Press Release

AVAC says results of new PrEP trials provide clear evidence that antiretroviral drugs for prevention can help end the AIDS epidemic; calls for quick action on results

New York, NY – Results from two African studies of pre-exposure prophylaxis, or PrEP, released today provide clear evidence that the antiretroviral drugs used to treat HIV can also be used to prevent HIV among heterosexual men and women at risk of HIV infection.

“These results are tremendously exciting and confirm that we are at pivotal period in the AIDS epidemic,” said Mitchell Warren, AVAC executive director. “Antiretroviral (ARV) drugs for HIV treatment began to turn the tide of the epidemic 15 years ago, and it is clear that also using ARVs for HIV prevention will strengthen our response to AIDS. PrEP, ARV-based microbicides and treatment as prevention are powerful tools to help end the cycle of new infections and end the epidemic.”

“We now have data that earlier treatment initiation in HIV-positive people can reduce risk of HIV transmission—and that use of ARVs in HIV-negative people can reduce risk of infection. There is a global imperative to act on these results without delay,” Warred added. “Now is the time to include ARV-based prevention in national plans, applications to the Global Fund to Fight AIDS, Tuberculosis and Malaria and donor priorities. We need ambitious pilot and demonstration projects to guide programmatic design, along with national and international guidance on how best to use ARVs as lifesaving prevention tools. The next steps will not be simple but they will be essential. Scientific data do not change the world—programs and policies backed by civil society, donors, implementers and governments do. The countries where PrEP trials took place should lead the way in these critical efforts.”

“We congratulate the trial sponsors, scientific collaborators and partners who conducted these trials. We especially want to thank the more than 10,000 men and women whose altruism and commitment as trial volunteers made this effort possible,” Warren said. “These volunteers and their communities have made an inestimable contribution to HIV prevention research and to the eventual development of new ways for men and women to protect themselves from HIV.”

The Partners PrEP study in Kenya and Uganda enrolled 4,758 heterosexual couples in which one partner was HIV-positive and the other HIV-negative. The trial showed that both tenofovir (TDF, marketed as Viread) and tenofovir plus emtricitabine (TDF/FTC, marketed as Truvada) taken daily can reduce the risk of HIV transmission among both men and women. In the trial, daily oral TDF reduced HIV risk by an estimated 62 percent infections (95% CI 34 to 78, p=0.0003) and daily oral TDF/FTC reduced HIV risk by an estimated 73 percent (95% CI 49 to 85, p<0.0001) when compared to a placebo. Both drugs were effective in both men and women, and there were no significant safety events in the trial.

Separately, the TDF2 study in Botswana enrolled just over 1,200 sexually active men and women. At the time of its completion, TDF2 was an expanded safety trial that was not designed to provide information on effectiveness. However, analysis of final data on numbers of infections in the active and placebo arms indicated that daily oral TDF/FTC reduced the risk of HIV infection in both men and women participants by an estimated 62.6 percent (95% CI 21.5 to 83.4, p=0.0133) compared to those who received the placebo.

AVAC looks forward to continued discussion of the meaning of these findings for men and women in different contexts. Additional data from these studies not released today, but expected over the coming months, will help guide these discussions. These include data on drug resistance from Partners PrEP, data on drug levels in blood plasma, cells and tissue samples, viral genotyping of infecting strains within Partners PrEP couples to identify linked and unlinked transmissions, and other information.

These results add to a growing body of evidence confirming the powerful potential of antiretroviral drugs for HIV prevention. This includes the positive results of the iPrEx trial, a study of daily oral TDF/FTC in gay men, other men who have sex with men, and transgender women, which showed a 44 percent reduction in HIV risk compared to placebo; CAPRISA 004, a trial of 1% tenofovir gel in heterosexual women, which showed that women who received the gel had an estimated 39 percent lower risk of infection compared to those who received an inactive placebo gel; and HPTN 052, which demonstrated a 96 percent reduction in HIV transmission among HIV serodiscordant couples when the HIV-positive partner received early antiretroviral treatment.

“At this critical juncture in biomedical prevention research, it is essential that governments, program implementers and donors move with speed to identify and enact the next steps suggested by the findings from these two trials of pre-exposure prophylaxis and from other recent successful trials,” Warren said.

