DOCSLIB.ORG

Px Wire: on HIV Prevention Research Volume 3 | No

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Px Wire: on HIV Prevention Research Volume 3 | No A Quarterly Update Px Wire: on HIV Prevention Research Volume 3 | No. 1 January–March 2010 Despite disappointing results, there is still much to AVAC’s Take be learned from this trial. Spanning four years and four countries—South Africa, Tanzania, Uganda and Zambia— The last three months of 2009 took us to an unprecedented MDP 301 can serve as a model for future HIV prevention place in the field of HIV prevention research. For the first trials. In addition to critical scientific information, it will time in history, a clinical trial showed that the prevention provide important data from its extensive social science of HIV through vaccination is possible. Researchers also component and lessons from the comprehensive discovered the first new neutralizing antibodies in over a community engagement and preparation undertaken decade that may be helpful in the creation of new vaccine by the trial staff. candidates. At the same time, news from microbicide and MDP 301 also underscores the need to continue the PrEP trials provided reminders of the challenges and search for new laboratory assays and animal models for complexities of biomedical HIV prevention trials. assessing safety and finding correlates of protective efficacy In the broader world of HIV/AIDS, the US government in humans. In both animal studies and the laboratory, repealed the decades-long bans on federal funding for Continues on back syringe exchange and on entry to the US for people with HIV. Both of these moves represent important steps forward for evidence-based HIV prevention. Looking ahead in 2010, we anticipate a cascade of safety At a Glance and adherence data from oral PrEP trials; results from a phase IIb trial of tenofovir gel; the launch of new trials • In October, the US National Institute of Allergy and looking at intermittent PrEP and the “test-and-treat” Infectious Diseases (NIAID) held a workshop, Beyond strategy; and other events we can’t predict. We hope you’ll 2010: Gaps, Challenges, and Priorities for the Future of continue to join with AVAC as we navigate what promises Preclinical PrEP, to discuss opportunities, challenges to be an exciting year together. and priorities related to the development and discovery of new PrEP agents. The two-day meeting featured presentations from Data Dispatch drug development and animal research scientists geared toward defining the target product profile PRO 2000: The final word for new PrEP agents, identifying priority areas for Last December, the Microbicides Development Programme investigation in animal models, and establishing a (MDP) released results from the microbicide trial MDP 301. research agenda around correlates of protection. The trial showed that PRO 2000 (0.5%) gel is safe but not effective in reducing women’s risk of HIV infection during • In December, AVAC collaborated with amfAR in vaginal sex. Analysis of the trial data found no difference in convening a special scientific think tank on rates of HIV infection between the PRO 2000 and placebo intermittent PrEP research. This meeting considered arms—a 4.1 percent rate in the PRO 2000 arm compared both biomedical and social science elements of a to a 4.0 percent rate in the placebo arm. The unambiguous results from the trial give a definitive answer that PRO 2000 developing intermittent PrEP research agenda. is not a viable microbicide. 