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, Nov. 23, 2010 /PRNewswire-USNewswire/ -- "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.

What PrEP is and What PrEP is not

• In iPrEx, daily TDF/FTC helped prevent HIV among HIV-negative gay and bisexual men when used with condoms and other HIV prevention methods. The observed benefit was seen among participants who also received monthly HIV testing, counseling, condoms, treatment for sexually transmitted infections and other services.
• iPrEx evaluated one particular HIV drug as PrEP. This pill contains a combination of two drugs, TDF/FTC. Other HIV drugs are being considered for oral PrEP, but there are no data on other oral agents.
• PrEP is not yet recommended for use. iPrEx tested TDF/FTC for PrEP under specific research conditions. More information is needed to translate the trial finding into "real world" programs for gay men. iPrEx demonstrates that individuals taking TDF/FTC for prevention must have a confirmed HIV negative diagnosis and see a doctor regularly. This study showed that PrEP using TDF/FTC is safe and effective in gay men who were instructed to take the drug daily, received monthly HIV testing and ongoing monitoring for side effects and who received comprehensive HIV prevention services. There are risks, including possible HIV drug resistance and side effects. The only way to minimize these risks is through ongoing monitoring and testing.
• You can still get HIV when taking PrEP. iPrEx found that PrEP using TDF/FTC is only partially effective. If approved for use as an HIV prevention strategy, it should be used with – not instead of – condoms, safer sex practices and other HIV prevention methods.
• PrEP is not a "vaccine" or a "morning-after" pill. The strategy as studied involves ongoing pill-taking. In iPrEx, TDF/FTC was effective when participants received intensive counseling to take the drug every day. There is no evidence supporting the effectiveness of this PrEP drug in any other context. In the trial, participants who reported taking the TDF/FTC pill consistently had the highest levels of protection.
• PrEP is not for everyone at risk of HIV. The iPrEx trial showed that the TDF/FTC pill was partially effective for some gay and bisexual men at high risk of HIV, who took the pill regularly, were counseled to reduce HIV risk behavior and were closely monitored. The iPrEx results cannot be extrapolated to other populations. Only other PrEP studies underway among heterosexual men and women and injecting drug users will tell us whether this or other PrEP strategies work in these other groups.

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.

SOURCE AVAC