Today’s findings make even more critical that stakeholders act on recommendations put forward in a statement, “We CAN End the AIDS Epidemic,” which has been endorsed by more than 30 organizations and close to 400 individuals around the world to date. Next steps should include:

Trial teams and Gilead, which donated the study drug, should ensure continued access to study drug for all participants in the Partners and TDF2 studies, including those in the placebo arms.
National governments should work with donors and program implementers to identify the implementation research needed to address unanswered questions and evaluate the potential impact of PrEP in key populations and contexts and to evaluate treatment as prevention, building on the result from HPTN 052.
At national and international levels, new findings from Partners and TDF2 as well as data from iPrEx and HPTN 052, should be integrated into ongoing strategic planning, funding proposals for the Global Fund to fight AIDS, Tuberculosis and Malaria and other processes.
National AIDS programs along with civil society and other key partners must swiftly develop clear messages for a range of audiences, including at-risk individuals and communities, program implementers, policy makers, regulators and others, about what these data mean—and what questions remain to be answered.
Funders, trial sponsors and researchers should prioritize additional research for PrEP and microbicides using different agents and mechanisms of delivery.

“Because the drugs evaluated in the Partners and TDF2 PrEP trials are licensed and available as treatment for HIV-positive people, men and women at risk of HIV infection need immediate information about what these data tell us and what questions remain. The US Centers for Disease Control and Prevention (CDC) moved quickly to provide interim guidance for PrEP use among men who have sex with men in the United States following the data from the iPrEx trial. Now CDC should move quickly to issue updated guidance for all populations in which PrEP has been shown to be effective.

At the same time, the World Health Organization (WHO) must move quickly to develop guidance for all populations for whom PrEP has now been shown to be effective,” Warren said. “And African countries, especially those where these trials took place, must also move quickly to determine the place of both PrEP using TDF/FTC or TDF, as well as earlier initiation of ARVs, in national prevention programs.”

In addition, the VOICE trial, which is looking at the use of oral PrEP and vaginal microbicides among women in several African countries, is expected to provide additional data that may help guide both PrEP and microbicide programs. “We know that the VOICE team and its independent Data and Safety Monitoring Board will be carefully reviewing the data from both of these trials and evaluating the potential impact on VOICE, and that the trial will provide critical additional information about both PrEP and tenofovir gel microbicides.” Warren said. Results from the VOICE trial are expected in 2012. Forthcoming data from the FEM-PrEP trial, which was stopped earlier this year after it was determined that the trial would not be able to provide an efficacy result, will also provide additional information about PrEP use among women.

More information is needed about issues such as adherence and possible drug resistance as well as optimal program design, integration of PrEP and earlier ART initiation into comprehensive prevention programs, and cost. Gilead announced earlier this month that it would make both drugs studied in these trials available to the UNITAID patent pool, which seeks to make generic versions of ARVs more affordable in developing countries, and which may help make PrEP more affordable.

Adherence—the ability to take PrEP as prescribed by the trial protocol—is a critical component of efficacy. Initial findings from the Partners PrEP study showed high reported adherence for the once-daily regimen. It will be important to learn why and how adherence was high in this study and what lessons can be learned for eventual rollout of PrEP. At the same time, research into intermittent dosing (e.g., weekly, semi-weekly or around the time of sex), which may be easier from some people to adhere to, is needed. Moreover, additional research is still urgently needed for other methods where adherence is less important, such as vaginal rings with monthly release, periodic injectable forms of ARVs and vaccines.

As with other HIV prevention trials, Partners and TDF2 provided a comprehensive HIV prevention package. All trial participants received condoms, safer sex counseling and treatment of sexually transmitted infections. Female participants were also provided with effective contraception. Participants were frequently tested for HIV and were intensely counseled on the importance of adhering to the daily regimen and using condoms and other prevention options—a level of counseling and testing not easily achieved outside of a clinical trial.

Demonstration projects and additional research can provide important information about how PrEP programs should be structured to account for these “real world” issues. Such projects should be prioritized and fully funded to provide answers as quickly as possible.

“As we move towards PrEP implementation, it is critical to remember that millions of HIV-positive people around the world lack access to the HIV treatment they need, which is often the same drug used in these trials,” Warren said. “We can and must find a way to ensure that PrEP is a part of comprehensive, well-funded response to HIV. That means ensuring access for all who need it to existing HIV prevention and treatment options, including universal access to treatment and care, PrEP, treatment as prevention and medical male circumcision; ensuring continued research to find and refine effective new options, including microbicides, vaccines, new and improved treatment options and a cure; and planning for integrating these new interventions into fully funded combination programs.”

More information on these and other PrEP trials can be found online at www.avac.org/prep. The sign on statement is available at endtheepidemic.org.

A PDF version of this press release is available here.

