Close to 100 openly HIV-positive gay and bisexual men from across the United States and around the world have signed a new letter (http://tinyurl.com/pozPrEPletter) calling for an open discussion, “based on facts rather than on fear or misinformation,” of the challenges and opportunities presented by pre-exposure prophylaxis (PrEP) for HIV prevention in gay and bisexual men and transgender women. The new open letter is designed in part to urge FDA review of PrEP and to clarify facts about important PrEP research that advocates say have been misrepresented in a paid ad campaign sponsored by the AIDS Healthcare Foundation (AHF).

Pre-exposure prophylaxis, or PrEP, is a new HIV prevention method in which an uninfected person takes a daily HIV medication to reduce HIV infection risk. Data from an international study released in November, 2010 called iPrEx found that men and transgender women who have sex with men who received a daily single-tablet dose of the HIV drugs tenofovir and emtricitabine along with condoms and safe sex counseling had an average of 42% fewer HIV infections than those who received condoms and counseling alone. Much higher rates of protection were achieved among participants who took PrEP consistently.

Most of the HIV prevention community welcomed the news of a new tool that could significantly reduce infections in the populations at highest risk for HIV in many parts of the world. One HIV treatment provider, however, the AIDS Healthcare Foundation, has taken out an extensive series of full-page advertisements in gay papers around the country claiming that gay and bisexual men will act recklessly and will spread HIV if they are allowed to use PrEP. The AHF ad campaign claims that it is supporting gay and bisexual health by urging the U.S. FDA to ignore the PrEP study.

Today’s open letter challenges both the tone and content of the AHF communications and encourages “a full and factual discussion of the pros and cons of PrEP… based on facts, not misinformation.” Reminding the world that “gay and bisexual men invented safer sex…and have worked tirelessly to prevent new HIV infections,” the letter also points out that gay and bisexual men account for more than half of new HIV infections in the United States and are in particular need of new HIV prevention approaches.

“As an HIV positive gay man I signed this letter because I learned from experience we need all credible options to stop this epidemic. I owe my life to the fact that advocates and activists have pushed hard for decades to make effective AIDS drugs available to HIV-positive people,” said Kali Lindsey. “Now we know that AIDS drugs can also play an important role in the health and well-being of HIV-negative gay men, how could we not move forward to reap the benefits of this research. It is not an option to ignore these findings.”

In July of this year the results of two addition studies, Partners PrEP (led by the University of Washington Department of Global Health) and TDF2 (led by the U.S. Centers for Disease Control and Prevention) demonstrated that PrEP is also safe and effective in heterosexual women and men. The Partners study found that participants who received PrEP experienced an average of 62-73% fewer HIV infections than those who received placebo. The TDF2 trial, conducted by the U.S. Centers for Disease Control found that the risk of HIV infection dropped by an average of 63% among those who received PrEP in addition to condoms and counseling. Data expected from the FEM-PrEP trial, which was stopped in April 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.

The new letter acknowledges that the PrEP, “is no magic solution to the HIV crisis,” and that research, “raises important questions…includ(ing) how to best support regular PrEP use; how to ensure the continued use of condoms and other precautions for those who decide to take PrEP; how to target PrEP to those who will benefit most; and how to pay for this new HIV prevention tool.” Its signers express their commitment “to promoting safer sex and the open exchange of accurate information on HIV prevention,” and to “clarify the facts about PrEP, open up community discussion and make clear our belief that we are entitled to respect, accurate information and new HIV prevention tools.” The letter concludes by calling on all interested parties to “get the facts about PrEP, seek information, and express opinions…but to do so based on real information, not fear of the scientific process or prejudice against gay/bi men.”

The letter was coordinated by a group of U.S.-based AIDS advocacy organizations, including AIDS Foundation of Chicago, AVAC, International Rectal Microbicide Advocates (IRMA), and Project Inform.

A copy of the sign-on letter supporting an informed debate on PrEP for gay and bisexual men is below. Openly HIV-positive gay and bisexual men who wish to add their name to the letter can do so at: http://tinyurl.com/pozPrEPletter.

Contact:
Kay Marshall (AVAC), [email protected], +1-347-249-6375

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, [email protected], +1-914-661-1536
Kay Marshall, [email protected], +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.

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, ###