2010 Trial Milestones to Watch* 1st Quarter 2nd Quarter 3rd Quarter 4th Quarter Launch of HPTN 066, phase I trial to Launch of HPTN 065 TNT-Plus, a study Results from CAPRISA 004, phase IIb trial Results from IAVI’s phase I/II trials evaluate the pharmacokinetics of to evaluate the feasibility of an enhanced to evaluate the safety and effectiveness of to evaluate the safety, acceptability, intermittent oral TDF/FTC (US) “test-and-treat” approach for the 1% tenofovir gel to prevent HIV infection adherence and drug levels of oral TDF/FTC prevention of HIV transmission (US) in women (South Africa) taken once daily vs. intermittently by Results from CDC 4323, phase II trial (US) men and women (Kenya, Uganda) Launch of HPTN 067, phase I/II feasibility trial to evaluate the behavioral aspects of Completion of CDC 4940 (TDF2) (Botswana) fixed interval vs. coitally dependent PRE-EXPOSURE PROPHYLAXIS (PrEP) intermittent oral TDF/FTC in women and Completion of CDC 4370, phase II/III PARTNER TREATMENT MSM (Thailand and select African (Thailand) MICROBICIDE countries) Results expected first quarter 2011. * Trial start- and end-dates are estimates—dates may change. Additional efficacy trials and details are available on the timeline inside. Trials listed on the timeline are subject to interim analyses during the year. A Quarterly Update Px Wire: on HIV Prevention Research Volume 3 | No. 1 January–March 2010 Australia ONGOING TRIALS OF NEW PREVENTION OPTIONS WORLDWIDE Belgium Botswana Brazil Canada Sweden China Canada Russia United Kingdom Dominican Republic Belgium Germany Ecuador France Switzerland France United States China Germany Dominican Republic Haiti Haiti Jamaica Puerto Rico India India Thailand Jamaica Kenya Uganda Malawi Ecuador Kenya Rwanda Peru Tanzania Peru Brazil Puerto Rico Zambia Malawi Russia Zimbabwe Botswana Australia Rwanda South Africa South Africa Sweden Switzerland Tanzania Thailand Uganda United Kingdom United States Zambia Zimbabwe VACCINES MICROBICIDES PRE-EXPOSURE PROPHYLAXIS (PrEP) PrEP & MICROBICIDE PARTNER TREATMENT BIOMEDICAL HIV PREVENTION RESEARCH: A COMPREHENSIVE TIMELINE OF EFFICACY TRIAL RESULTS* 2007 2008 2009 2010 2011 2012+ CONRAD CELLULOSE SULFATE HSV-2 SUPPRESSION (HPTN 039) HPTN 035 CDC 4323 iPrEx PARTNERS PrEP Phase III trial to evaluate the effect Phase III trial to evaluate suppressive Phase II/IIb trial to evaluate the Phase II trial to evaluate the clinical Phase III trial to evaluate the safety Phase III trial to evaluate the safety of cellulose sulfate gel on vaginal HIV acyclovir treatment for the reduction safety and effectiveness of the and behavioral safety of once-daily and efficacy of once-daily oral and efficacy of two different strate- transmission in women (Benin, India, of HIV infection in HSV-2 seropositive vaginal microbicides, BufferGel and oral TDF among men who have sex TDF/FTC to prevent HIV infection gies to prevent HIV transmission in South Africa, Uganda, Zimbabwe) women and men who have sex with 0.5% PRO 2000/5 gel, to prevent HIV with men (US) among men who have sex with men HIV-serodiscordant couples: once- Trial stopped early. No evidence of men (Peru, South Africa, US, Zambia, infection in women (Malawi, South Release of results expected February (Brazil, Ecuador, Peru, South Africa, daily oral TDF and once-daily oral benefit. There were more infections Zimbabwe) Africa, US, Zambia, Zimbabwe) 2010. Thailand, US) TDF/FTC (Kenya, Uganda) among women using the gel than No evidence of benefit. There were fewer infections in women those using placebo, but this was not using PRO 2000 than women using CAPRISA 004 FEM-PrEP statistically significant. MALE CIRCUMCISION IN HIV- the placebo gel, but this difference Phase IIb trial to evaluate the safety Phase III trial to evaluate the safety POSITIVE MEN was not statistically significant. No and effectiveness of 1% tenofovir gel and effectiveness of once-daily FHI CELLULOSE SULFATE Large-scale trial to evaluate the evidence of benefit in women using to prevent HIV infection in women oral TDF/FTC for HIV prevention in Phase III trial to evaluate the safety safety of male circumcision and BufferGel. (South Africa) women (Kenya, Malawi, South Africa, and effectiveness of cellulose sulfate its potential protective effect for Release of results expected July 2010. Tanzania, Zambia) gel to prevent HIV infection in women HIV-negative female partners of HIV- PARTNERS IN PREVENTION (Nigeria) positive circumcised males (Uganda) Phase III study to evaluate the effect CDC 4370 HVTN 505 Trial stopped following announce- Trial stopped enrollment, December of suppressive acyclovir treatment Phase II/III trial to evaluate the safety Phase II