Contact:
Mitchell Warren, Mitchell@avac.org, +1-914-661-1536
Kay Marshall, kay@avac.org, +1-347-249-6375

###

About AVAC: Founded in 1995, AVAC is a non-profit organization that uses education, policy analysis, advocacy and a network of global collaborations to accelerate the ethical development and global delivery of AIDS vaccines, male circumcision, microbicides, PrEP and other emerging HIV prevention options as part of a comprehensive response to the pandemic.

Press Release

Discontinuation of the FEM-PrEP Trial Disappointing, AVAC Says; Calls for continued research to find new ways to end the HIV epidemic

New York, 18 April 2011 – At a scheduled, interim data review, the Independent Data Monitoring Committee (IDMC) for the FEM-PrEP study of oral pre-exposure prophylaxis (PrEP) using daily TDF/FTC (brand-name Truvada) determined that the trial would not be able to answer the question of whether the study drug decreased risk of HIV infection among HIV-negative women at risk via sexual transmission. The IDMC has, therefore, recommended that the study be discontinued.

“Today’s announcement about the FEM-PrEP study is disappointing,” said Mitchell Warren, AVAC executive director. “However, it must be seen as what it is – the closure of a single trial in a field that has generated exciting results in the recent past. Even with this finding, there is still a strong rationale for continuing other trials, including those in women, in hopes of obtaining better results in the future.”

The FEM-PrEP trial tested the same drug and daily dosage of TDF/FTC (also known as Truvada) as the landmark iPrEx PrEP trial among gay and bisexual men and transgender women. Last November, results of the iPrEx trial showed a 44 percent reduction in HIV risk overall in participants who received TDF/FTC compared to those who received the placebo. In July 2010, results of the CAPRISA 004 study showed a 39 percent reduction in HIV risk among women who used a 1% tenofovir gel microbicide compared to those who received a placebo gel. In both trials, there was evidence that adherence matters – that participants who used the intervention most consistently had the highest levels of protection.

Two other ongoing trials in sub-Saharan Africa are evaluating oral TDF/FTC and/or TDF alone among heterosexuals. The VOICE trial is evaluating oral TDF and TDF/FTC as well as 1% tenofovir gel in 5,000 women in sub-Saharan Africa. Partners PrEP is evaluating oral TDF and TDF/FTC in the HIV-negative member of couples in which one partner is HIV-infected.

“The premature closing from FEM-PrEP does not predict the findings from either VOICE or Partners PrEP,” Warren said. “It is too soon to tell whether the differences observed between iPrEx and FEM-PrEP are due to the route of exposure, pill-taking behavior, biological differences in drug activity, or some other factor. Along with further analysis of FEM-PrEP data, VOICE, Partners PrEP and other ongoing trials will add critical pieces to the puzzle of if and how to deploy PrEP as an effective prevention tool.”

“We commend the FEM-PrEP trial team, the members of the IDMC and especially the nearly 2,000 women who participated in the trial. Despite the inability of the trial to answer the question of whether TDF/FTC reduces women’s risk of HIV infection, FEM-PrEP has provided and will continue to provide key information that will help move the PrEP research agenda forward,” Warren said.

Further analysis of the FEM-PrEP data will provide a better of understanding of the observation that there was a higher pregnancy rate among women in the active drug arm of the trial, compared to those in placebo arm.

In addition to VOICE and Partners PrEP, there is an ongoing PrEP efficacy trial among injection drug users and a soon-to-be-launched follow-on to iPrEx known as the iPrEx Open Label Extension study, or iPrEx OLE. There are still close to 20,000 participants involved in PrEP trials around the world.

“Medical research is often complicated, and we must expect setbacks along the way. But with 2.6 million new HIV infections every year, it is imperative that we continue to look for new ways to curb the epidemic,” Warren added. “The success of the iPrEx and the CAPRISA 004 trials have shown the promise of ARV- based prevention options as part of a comprehensive prevention package that includes condoms behavioral counseling and treatment of other sexually transmitted diseases. There will never be a silver bullet for HIV prevention, so we must continue to seek a variety of new options to protect those at risk through different routes of transmission and throughout their lives.”

More information about ongoing PrEP research is available at avac.org/prep.

Contact:
Mitchell Warren, Mitchell@avac.org, +1-914-661-1536
Kay Marshall, kay@avac.org, +1-347-249-6375

###

About AVAC: Founded in 1995, AVAC is an international non-profit organization that uses education, policy analysis, advocacy, and community mobilization to accelerate the ethical development and eventual global delivery of AIDS vaccines and other new HIV prevention options as part of a comprehensive response to the pandemic.

