A Quarterly Update Px Wire: on HIV Prevention Research Volume 1 | No. 4 October–December 2008 and Phambili studies. The initial results of the Step study AVAC’s Take were published in November 2008 in the Lancet journal (Lancet, doi:10.1016/S0140-6736(08)61591-3). Greetings! This is the last issue of Px Wire in 2008—and what In the Step study, MRK-Ad5 had no overall benefit in terms a year it has been. The AIDS vaccine field has started to move Continues on back ahead with different goals and refined strategies in the wake of disappointing data from 2007. Multiple PrEP trials were launched or expanded, the microbicide field began to focus considerably At a Glance: Moving right along more on the implications of ARV-containing products, and the scale-up of male circumcision started in some countries. • An FDA panel of independent advisors recommended At the International AIDS Conference in August, and approval of the newly formulated female condom (FC2) in a provocative Lancet article (Lancet, doi:10.1016/S0140- in December, green-lighting the less expensive and 6736(08)61697-9) by WHO staff, including Kevin De Cock, physically streamlined second-generation product by director of the HIV/AIDS program, the notion of ARV the Female Health Company. Donors, governments and treatment as prevention seized the spotlight. This newly implementers should take advantage of this lower cost highlighted strategy will continue, we predict, to help shape option and take long overdue action to dramatically the field in 2009. increase access to and information about the female Also in 2009, AVAC will work with other prevention stakeholders condom as part of all HIV prevention and family to put the spotlight on HIV testing, which is the cornerstone planning programs. for almost all of the new and emerging prevention strategies. As we continue the search for new options, it’s imperative that • The Phase III clinical trial “Partners in Prevention” testing programs continue to expand in ways that are innova- completed all study visits in November 2008 and the data tive, responsive to community priorities, and sustainable. are now being analyzed. The study sought to determine In 2008, the best work that’s happened has been through whether suppressing HSV-2 in HIV-positive people reduced efforts that brought scientists and communities together in the risk of passing HIV to their HIV-negative partners. conversations that haven’t always been easy but have always The study enrolled 3,000 serodiscordant heterosexual been important. We’ve been honored to be part of these couples. The HIV-positive partners were randomized to conversations—and look forward to having many more of receive ongoing acyclovir (HSV-2 treatment) or a placebo. them in the year to come. Public release of data from the trial is anticipated Warmest wishes, in mid-2009. AVAC • In November, a Data and Safety Monitoring Board Data Dispatch: HVTN 505 conducted a scheduled safety review of the phase IIb CAPRISA 004 tenofovir gel microbicide study and For the past few months, the US-based conversation around recommended that the trial continue. The study aims to vaccine research has kept circling back to a trial now known determine whether the use of the gel can help prevent as HVTN 505. male-to-female vaginal transmission of HIV. The study In brief, HVTN 505 is a proposed “exploratory” study by is enrolling 930 women in South Africa and is expected the NIH-funded HIV Vaccine Trials Network (HVTN) to test a to be completed in 2010. vaccine strategy developed by the US Vaccine Research Center. The strategy to be tested consists of two different vaccines. • The iPrEx study of oral tenofovir+emtricitabine (TDF/ The first three immunizations are with a DNA “prime” that FTC) has begun enrolling volunteers at trial sites in Brazil. stimulates anti-HIV immunity. The prime also prepares the The study is evaluating the safety and effectiveness of TDF/ immune system for the “boost,” a single immunization that FTC as oral pre-exposure prophylaxis (PrEP) in roughly consists of synthetic fragments of HIV packaged into a disabled 3,000 HIV-negative gay men and other men who have cold virus known as adenovirus serotype 5, or Ad5. sex with men. In addition to sites in Brazil, the study is Ad5 may ring some bells with Px Wire readers. A similar, though enrolling volunteers in Ecuador, Peru, South Africa and not identical, form of this cold virus was used in the Merck the United States. It will begin enrolling volunteers in vaccine candidate, MRK-Ad5, which was evaluated in the Step Thailand in early 2009. Results are expected in late 2010. A Quarterly Update Px Wire: on HIV Prevention Research Volume 1 | No. 4 October–December 2008 ONGOING TRIALS OF NEW PREVENTION OPTIONS WORLDWIDE Australia Belgium Botswana Brazil Canada Sweden China Canada Russia United Kingdom Germany Dominican Republic Belgium France Switzerland Ecuador United States France China Dominican Republic Germany Haiti Haiti Jamaica India Puerto Rico India