test-of-concept trial to ment of data from CONRAD trial. No 2006. No statistically significant con- for HSV-2 on HIV transmission in and efficacy of once-daily oral TDF evaluate the safety and effect on evidence of safety concerns or of clusions could be drawn from sample HIV-serodiscordant couples to prevent HIV infection in injecting post-HIV infection viral load of the effectiveness. size. However, men who resumed sex (Botswana, Kenya, Rwanda, South drug users (Thailand) VRC’s DNA prime / Ad5-boost vaccine prior to wound healing were more Africa, Tanzania, Uganda, Zambia) strategy in HIV-negative, Ad5-sero- MIRA likely to transmit HIV to their female No evidence of reduced rates of HIV CDC 4940 (TDF2) negative and circumcised men who Phase III trial to evaluate effective- partners. transmission, but there were reduced Phase II trial to evaluate the safety of have sex with men (US) ness of the female diaphragm to rates of genital ulcers and HIV once-daily oral TDF/FTC in prevent HIV infection (South Africa, CARRAGUARD viral load. heterosexual men and women VOICE (MTN-003) Zimbabwe) Phase III trial to evaluate the safety (Botswana) Phase IIb trial to evaluate the safety No evidence of benefit. and efficacy of the vaginal micro- ALVAC-AIDSVAX (RV 144) and effectiveness of three different bicide Carraguard to prevent HIV Phase III trial to evaluate the safety strategies to prevent HIV in women: STEP (HVTN 502/Merck 023) infection in women (South Africa) and efficacy of a prime-boost vac- once-daily oral TDF, once-daily oral Phase IIb test-of-concept trial to No evidence of benefit. cine strategy (ALVAC plus AIDSVAX) TDF/FTC, and 1% tenofovir gel (South evaluate safety and efficacy of to prevent HIV infection (Thailand) Africa, Uganda, Zambia, Zimbabwe) Merck’s Ad5 candidate (Australia, Initial data show that vaccine Brazil, Canada, Dom. Rep., Haiti, recipients were 31% less likely than HPTN 052 Jamaica, Peru, Puerto Rico, US) placebo recipients to become HIV- Phase III trial to evaluate the ef- Trial halted immunizations, September infected.
Load more

Recommended publications
  • RESEARCH a Forum for Putting Knowledge Into Practice July 2008 Volume 2, Issue 2
    FAMILY HEALTH RESEARCH A forum for putting knowledge into practice JULY 2008 VOLUME 2, ISSUE 2 INSIDE 2 Clinical research update 4 Evaluating tenofovir gel in South Africa 6 Participating in microbicide trials 7 Preparing for microbicides 8 Research and advocacy partnerships sub-Saharan Africa still suffers the most from MICROBICIDES the epidemic. More than two-thirds of all HIV- FOR HIV infected people in the world live in this region. Of these, more than 60 percent are women. PREVENTION Young women are even more disproportion- ately affected. In South Africa, for example, This issue describes efforts to develop women make up 90 percent of the HIV- a safe, effective, and acceptable vaginal infected population of 15- to 24-year-olds. microbicide to prevent HIV. Women are at especially high risk of HIV Scientists around the world are working infection because of biologic susceptibility, diligently to develop new ways to prevent HIV, economic dependence on male partners, including vaccines, pre-exposure prophylaxis and inability to negotiate condom use within (when drugs normally used to treat HIV are all of their sexual relationships. A method of used for prevention), and topical microbicides. HIV prevention that a woman could control, Advocacy and support for prevention research such as a vaginal microbicide, could help are strong, and the availability of an effective overcome some of these inequities and save product—although likely years away—could many lives. help alleviate the HIV epidemic in sub-Saharan Africa and worldwide. An effective microbicide could be a powerful addition to current efforts to protect against The Joint United Nations Programme on HIV, including abstinence, mutual monog- HIV/AIDS recently announced that the preva- amy with uninfected partners, condom use, lence of HIV has stabilized or declined in many treatment of sexually transmitted infections, parts of sub-Saharan Africa.