PxWire January-March 2011, Vol. 4, No. 1

PxWire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research, implementation and advocacy. This issue of PxWire takes inventory of the regulatory, trial-planning and scientific agenda-setting steps that are being taken with respect to recent positive trial results. It reviews ongoing and proposed next steps that have been triggered by the Thai prime-boost AIDS vaccine trial, the CAPRISA 004 microbicide trial and the iPrEx trial of once-daily TDF/FTC for pre-exposure prophylaxis.

2010 AVAC Report: Turning the Page (Thai translation)

The AVAC 2010 Report, Turning the Page, highlights that the biomedical prevention field is entering the next chapter of its development. The past year brought the first evidence, from the Thai Prime-Boost trial, that an AIDS vaccine could prevent HIV in humans, as well as significant preclinical findings around potent, HIV-specific neutralizing antibodies.

At the same time, two microbicide trials testing the candidate PRO 2000 yielded seemingly different, but ultimately disappointing results, and the field now prepares for the release of results from CAPRISA 004, the first ARV-based microbicide effectiveness trial.

Press Release

Evidence that daily antiretroviral pill reduces HIV risk in gay men is a major breakthrough says AVAC: Public health agencies and communities must move quickly to translate trial results into impact

New York, 23 November 2010 – “This is a great day in the fight against AIDS. The positive results of the iPrEx oral PrEP study are a major milestone in HIV prevention research and provide important information about how antiretroviral drugs might be used for prevention by HIV-negative people at high risk for HIV infection,” said AVAC Executive Director Mitchell Warren.

“It’s a result that requires immediate action. Because the pill evaluated in iPrEx is licensed and available as treatment for HIV-positive people, gay men and others at risk of HIV need immediate information about what these data tell us and what questions remain. Moreover, gay men and others at risk of HIV need to give crucial input and have influence on what the next steps for this new intervention might be,” Warren said.

“There is a global imperative to act on the results with ambitious, carefully prioritized research and implementation agendas, including strategic demonstration projects,” Warren continued.

The iPrEx pre-exposure prophylaxis, or PrEP, trial evaluated the safety and effectiveness of a once-daily dose of the antiretroviral drug TDF/FTC (brand name Truvada) for HIV prevention among 2,499 HIV-negative gay men and transgender women who have sex with men. At the end of the three-year trial, there were 36 infections in participants who received TDF/FTC and 64 in placebo recipients. This translates into an average 43.8% reduction in HIV risk overall in participants who received TDF/FTC compared to those who received the placebo.

“We congratulate the trial sponsors, scientific collaborators and partners who conducted this landmark global trial. We especially want to thank the nearly 2,500 gay men and transgender women from four continents whose altruism and commitment as trial volunteers made this effort possible,” Warren added. “The commitment of the iPrEx volunteers is especially important in light of the current human rights struggles in many countries and communities of gay men and other men who have sex with men. These volunteers and their communities have made an inestimable contribution to HIV prevention research and to the eventual development of new ways for both men and women to protect themselves from HIV. The world owes them and their communities an enormous debt of gratitude.”

“The identification of any new HIV prevention strategy is a landmark moment for the global AIDS response. iPrEx tells us that we have a new tool for gay men and transgender women. At the same time, the adherence and resistance data reported in today’s New England Journal of Medicine article tell us that there’s a lot of work to be done on identifying the best possible ways to deliver PrEP to these communities in ways that are safe, effective and grounded in a rights-based response. It’s also important to remember that even more data will emerge as follow up and analysis continue over the coming months,” Warren said.

One important source of additional information will be a follow-up trial, which will begin in early 2011 and be open to all participants from the original iPrEx trial. All HIV-negative participants who choose to join this open-label trial will receive the active TDF/FTC pill along with an HIV prevention package and will be counseled on daily use of the drug. However, monitoring and HIV testing will be less frequent, with the goal of learning about PrEP safety and effectiveness in a “real world” context.

“As this information is gathered, public health officials, regulatory bodies and policy makers must quickly provide clear statements on what we know and what we don’t, stressing that PrEP reduced risk in gay men and transgender women in the context of intensive counseling around safer sex, condom use and daily pill-taking, as well as regular monitoring including HIV testing.” Warren said.

The trial underscores the importance of providing a comprehensive prevention package. All of the iPrEx participants received a full prevention package, including condoms, safer sex counseling and treatment of sexually transmitted infections. At each monthly clinic visit, participants were tested for HIV and counseled about daily use of the trial drug, a level of counseling and testing not easily achieved outside of a clinical trial.

