is in modeling the three-dimensional structure of the unfolded surface of the virus at ME: Well, I should speak about Dr. ME: It's hard to find money to train the time it attaches to two cell receptors Richard Marlink, who is a senior member of AIDS experts from most countries in Africa. with a hope that stabilizing the unfolded the BHP team. He developed a Botswana- We managed to put together a program structure would allow you to induce im- based HIV/AIDS program to train physi- with people from Botswana, but we don't mune responses to block attachment. This cians and nurses in AIDS treatment and have money specifically to train people from is the stage that develops solid infection. care. More than 900 physicians and 4,000 Zambia or Malawi, for example. And there But this is a whole new generation of mak- nurses have completed various courses on are a lot of people in those countries who’ll ing vaccines, obviously anything we did how to use AIDS medications. These health need training if they are to make the kind of with any of the other infectious diseases did- practitioners can now write prescriptions for progress Botswana is making. n’t come close to that level of sophistication. government supplied anti-retroviral AIDS drugs. And I think that sort of teaching I really believe that we will have a vaccine makes a significant difference because it in 10 or 20 years. Twenty years is a long time helps reach more people living with How You Can Help... and we have to figure out what to do until HIV/AIDS who need their medications. The Initiative’s efforts depend upon your then, but when we do I think we’ll also have support. Contributions are tax deductible. built a solution, through the results of how RS: Botswana is the epicenter of the To make your contribution to HAI online, to make vaccines, to a lot of different dis- HIV/AIDS crisis on the continent and the please visit the Harvard School of Public eases, like herpes and some cancers. One home of your research center. What ele- Health giving page at can view HIV research as building and in- ments of the Botswana model are you try- http://www.hsph.harvard.edu/give/. forming the general field of vaccinology. ing to push out to the rest of Africa and to Checks can be made payable to the Asia, India, China, with their growing prob- Harvard School of Public Health AIDS RS: The HAI approach involves real col- lem? What will you do to encourage that Initiative and sent to: laboration with the Botswana government, movement to other countries? Harvard School of Public Health not only in terms of informing them, but in AIDS Initiative training their researchers and bringing them ME: We are making available to many 651 Huntington Avenue, 6th Floor into your program. countries all the educational material used Boston, MA 02115 to train physicians and nurses. That's a start. To support HAI through gifts of securities, ME: Yes, we've been fortunate to have We are doing similar trials in several other bequests, and naming opportunities, the support to train people from Botswana. countries in other regions in Africa. We're please contact: We've also been fortunate to have bright, exchanging AIDS experts with other coun- Michael Voligny young physicians and scientists from the tries in Africa. For example, we have an ex- (617) 384-8980 email: U.S. with training in infectious diseases change program where people from Tanza- [email protected]

Research & Intervention Programs

Micronutrient Therapy be given to uninfected women to prevent than women who did not have a STI. The The Dikotlana Study aims to investigate the the acquisition and establishment of HIV if risk became even greater in women who effect of micronutrient supplementation on the woman has sexual contact with an HIV- had genital herpes, a common STI that the clinical progression of HIV to AIDS. infected man. causes frequent recurrent infections and Study participants are followed for 24 In studies conducted in human blood cell genital ulcers, which appear to enhance months and are randomized into four cultures, drug resistance to tenofovir devel- HIV transmission. The researchers con- groups: combination of multivitamins with oped in just 12 weeks if the infecting virus cluded that STIs and genital infections fa- selenium, multivitamins alone, selenium was HIV-1 subtype C, the prevailing sub- cilitated the HIV epidemic in this cohort of alone, and placebo. type of Botswana. If other viruses were in- high-risk women. The team discovered some striking initial fecting the cultures, such as HIV-1 subtype The incidence of HIV could be reduced information about the trial. Researchers B, the virus commonly found in the US, re- through the treatment of genital infections found that selenium supplementation has a sistance took a year or more to develop. The and increased consistent use of condoms. strong potential to decrease genital HIV-1 resistance with tenofovir is caused by a par- shedding. Additional study in this area ticular mutation, K65R, that develops faster could lead to new ways to delay the progres- in subtype C. However, this resistance mu- sion of HIV to AIDS, thus improving qual- tation, when it develops, also gives resistance ity of life and decreasing the financial bur- to several other drugs, such as didanosine den of ARV treatment. This discovery was (also known as DDI), lamivodine (3TC), detailed in one of the four abstracts from this and stavudine (D4T). study accepted by the 2006 International This study indicates the need to further AIDS Conference in Toronto for poster and monitor and research the development of drug resistance within HIV subtypes as well oral presentations. Photograph by S. Kapiga

The program is managed by the Florida as prepare to adjust antiretroviral treatment Bars, like the one in M & K Hollywood Restau- International University in cooperation with regimens in developing countries. This is rant, were venues considered in the study. BHP and the Botswana Ministry of Health particularly important because different sub- and is funded by the National Institute on types, such as HIV-1 subtype C, the virus of Drug Abuse. southern Africa, may have different patterns Improving Access to ART in Nigeria of drug resistance. When people living with HIV/AIDS (PLWHA) understand how their HIV drug HIV Infection in Northern Tanzania treatments help manage their HIV, they are Colleagues from HSPH, HAI, Kilimanjaro more likely to maintain their drug regi- Christian Medical Centre, International mens. This is a major finding by re- Partnership for Microbicides and other in- searchers of AIDS Alliance in Nigeria, stitutions have been conducting epidemio- AIDS Prevention Initiative in Nigeria, and logical studies to determine the rate of ex- Harvard President’s Emergency Plan for pansion of the HIV epidemic in the general AIDS Relief. This is also a significant step Photograph by A. Campa population and among high-risk groups, towards helping the growing number of Study team members collecting riverbed rocks and examine the social and biological deter- 70,000 Nigerian PLWHA now receiving from a nearby stream to place in the newly ex- minants of HIV infection. The studies will antiretroviral therapy. panded clinic’s garden. contribute valuable data which could be Basic counseling training for PLWHA used in the development of effective HIV in- to help other PLWHA has become one of Potential Drug Resistance to HIV-1 tervention programs and in the design of the most effective methods in reaching Subtype C clinical trails to test promising interventions. those within their community and also Scientists at the McGill AIDS Centre in In a study on female bar and hotel work- others who may seek treatment. Re- Canada and the BHP have detected a po- ers in Moshi, a small bustling town located searchers further found that this form of tential complication with an AIDS drug on the slopes of Mount Kilimanjaro, re- patient education provides a greater sense considered for the prevention and treatment searchers found the rate of acquisition of of responsibility and commitment on the of HIV infections in southern Africa. HIV was very high in this population, and part of PLWHA to maintain their own Tenofovir is considered to have great poten- condom use remained low. Another finding health. These efforts ultimately support tial for use in microbicides, as well as in the from this research was that women who had greater treatment adherence and fewer op- use of multiple drug regimens to treat AIDS sexually transmitted infections (STIs), had portunities for drug resistance. patients. As a microbicide, tenofovir would a higher risk of becoming HIV-infected (continued on back page)