    [Show full text]
  • Next Steps 1% Tenofovir Gel
    DRAFT Next steps 1% Tenofovir Gel Meeting report Johannesburg, South Africa 25–26 August 2010 Department of Reproductive Health and Research Next Steps with 1% Tenofovir Gel Meeting Report Johannesburg, South Africa 25‐26 August 2010 23 November 2010 Next Steps with 1% Tenofovir Gel WHO/UNAIDS Meeting Report 13 January 2011 ii Next Steps with 1% Tenofovir Gel WHO/UNAIDS Meeting Report 13 January 2011 Executive Summary The results of the CAPRISA 004 trial, released in July 2010, showed that 1% tenofovir gel reduced the risk of HIV infection in women by 39% compared with placebo, and by 54% in the women who reported more consistent gel use. These results were historic. After nearly two decades of research,s thi was the first clinical trial to show that a vaginal microbicide could provide a safe and effective way to prevent sexual transmission of HIV. The gel also provided a 51% protective effect against herpes simplex virus type 2 infection (HSV‐2). The announcement raised questions about the most appropriate next steps: making the gel available to women at risk based on this single trial; planning and implementing additional trials to confirm the results; or waiting for the results of the VOICE (Vaginal and Oral Interventions to Control the Epidemic) trial, another trial of 1% tenofovir gel using a different dosing strategy. To identify priority next steps, WHO and UNAIDS convened a meeting on 25‐26 August 2010 that drew together more than 80 diverse stakeholders from a range of countries. The meeting, hosted by the South African Department
    [Show full text]
  • PMPA Gel (TMC120) (N=2) TOTAL “51” (N=2) Discovery/Early Preclinical “44” Advanced Preclinical “7”
    Moving Forward with ART Based Microbicides Sharon L. Hillier, Ph.D. University of Pittsburgh School of Medicine OVERVIEW: The Microbicide Pipeline Clinical Development (for HIV) Preclinical Discovery Preclinical Virology Studies 1 2 3 •ACIDFORM™/ •Carraguard Preclinical Development Amphora™ •PRO 2000 •PC 815 (N=2) • Vaginal defense enhancers 6 •UC-781 • Surface-active /membrane-disruption •VivaGel™/ agents 1 SPL7013 (N=4) • Entry/fusion inhibitors 33 1/2 • Replication inhibitors 2 2B • Combinations 8 •Invisible •BufferGel® Condom™ •Tenofovir/ • Uncharacterized mechanism 1 •Dapivirine PMPA gel (TMC120) (N=2) TOTAL “51” (N=2) Discovery/early preclinical “44” Advanced preclinical “7” Source: Alliance for Microbicide Development, 9 April 2007 MTN Portfolio Years 1and 2 Study Products Design HPTN-035 PRO-2000, BufferGel Phase 2/2B HPTN-059 Tenofovir (PMPA gel) Phase 2 MTN-004 VivaGel Phase 1 MTN-001 TDF (oral), tenofovir (PMPA Phase 2 gel) MTN-003 TDF, tenofovir gel, ± Phase 2B Truvada MTN-002 Tenofovir Phase 1-pregnant women MTN-015 Seroconverter Protocol Observational ARTs as Topical Microbicides • TMC-120 (Dapavirine): available as gel and ring; being developed by the International partnership for microbicides • PMPA gel (Tenofovir): available as a gel; being development by CONRAD • MIV150: available as gel, just entering phase 1 testing; being developed by the Population Council Redefining The Road to Success for Microbicides in 2007 • More focus on highly potent inhibitors of HIV • Enhance assessment of safety in animal models and tissue explants • Add more assessments of safety in new trials of microbicides • Move toward coitally independent use of microbicides Tenofovir Mechanism • Acyclic nucleoside analog of AMP. • Requires hydrolysis to form tenofovir diphosphate.