The trial also demonstrates that PrEP is only safe in people with confirmed HIV-negative diagnoses. Two cases of drug resistance documented in iPrEx occurred among two men who started PrEP while in the earliest phases of HIV infection, and therefore did not test positive for HIV using the trial’s diagnostics.

iPrEx shows that adherence to the drug regimen is essential. Participants who received TDF/FTC and had detectable levels of drug in their blood were at much lower risk of HIV compared to participants who received TDF/FTC and had no drug in their blood. The trial also analyzed risk of infection as it related to reported rates of pill taking. Participants who reported taking their pills correctly and consistently the majority of the time had significantly lower risk of HIV infection compared to those who reported taking the pills less frequently.

These data can’t be extrapolated to people at risk of HIV via heterosexual sex or injection drug use. Differences in biology of the vagina and rectum, and between HIV risk in sexual versus injection exposure make it essential that ongoing trials looking at PrEP in these contexts must continue.

“iPrEx is the first of several PrEP trials to provide results. There are more than 20,000 participants enrolled in additional PrEP trials worldwide that must continue,” said Warren.

The iPrEx findings add to a growing body of evidence confirming the powerful potential of antiretroviral drugs for HIV prevention. This includes findings from CAPRISA 004, a trial of 1% tenofovir gel as an HIV prevention tool for heterosexual women, which found that women who received the gel had an estimated 39 percent lower risk of infection compared to those who received an inactive placebo gel.

After many years of disappointing results from biomedical prevention trials, iPrEx and CAPRISA 004—along with the RV144 AIDS vaccine trial—mark the beginning of a new era of HIV prevention.

“New strategies come with new costs. We must ensure that any new strategy is well-validated before it is widely introduced, and that this introduction comes with new resources and not at the expense of any proven prevention modality,” said Warren.

“As we move towards potential PrEP implementation, it is critical to remember that millions of HIV-positive people around the world, including thousands in the United States, lack access to the HIV treatment they need, which is often the same drug used in this trial,” Warren said. “We can and must find a way to ensure that PrEP is a part of comprehensive, well-funded response to HIV. That means ensuring access for all who need it to existing HIV prevention and treatment options; ensuring continued research to find and refine effective new options, including PrEP, microbicides, vaccines and the possibility of treatment as prevention; and planning for integrating these new interventions into combination programs.”

Additional information about the trial is available on the official iPrEx trial website at www.iprexnews.com.

More information about key issues around the iPrEx study and the future of PrEP generally is available in AVAC’s PrEP and the iPrEx Trial FAQ that is online at www.avac.org/iprex.

Contact:  Mitchell Warren, +1-914-661-1536, ###

Press Release

Preliminary Safety and Adherence Data from Oral PrEP Trial Released; Trial Not Designed to Evaluate Effectiveness

New York, NY – Preliminary data were presented today at the International AIDS Conference by the US Centers for Disease Control and Prevention (CDC) from a safety and acceptability trial of daily use of oral tenofovir in HIV-negative gay men and other men who have sex with men (MSM) in the United States. These data, which do not include any evaluation of PrEP effectiveness, add to the body of information about ARV-based prevention available to researchers, policy makers, community and other stakeholders.

This trial, known as CDC 4323, is one of several trials around the world testing the use of antiretroviral drugs to prevent HIV infection, a concept known as PrEP, or pre-exposure prophylaxis.

The findings presented today showed that no serious safety concerns emerged in the initial analyses. CDC also shared early findings about risk-taking among men in the study. The trial was designed so that some men began taking the daily oral tenofovir or a placebo pill immediately, while other participants were delayed by nine months. This design allowed the research team to gather information on how pill-taking affected sexual behavior in participants who were all receiving the same standard prevention package, including counseling about safe sex, condoms and STD testing for the duration of the trial. The preliminary analyses indicate that rates of risk behaviors were comparable between the participants randomized to begin taking tenofovir or placebo pills daily immediately compared to those who began after nine months of trial participation.

Importantly, these results did not provide any information on whether PrEP reduces the risk HIV infection. This trial focused solely on safety and behavior issues and was not designed to explore possible effectiveness of PrEP. Several studies that are studying possible PrEP effectiveness are currently underway.

“The information from this trial provides important pieces of information about the possible use of PrEP if it is proven effective in other ongoing effectiveness trials around the world,” said Mitchell Warren, AVAC executive director. “It is encouraging to hear there were no serious safety concerns and that the men in the study did not appear to increase risk-taking behaviors while taking a pill.”