Thailand Jamaica Kenya Uganda Malawi Ecuador Kenya Rwanda Peru Tanzania Peru Brazil Zambia Puerto Rico 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 HSV-2 TREATMENT PARTNER TREATMENT New New New New New HIV PREVENTION RESEARCH: A COMPREHENSIVE TIMELINE OF EFFICACY TRIALS* 2007 2008 2009 2010 2011 2012+ FHI Phase III trial of the vaginal Phase III trial of acyclovir for the Study of different risk-reduction Large-scale efficacy trial of a once- Large-scale efficacy trial of a Large-scale efficacy trial to determine microbicide Cellulose Sulfate gel reduction of HIV infection in high-risk, interventions for HIV vaccine trials— daily dose of oral tenofovir to prevent once-daily dose of oral tenofovir+ the effectiveness of two different for the prevention of HIV infection HIV-negative, HSV-2 seropositive Project UNITY (US) HIV infection in injecting drug users emtricitabine to prevent HIV infection HIV prevention strategies; once-daily in women (Nigeria) individuals (Peru, South Africa, US, (Thailand) in heterosexual men and women oral tenofovir and once-daily oral Zambia, Zimbabwe) (Botswana) tenofovir+emtricitabine in serodis- Phase II/IIb trial of the vaginal Trial stopped early–January 2007 cordant heterosexual couples microbicides BufferGel and 0.5% Results announced July 2007 Results announced February 2008 Large-scale efficacy trial of a (Kenya, Uganda) PRO 2000/5 gel for the prevention once-daily dose of oral tenofovir+ Phase III trial of community of HIV infection in women (Malawi, emtricitabine to prevent HIV infection mobilization, mobile testing, same- South Africa, Tanzania, US, Zambia, CONRAD Phase III trial of the vaginal Large-scale trial to evaluate the in high-risk men who have sex with day results, and post-test support Phase III trial to determine the Zimbabwe) microbicide Cellulose Sulfate gel safety of male circumcision and men (Brazil, Ecuador, Peru, South for HIV (South Africa, Tanzania, effectiveness of two antiretroviral for the prevention of HIV infection in its potential protective effect for Africa, US) Thailand, Zimbabwe) treatment strategies in preventing the sexual transmission of HIV in women (Benin, India, South Africa, HIV-negative female partners of HIV- Phase III trial of HSV-2 suppression HIV-serodiscordant couples (Brazil, Uganda, Zimbabwe) positive circumcised males (Uganda) in serodiscordant couples (Botswana, India, Malawi, Thailand, US, Zimbabwe) Kenya, Rwanda, South Africa, Phase IIB trial of the vaginal Trial stopped early January 2007 Trial stopped enrollment and Tanzania, Uganda, Zambia) microbicide tenofovir gel for the Results announced July 2007 surgeries in December 2006. prevention of HIV infection in women Results announced February 2008 (South Africa) Phase III trial of the vaginal microbi- Phase III trial of the female dia- cide PRO 2000 for the prevention of phragm to prevent HIV infection in Phase III trial of the vaginal microbi- HIV infection in women (South Africa, women (South Africa, Zimbabwe) cide Carraguard for the prevention of Tanzania, Uganda) HIV infection in women (South Africa) Results announced July 2007 Results announced February 2008 Phase III trial of a prime-boost (ALVAC-AIDSVAX) combination VACCINE CERVICAL BARRIER METHOD Test-of-concept trial of Merck’s preventive HIV vaccine (Thailand) adenovirus preventive HIV vaccine candidate—STEP study (Australia, PRE-EXPOSURE PROPHYLAXIS (PrEP) PARTNER TREATMENT Brazil, Canada, Dom. Rep., Haiti, Phase II trial to test the clinical and HERPES SIMPLEX VIRUS 2 (HSV -2) Jamaica, Peru, Puerto Rico, US) BEHAVIORAL behavioral safety of a once-daily dose TREATMENT/SUPPRESSION of oral tenofovir among HIV-negative Trial halted immunizations, men who have sex with men (US) MICROBICIDE September 2007. Follow-up and data collection continue. MALE CIRCUMCISION TRIAL COMPLETED OR STOPPED Test-of-concept trial of Merck’s adenovirus preventive HIV vaccine To view this timeline online with trial details please visit www.avac.org/timeline-website/. candidate—Phambili (South Africa) * The trial end-dates listed in this table are estimates. Due to the nature of clinical trials the actual dates may Trial halted enrollment and immu- change. AVAC will continue to monitor the trials’ progress and will update the timeline accordingly. nizations, September 2007. Follow-up and data collection If you have any questions or comments regarding the information presented here please email [email protected]. continue. Px Wire: A Quarterly Update on HIV Prevention Research | Volume 1 | No.4 | October–December 2008 | Data Dispatch continued from p.1 Coming Up: New Trials of reducing viral load set point or the risk of HIV infection. The vaccine also appeared to increase the risk of acquiring HIV in a subset of male volunteers with very specific • FEM-PrEP, a study to assess the effectiveness of a once-daily characteristics (uncircumcised, and having previous exposure TDF/FTC pill in preventing HIV in women is slated to to Ad5 as measured by antibodies to Ad5).