    [Show full text]
  • Vaginal Microbicides for Reducing the Risk of Sexual Acquisition of HIV
    Obiero et al. BMC Infectious Diseases 2012, 12:289 http://www.biomedcentral.com/1471-2334/12/289 RESEARCH ARTICLE Open Access Vaginal microbicides for reducing the risk of sexual acquisition of HIV infection in women: systematic review and meta-analysis Jael Obiero1,2*, Peter G Mwethera1, Gregory D Hussey3,4 and Charles S Wiysonge3,4 Abstract Background: Each year more than two million people are newly infected with HIV worldwide, a majority of them through unprotected vaginal sex. More than half of new infections in adults occur in women. Male condoms and male circumcision reduce the risk of HIV acquisition; but the uptake of these methods is out of the control of women. We therefore aimed to determine the effectiveness of vaginal microbicides (a potential female-controlled method) for prevention of sexual acquisition of HIV in women. Methods: We conducted a comprehensive search of peer-reviewed and grey literature for publications of randomised controlled trials available by September 2012. We screened search outputs, selected studies, assessed risk of bias, and extracted data in duplicate; resolving differences by discussion and consensus. Results: We identified 13 eligible trials that compared vaginal microbicides to placebo. These studies enrolled 35,905 sexually active HIV-negative women between 1996 and 2011; in Benin, Cameroon, Cote d’Ivoire, Ghana, Kenya, Malawi, Nigeria, South Africa, Tanzania, Uganda, Zambia, Zimbabwe, India, Thailand, and the United States of America. A small trial of 889 women found that tenofovir (a nucleotide reverse transcriptase inhibitor) significantly reduces the risk of HIV acquisition (risk ratio [RR] 0.63, 95% confidence intervals [CI] 0.43 to 0.93).
    [Show full text]
  • What Happens Next: Understanding the Results of HPTN 035 and MDP 301 and the Promise of Arvs for HIV Prevention
    CONTACT: Lisa Rossi PHONE: +1- 412-641-8940 +1- 412- 916-3315 (mobile) E-MAIL: [email protected] What Happens Next: Understanding the Results of HPTN 035 and MDP 301 and the Promise of ARVs for HIV Prevention SUMMARY • Both MDP 301 and HPTN 035 were well-designed and well-executed studies that answered the scientific questions they were designed to answer. HPTN 035 was an intermediate-sized study designed to determine the safety of PRO 2000 and BufferGel and establish whether either product showed sufficient promise for further testing in a Phase III trial or for licensure. It found that PRO 2000 was safe and reduced the risk of HIV by 30 percent, a finding that, although encouraging, was not statistically significant – the odds are one in 10 that the result was due to chance rather than to the product itself. As such, HPTN 035 indicated the need for more research. As a Phase III study involving nearly 9,400 women, MDP 301 was designed to give a more definitive answer about PRO 2000, which it did, finding PRO 2000 was safe but not protective against HIV. While these findings are a disappointment, it is important to understand that research is informed just as much from studies with disappointing outcomes as those considered breakthroughs. • By no means do these studies represent the final act. Other promising approaches are being investigated, most notably, those involving antiretrovirals (ARVs). Because ARVs are effective for treatment of HIV there is good reason to think they can work to prevent HIV infection as well.
    [Show full text]
  • Rectal Microbicides: Can We Make Them and Will People Use Them?