“But much more safety, adherence and risk data will be needed before PrEP can be implemented if it is proven effective. And, importantly, this trial does not tell us anything about whether or not PrEP will work to reduce the risk of infection,” Warren added.

“Antiretroviral-based prevention research shows great promises, especially in the light of the positive results from the CAPRISA 004 microbicide proof-of-concept study released earlier this week. Although the CDC safety study used oral tenofovir, the same antiretroviral that was formulated as a gel in the CAPRISA 004 microbicide study, it is important not to extrapolate between the two studies. There are a series of ongoing trials that still need to be completed before we know whether PrEP can be added to our list of available HIV prevention options. Each of these trials provides a piece of the puzzle of how antiretrovirals might be used by HIV-negative people to reduce their risk of acquiring HIV,” Warren said.

More information about PrEP research is available in AVAC’s publication A Cascade of Hope and Questions: Anticipating results of ARV-based HIV prevention trials, available at avac@avac.org.

Contacts:  Mitchell Warren, +1-914-661-1536, mitchell@avac.org 
Kay Marshall, +1-347-249-6375, kay@avac.org

Press Release

New Edition of Guidelines for Communities in HIV Prevention  Research Released at International AIDS Conference

GPP Plays Critical Role in Moving HIV Prevention Research Agenda Forward

VIENNA – The draft second edition of The Good Participatory Practice (GPP) Guidelines for Biomedical HIV Prevention Trials were released yesterday at the International AIDS Conference in Vienna by AVAC and UNAIDS. The GPP Guidelines aim to provide trial funders, sponsors, and implementers with systematic guidance on how to effectively work with a range of stakeholders as they design and conduct biomedical HIV prevention trials.

The guidelines were developed by AVAC and UNAIDS in consultation with a broad range of global stakeholders who have provided perspectives since the first edition was published in 2007. AVAC and UNAIDS are now seeking feedback on the draft second edition from those with interest and expertise in HIV prevention research until 31 October, after which the final second edition will be published.

Clinical trials are guided by Good Clinical Practice, Good Laboratory Practice, and other guidelines and regulations that cover scientific and general ethical conduct, but global guidelines had not existed for community engagement before the first publication of GPP.

“Recent breakthroughs, including positive results from the CAPRISA 004 microbicide trial, have reenergized prevention research, and around the world, thousands of research participants and hundreds of researchers and trial site staff are working together find new HIV prevention options. Thousands more will be needed as we work to find new solutions to ending the AIDS epidemic,” said Mitchell Warren, executive director of AVAC.

“The GPP Guidelines were developed to fill an important gap in the conduct of biomedical HIV prevention research and to help research teams, trial sponsors, trial funders, communities, advocates, and other stakeholders plan, implement, and evaluate community engagement in trials, reduce unnecessary conflict and ensure that research is meaningful to both communities and trial implementers,” Warren added.

“AVAC and UNAIDS is pleased to release this new version of the GPP guidelines at the conference at which the groundbreaking results of the CAPRISA tenofovir microbicide gel trial have been presented, recalling that it was the stopping of antiretroviral pre-exposure prophylaxis trials in 2004 that first inspired the development of the GPP guidelines,” said Dr. Catherine Hankins, UNAIDS’ chief scientific adviser.
The GPP guidelines include:

Guiding Principles of GPP that serve as the foundation of the relationship between trial funders, sponsors, implementers, and other stakeholders.
GPP Standards that trial funders, sponsors, and implementers should follow when designing, preparing for, conducting, and concluding a biomedical HIV prevention trial.

The GPP Guidelines are available online at: www.avac.org/gppdocuments or www.unaids.org.

AVAC Contact: Kay Marshall, +1-347-249-6375, kay@avac.org
UNAIDS Contact: Saya Oka, +41 22 791 1697, okas@unaids.org

Px Wire January-March 2010, Vol. 3, No. 1

PxWire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research, implementation and advocacy. Highlights in this issue of PxWire include updates on: the results from MDP 301, a trial of the microbicide PRO 2000, which lay to rest its prospect as a viable microbicide; CDC’s newly modified PrEP trial (TDF2 in Botswana), which changed its status as an efficacy trial to a safety and behavioral study; the evolving effort to understand the Thai prime-boost AIDS vaccine results; recent NIH grants that nearly double global spending on rectal microbicides; and a timeline of 2010 trial milestones—what trial results are expected and what new studies are scheduled to commence?