    AIDS Behav DOI 10.1007/s10461-011-9899-9 ORIGINAL PAPER Rectal Microbicides: Can We Make Them and Will People Use Them? Ian McGowan Ó Springer Science+Business Media, LLC 2011 Abstract The results of the CAPRISA 004 and iPrEx transmitted infections (STIs) including HIV [1]. The ori- HIV prevention studies have demonstrated that topical or ginal impetus for vaginal microbicide development was to systemic use of antiretroviral agents can significantly provide women with options for HIV prevention in settings reduce the risk of HIV acquisition associated with unpro- where their partners were unwilling to use condoms [2]. tected vaginal or anal sexual intercourse. However, the Years later, the need to also develop a rectal microbicide effect size in these studies was relatively modest and (RM) became clear, given that a significant proportion of product adherence was generally poor. These observations men do not consistently use condoms during anal sex with suggest the need for new approaches to HIV prevention, men or women [3, 4], and that there has consequently been especially for high risk MSM. Rates of lubricant use are little or no decline in the rates of new HIV infections, high in MSM practicing receptive anal sex. Consequently, particularly in men who have sex with men (MSM) [5]. the development of an antiretroviral rectal microbicide gel Unprotected receptive anal intercourse (RAI) is the sexual may provide a safe and effective means of preventing HIV behavior with the highest per act risk of HIV acquisition, infection with an intervention that is likely to have high conferring perhaps 10–20 times more risk than unprotected acceptability among the target population.
    [Show full text]
  • Hptn 035 Q&A
    CONTACT: Lisa Rossi PHONE: +1-412-641-8940 +1-412- 916-3315 (mobile) E-MAIL: [email protected] EMBARGOED FOR MONDAY, FEB. 9 AT 8:30 AM EASTERN/ 3:30 PM AFRICA QUESTIONS AND ANSWERS HPTN 035: A MULTI-CENTER CLINICAL TRIAL EVALUATING THE CANDIDATE MICROBICIDES BUFFERGEL AND PRO 2000 FOR PREVENTION OF HIV 1. What was the aim of HPTN 035? HPTN 035 was a multi-center clinical trial that evaluated the safety and effectiveness of two candidate microbicides, BufferGel® and PRO 2000 (0.5 percent dose) for preventing male-to-female sexual transmission of HIV. 2. What is a microbicide? Microbicides are substances that are intended to reduce or prevent the sexual transmission of HIV and other sexually transmitted infections when applied topically inside of the vagina or rectum. A microbicide can be formulated in many ways, such as a gel or cream or in a vaginal ring. Several candidate microbicides are being tested in clinical trials, although none is yet approved or available for use. 3. Who conducted and funded the study? HPTN 035 was conducted by a team of leading African and U.S. researchers associated with the Microbicide Trials Network (MTN), an HIV/AIDS clinical trials network established and funded in 2006 by the National Institute of Allergy and Infectious Diseases (NIAID), with co-funding by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), all components of the U.S. National Institutes of Health (NIH). Prior to the establishment of the MTN, the study was conducted by the NIAID-funded HIV Prevention Trials Network (HPTN), from which the study gets its name.
    [Show full text]
  • Safety and Effectiveness of Buffergel and 0.5% PRO 2000 Gel For
    NIH Public Access Author Manuscript AIDS. Author manuscript; available in PMC 2012 April 24. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: AIDS. 2011 April 24; 25(7): 957±966. doi:10.1097/QAD.0b013e32834541d9. Safety and Effectiveness of BufferGel and 0.5% PRO2000 Gel for the Prevention of HIV Infection in Women Professor Salim S Abdool Karim1,2, Professor Barbra A Richardson3, Professor Gita Ramjee4, Professor Irving F Hoffman5, Professor Zvavahera M Chirenje6, Professor Taha Taha7, Dr Muzala Kapina8, Dr Lisa Maslankowski9, Ms Anne Coletti10, Dr Albert Profy11, Dr Thomas R. Moench12, Ms Estelle Piwowar-Manning13, Professor Benoît Mâsse14, Professor Sharon L. Hillier15, and Dr Lydia Soto-Torres16 on behalf of the HPTN 035 Study Team 1 Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, South Africa 2 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA 3 Department of Biostatistics, University of Washington, USA 4 HIV Prevention Research Unit, South African Medical Research Council, South Africa 5 Division of Infectious Diseases, University of North Carolina, USA 6 Department of Obstetrics and Gynecology College of Health Science, University of Zimbabwe, Zimbabwe 7 Bloomberg School of Public Health, Johns Hopkins University, USA 8 Centre for Infectious Disease Research in Zambia, Zambia 9 University of Pennsylvania, USA 10 Family Health International, USA 11 Preclinical and Pharmaceutical Sciences, Endo Pharmaceuticals Solutions, USA 12 ReProtect Inc, Baltimore, Maryland, USA 13 Johns Hopkins University, USA 14 University of Montreal, Canada 15 University of Pittsburgh School of Medicine, USA 16 National Institutes of Health, USA Corresponding and reprint author: Salim S.
    [Show full text]
  • Microbicides for HIV Prevention
    FAMILY HEALTH RESEARCH A forum for putting knowledge into practice JULY 2008 VOLUME 2, ISSUE 2 INSIDE 2 Clinical research update 4 Evaluating tenofovir gel in South Africa 6 Participating in microbicide trials 7 Preparing for microbicides 8 Research and advocacy partnerships infected people in the world live in this region. MICROBICIDES Of these, more than 60 percent are women. FOR HIV Young women are even more disproportion- ately affected. In South Africa, for example, PREVENTION women make up 90 percent of the HIV- infected population of 15- to 24-year-olds. This issue describes efforts to develop a safe, effective, and acceptable Women are at especially high risk of HIV microbicide to prevent HIV. infection because of biologic susceptibility, economic dependence on male partners, and Scientists around the world are working dili- inability to negotiate condom use within all gently to develop new ways to prevent HIV, of their sexual relationships. A method of HIV including vaccines, pre-exposure prophylaxis prevention that a woman could control, such (when drugs normally used to treat HIV are as a topical microbicide, could help overcome used for prevention), and topical microbi- some of these inequities and save many lives. cides. Advocacy and support for prevention research are strong, and the availability of Both vaginal microbicides (for use by an effective product—although likely years women) and rectal microbicides (for use by away—could help alleviate the HIV epidemic women and men) are under development. in sub-Saharan Africa and worldwide. This issue will focus on the vaginal products that have reached clinical trials of effective- The Joint United Nations Programme on HIV/ ness in humans.
    [Show full text]
  • CAPRISA 004 Phase Iib Trial to Assess the Safety and Effectiveness
    CAPRISA 004 Phase IIb Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel for the Prevention of HIV Infection in Women in South Africa Trial design and conduct: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa, Coordination of Product manufacture and packaging: CONRAD, Virginia, USA Statistical, regulatory and operational support: Family Health International, North Carolina, USA Co-Principal Investigators Quarraisha Abdool Karim, PhD, and Salim S. Abdool Karim, MBChB, PhD CAPRISA, University of KwaZulu-Natal Version 1.3, 29 October 2010 CAPRISA 004 - Version 1.3 Page 1 29 October 2010 Phase IIb trial to assess the safety and effectiveness of the vaginal 1% tenofovir gel for the prevention of HIV infection in women in South Africa PROTOCOL TEAM ROSTER Quarraisha Abdool Karim, PhD Salim S. Abdool Karim, MBChB, FFPHM, PhD Co-Principal Investigator Co-Principal Investigator CAPRISA, Nelson R Mandela School of Medicine, CAPRISA, Nelson R Mandela School of Medicine, University of KwaZulu-Natal , Private Bag 7, University of KwaZulu-Natal, Private Bag 7, Congella 4013, Durban, South Africa Congella 4013, Durban, South Africa [email protected] [email protected] T: 27-31-260 4208 T: 27-31-260 2381 F: 27-31-260 4307 F: 27-31-260 3093 Cheryl Baxter, MSc Janet Frohlich, DipMGC, DCurVulindlela Site Research Associate Operations ManagerCAPRISA Vulindlela Clinical CAPRISA , Nelson R Mandela School of Medicine, Research Site, Mafakatini Primary
    [Show full text]
  • 1 PRO2000 Vaginal Gel for the Prevention of HIV Infection