Press Release

Piecing Together the HIV Prevention Puzzle: AVAC Report Assesses Progress in AIDS Vaccine, Microbicide and PrEP Research and Calls for Urgent Coordination and Leadership in Advance of Upcoming Results

New York, NY — “It’s an exciting time in HIV prevention research. We will see results from a number of critically important HIV prevention research trials this year, as well as see the start of new trials around the world that will yield important answers in the years to come,” said Mitchell Warren, AVAC executive director, at the release of AVAC’s 13th annual report of the field.

“But scientific, community and political leaders must act now to plan for continued research and implementation of effective strategies, or this excitement will be wasted.”

The report — Piecing Together the HIV Prevention Puzzle — looks at AIDS vaccine research, where there is an energized focus on discovery, innovation and basic science and looks at the broader HIV prevention field, particularly the implications of pre-exposure prophylaxis (PrEP) and other strategies in efficacy trials today.

This analysis of the HIV prevention field comes in a year that has already brought disappointment as well as intriguing results from various prevention studies. At the same time, even trials that failed to show overall benefit, such as the Step Study of the Merck HIV vaccine candidate, have continued to generate new, valuable information and questions that would not otherwise exist.

These trials have succeeded as a result of increasingly robust partnerships between researchers and communities grappling with HIV, including gay men around the world and heterosexual women in Africa. These partnerships, along with the persistently high rates of new infections, are a continual reminder of the global commitment to and need for continuing the search for new prevention for as long as it takes.

“We hope to have new prevention intervention pieces to add to the puzzle in the next few years,” said Warren. “But as the slow implementation of male circumcision to reduce heterosexual men’s risk of HIV infection reminds us, we need extensive planning and guidance to ensure research results are translated into real impact against the epidemic. We can’t afford to wait for efficacy results before we begin to plan. We must anticipate and tackle the major hurdles for implementation now.”

The Report identifies major issues for implementation of new prevention options, including:
–   Ongoing global failures to scale up access to HIV testing and counseling services.
–   Persistent inattention to the needs of gay men and other men who have sex with men around the world.
–   Gaps in health care infrastructure that will complicate introduction of any new strategy.

In the Report, AVAC also underscores the importance of WHO and UNAIDS getting involved in planning for the results from PrEP trials before data are available.
“WHO and UNAIDS, along with other stakeholders, need to combine their strengths now to provide leadership and coordination so that the world is ready to work with results from the many ongoing PrEP trials,” said Warren.

Positive results from current vaccine, PrEP and microbicide trials will also present challenges and opportunities for other ongoing and planned HIV prevention trials.

“There has been concern that positive results from PrEP trials would require vaccine or microbicide trials to become larger, longer and more expensive, as PrEP could become a standard of prevention in these trials,” said Warren. “But we believe that success in one trial will open up possibilities and options for research that could combine AIDS vaccines and other interventions as they emerge.”

To help guide efforts in new areas of research and sustain ongoing research, AVAC calls for researchers and trial sponsors to begin planning on how combination strategies can be evaluated.

As the field looks to fit the puzzle pieces together, the AVAC Report also identifies a number of big questions in AIDS vaccine research for 2009 and beyond, focusing on issues such as cell-mediated viral control, HIV genetic diversity, the role of animal models, immune activation, antibodies and adjuvants.

In its analysis of the vaccine field, AVAC also assesses the progress and future potential of the Global HIV Vaccine Enterprise and considers the impact of results from the Thai prime-boost vaccine trial that are expected in September. With over 16,400 participants, this is the largest AIDS vaccine trial ever undertaken.

“In AIDS vaccine and HIV prevention research today, we see a fertile mix of big science and individual efforts, of product-oriented work and of slow and steady basic science,” Warren added.

“What we need now is a quick, strategic, scientific analysis of all the efforts underway, with a goal of identifying gaps and opportunities for synergy both within the AIDS vaccine field and across the vaccine, PrEP, and microbicide fields. AVAC is excited to help move the HIV prevention field toward a collaborative agenda and to prepare now for implementing potential new prevention options.”

Piecing Together the HIV Prevention Puzzle is available at http://www.avac.org/reports.htm.

# # #

Press Release

New AVAC Report on Pre-Exposure Prophylaxis Calls for Immediate Planning to Anticipate Study Results of Potential New HIV Prevention Option:

Mexico City, Mexico, August 3, 2008 — The AIDS Vaccine Advocacy Coalition (AVAC) today released a new report, Anticipating the Results of PrEP Trials, calling for increased action from governments, global health institutions, donors, researchers, and advocates to prepare for initial results — expected as early as 2009 — from the first trials of antiretroviral drugs being tested for HIV prevention, known as PrEP or pre-exposure prophylaxis. The report also provides the most up-to-date information about ongoing and planned PrEP research, and lays out an agenda for action on key issues that must be addressed as research on this promising HIV prevention intervention moves forward.

The new report is available online at http://www.avac.org/prep08.pdf.

PrEP clinical trials are currently planned or underway in countries in Africa, Asia, Latin America and North America. These studies are looking at the safety and efficacy of PrEP, an unproven strategy in which HIV negative people could take an antiretroviral drug (ARV), or combination of ARVs, on a regular basis in the hopes of reducing their risk of acquiring HIV.

The AVAC report was released today at a special session of researchers, advocates and other stakeholders, held at the XVII International Conference on AIDS in Mexico City to discuss the challenges of translating PrEP and other HIV prevention research into effective policy and practice.

“PrEP trials are taking place within a changing landscape of HIV prevention research,” said AVAC Executive Director Mitchell Warren. “Disappointing results have emerged from recent studies of vaccine and microbicide candidates, while male circumcision was found to be partially effective at preventing HIV transmission in some populations and is being rolled out in some African countries.

“Although still unproven human clinical research, PrEP is considered one of the promising clinical interventions against HIV currently in development,” Warren continued. “By mid-2009, more people will be enrolling in PrEP studies than in both HIV vaccine and microbicide efficacy trials combined. Advocates and communities affected by HIV need to understand PrEP and its implications for the AIDS advocacy and global health agendas, and government and private funders committed to global health must step forward now to ensure that PrEP research is fully funded.”

“We cannot wait for the study results to begin to prepare for the optimal use and delivery of PrEP,” said Pedro Goicochea, an investigator of the iPrEx PrEP study currently underway in Peru and Ecuador “Instead, we should look ahead to consider all of the possible outcomes of these trials and make real plans for making PrEP available to those who can benefit from it, as quickly and safely as possible if it is proven effective.”
Anticipating the Results of PrEP Trials provides an up-to-date status report on current PrEP research; addresses concerns about PrEP, including the possibilities of drug resistance, partial efficacy, and the potential for increased risk behavior and social stigma; looks at the potential impact of PrEP on future HIV prevention research; and considers what questions should we be preparing to ask now based on possible different research outcomes as PrEP studies begin reporting data in the next few years.

“This report provides an important overview of PrEP research and lays out the many difficult issues that are critical for advocates, communities and public health experts to understand as trials continue and report results,” said Warren. “We cannot shy away from discussing issues such as potential drug resistance, the difficulty of adhering to a once-a-day pill regimen for people who are not sick, or the cost of providing PrEP. This report and today’s meeting lay the groundwork for these important discussions.”

AVAC’s report identifies five priority issues that need attention now, including:
1. Ensure that current clinical trials have the best chance of providing results: Clinical trials now underway in Thailand, Africa, Latin American and the U.S. could establish the safety and effectiveness of PrEP, but only if these trials produce clear answers. Trial sponsors, regulatory agencies and the global health community must work together to ensure that these studies are supported to produce the data needed to determine next steps on the possible use of PrEP.

2. Identify and invest in additional research: A plan for launching additional studies — including studies on the safety and efficacy on intermittent PrEP dosing, bridging studies in additional populations, and safety and efficacy of other candidates — is needed now and will require additional funding.

3. Plan now for optimal use of PrEP: A plan of action for using PrEP to maximum public health impact should be developed now. This plan should address the issues set out in a Lancet paper of July 2007, which called for assessing appropriate settings and populations for PrEP use, determining what level of efficacy would warrant widespread delivery and determining where targeted vs. more generalized delivery would be more appropriate.

4. Prepare for global procurement and delivery of PrEP: Plans for PrEP delivery must include a well-planned and resourced campaign to deliver PrEP, an understanding of which global funders will pay for PrEP, plans for rollout, and guidance and support similar to that implemented for male circumcision.

5. Provide adequate financing: Underinvestment in PrEP is hampering progress and must be corrected. Government and private funders committed to global health must step forward now to ensure that PrEP research is fully funded.

AVAC’s Anticipating and Understanding Results series provides timely analysis of trials of new HIV prevention options. For other publications in the series, visit http://www.avac.org/.

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About AVAC: Founded in 1995, the AIDS Vaccine Advocacy Coalition (AVAC) is an international nonprofit, community- and consumer-based organization that uses public education, policy analysis, advocacy and community mobilization to accelerate the ethical development and global delivery of AIDS vaccines and other HIV
prevention options. For more information, visit http://www.avac.org/.

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