    PRO2000 vaginal gel for the prevention of HIV infection: results of the MDP301 Phase III randomised microbicide trial Sheena McCormack MSc MRC Clinical Trials Unit, London UK Gita Ramjee PhD MRC HIV Prevention Research Unit, Durban, South Africa Anatoli Kamali MSc MRC/UVRI Uganda Research Unit, Entebbe, Uganda Helen Rees MRCGP RHRU, University of the Witwatersrand, Johannesburg, South Africa Angela Crook PhD MRC Clinical Trials Unit, London UK Mitzy Gafos MSc Africa Centre for Health and Population Studies, South Africa Ute Jentsch PhD CLS, University of the Witwatersrand, Johannesburg, South Africa Robert Pool PhD University of Barcelona, Barcelona, Spain & University of Amsterdam, The Netherlands Maureen Chisembele MBBS University Teaching Hospital, Lusaka, Zambia Saidi Kapiga MD Mwanza Intervention Trials Unit (MITU), Mwanza, Tanzania Richard Mutemwa PhD London School of Hygiene and Tropical Medicine, London, UK Andrew Vallely PhD London School of Hygiene and Tropical Medicine, London, UK Thesla Palanee PhD RHRU, University of the Witwatersrand, Johannesburg, South Africa Yuki Sookrajh MBChB MRC HIV Prevention Research Unit, Durban, South Africa Charles J Lacey MD University of York, UK Janet Darbyshire MSc MRC Clinical Trials Unit, London UK Heiner Grosskurth PhD MRC/UVRI Uganda Research Unit, Entebbe, Uganda Albert Profy PhD Endo Pharmaceuticals Solutions, Inc., Chadds Ford, Pennsylvania, USA Andrew Nunn MSc MRC Clinical Trials Unit, London UK Richard Hayes DSc London School of Hygiene and Tropical Medicine, London, UK Jonathan Weber PhD Imperial College, London, UK Address for Correspondence Dr Sheena McCormack MRC Clinical Trials Unit 222 Euston Road London, NW1 2DA, UK Tel: +44 2076704703 1 Abstract Background: There is an urgent need for effective HIV prevention strategies such as vaginal microbicides that can be used by women.
    [Show full text]
  • Preparing for Access to PRO 2000 Microbicide
    WHO/RHR/10.19 Preparing for access to PRO 2000 microbicide Report of a meeting 27–28 May 2009, London, United Kingdom World Health Organization and UNAIDS Meeting report Meeting report Contents Acknowledgements 3 Executive summary 3 Acronyms and abbreviations 4 Background 5 What do (and can) we know about PRO 2000 from the HPTN 035 and MDP 301 trials? 6 Safety and effectiveness 6 Further studies and analyses 6 Acceptability and users’ perspectives 6 Additional clinical research 7 Product ownership and licensing 7 Cost 8 Manufacturing 8 Regulatory review 9 Carcinogenicity study 10 Policy and programmes 10 Level of effectiveness 10 Modelling 11 Donors 12 WHO recommendations 12 Implications for other prevention trials 13 Strategic communications and messaging 13 Scientists 14 Policy-makers 14 Trial communities 14 Next steps 14 Appendix 1: Contingency planning list for PRO 2000 access 15 Appendix 2: Timeline for PRO 2000 access 21 Appendix 3: List of participants 22 Preparing for access to PRO 2000 microbicide Note: Since this report was prepared, the results of the MDP 301 study were announced on 14 December 2009 and published in The Lancet on 20 September 2010. (http://dx.doi.org/10.1016/S0140-6736(10)61086-0). The study showed no benefit of 0.5% PRO2000 in reducing the risk of HIV infection. All further development and investment in the product has ceased. Preparing for access to PRO 2000 microbicide © World Health Organization 2010 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]).
    [Show full text]