New York, NY AVAC hails the recommendation by an FDA Advisory Committee that emtricitabine/tenofovir disoproxil fumarate (TDF/FTC or Truvada) be approved for use as pre-exposure prophylaxis (PrEP) among sexually active adult men and women. Citing the urgent need for new HIV prevention options to stem HIV infections, AVAC urges the FDA to issue an approval for all men and women at risk, and is calling on public health agencies, governments, advocates and funders to take action to ensure access to TDF/FTC as PrEP.

“This brings us closer to a watershed for global HIV prevention efforts,” said Mitchell Warren, executive director of AVAC. “PrEP, while not a panacea, will be an essential additional part to the world’s success in ending AIDS. For the millions of men and women who remain at risk for HIV worldwide, each new HIV prevention option offers additional hope that we will achieve the end of the epidemic.”

“The evidence from the clinical trials presented today is clear:  If you perceive yourself to be at risk, if you take your pill daily, and if you receive the drug as part of a comprehensive package of HIV prevention interventions and testing, oral PrEP can dramatically reduce your chances of becoming infected,” Warren said.

Noting that the FDA typically, but not always, follows its committees’ recommendations, Warren said, “With their support for approval, the FDA’s expert panel and its own scientists have followed the evidence.  We hope and expect that the agency will follow their sound advice.”

“As a young black gay HIV-negative man, I see that the current prevention options are not stemming HIV incidence in my community,” said Matthew Rose, policy chair of the Young Black Gay men’s Leadership Initiative and an AVAC PxROAR partner. “I know that a single drug or prevention strategy will not end this epidemic. But PrEP will give young gay black men tools that will allow them to manage their situation and make their own HIV prevention choices based on knowing all the options that exist.”

An action agenda for PrEP implementation
In anticipation of an FDA approval for TDF/FTC as PrEP, AVAC is calling for immediate actions to ensure that PrEP can be made available to people at risk of HIV quickly, safely and through programs that maximize safety, use of comprehensive HIV prevention and impact on HIV infections. These actions should take place in the US and in other countries that may take the FDA ruling as a positive signal for national introduction of TDF/FTC as PrEP.

“After decades of research, it’s thrilling that we can begin talking about access to a powerful new HIV prevention option,” Warren said. “Some funders and policymakers have been awaiting a signal from the FDA before launching demonstration projects or developing implementation plans.  The time for waiting is over. We need to get on with the work of setting priorities and rolling out PrEP to people who can benefit the most.”

AVAC’s recommendations include:

• Public health guidance:  The US Centers for Disease Control and Prevention, the World Health Organization and other public health agencies should issue guidance on the appropriate use of daily TDF/FTC as PrEP in different populations and settings as soon as possible. Guidance is needed by providers and people at risk, and to help governments and funders set priorities for PrEP implementation.
• Demonstration projects:  Real-world studies are urgently needed to answer important questions about how best to implement PrEP, including who can benefit most; how to provide PrEP safely and efficiently; how to integrate PrEP with other essential prevention methods such as condoms; and how to ensure high levels of adherence, which research has shown to be essential for PrEP to work. Currently, only a limited number of demonstration projects are planned or underway.
• Funding:  In addition to funding robust demonstration projects, donors and governments should be planning for significant investments in well-designed PrEP initiatives. Funding for PrEP should not detract from other essential HIV prevention and treatment efforts. However, funders should explore ways to repurpose funds that currently support lower-impact activities.
• Additional research:  Studies are currently underway to test PrEP in additional populations, including injecting drug users and to evaluate new drugs and less frequent PrEP dosing schedules. Trial sponsors, manufactures and the FDA should stand ready to act on new data and further expand options for preventing HIV infection.

“PrEP, together with other prevention strategies that we have now and those still to be developed, could help to significantly reduce the global burden of HIV infections and could be a life-saving intervention for some men and women, Warren added. “Multiple clinical trials have clearly shown that PrEP is safe and effective when used as prescribed. We all must now act on the scientific evidence and translate it into practice and impact. We simply cannot afford to dismiss any new options in the quest to end AIDS.”

For a PDF version of this press release, click here.

Contact:
Mitchell Warren, [email protected], +1-914-661-1536
Kay Marshall, [email protected], +1-347-249-6375

New York, NY — In public comments submitted this week, a group of 14 leading HIV/AIDS and health organizations stated their support for Food and Drug Administration (FDA) approval of emtricitabine/ tenofovir disoproxil fumarate (TDF/FTC or Truvada) as pre-exposure prophylaxis (PrEP) to prevent HIV infection in adult men and women. Their comments, submitted in advance of a May 10 FDA Advisory Committee meeting, pointed to compelling evidence on the efficacy of TDF/FTC as PrEP and highlighted the unique potential of this intervention to help slow the HIV epidemic in the US.

With PrEP, HIV-negative individuals who are at risk for HIV take anti-HIV medications in order to reduce their chances of becoming infected if exposed to the virus. At the May 10 hearing, the FDA will consider data from clinical trials showing that TDF/FTC reduced the risk of sexual transmission of HIV in populations including men who have sex with men (MSM) and heterosexual women and men.

“The US and international AIDS community overwhelmingly supports FDA’s priority review of this potentially game-changing new tool to prevent HIV,” said Mitchell Warren, executive director of AVAC. “The evidence is increasingly clear that daily PrEP can help reduce HIV risk in women and men who take it consistently as prescribed. While no single tool will be enough to stop the spread of HIV, PrEP could be a vital part of a comprehensive, global strategy to end the AIDS epidemic.”

Despite some progress in reducing HIV incidence using other available methods, approximately 50,000 people become newly infected with HIV every year in the United States, and 2.6 million people were newly infected with HIV worldwide in 2010. Globally, half of all people infected with HIV are women and girls. In the United States, HIV infection continues to take a disproportionate toll on African Americans and Latinos; MSM, including transgender individuals; and the poor. Driving down HIV infection rates is a primary objective of the U.S. National HIV/AIDS Strategy, and is at the core of global efforts to end the AIDS epidemic.

“Today’s HIV prevention tools, including condoms, remain as essential as ever, but it’s clear that they aren’t enough,” said Deborah Cohan of the Bay Area Perinatal AIDS Center. “If approved, PrEP would help address important gaps, including the need for women to have more ways to protect themselves without having to rely on their male partners.”

“Evaluation of new prevention tools is critical to reducing the devastating impact of HIV among Black Americans,” said Douglas Brooks, MSW, Senior Vice President of the Justice Resource Institute. “No single approach will be right for everyone, but PrEP could offer a much needed option for some. The benefits could be especially great for Black gay or bisexual men, who account for nearly one-quarter of new HIV infections in our nation today.”

Modeling studies have shown that widespread access to PrEP could reduce new HIV infections, and thus the scale of the global HIV epidemic, substantially around the world. The FDA’s decision on TDF/FTC as PrEP could help pave the way for global health funders and developing countries to step up their planning for implementation.

Evidence for PrEP: What the Science Tells Us
At the May hearing, an FDA Advisory Committee will consider data from a wide range of safety and efficacy studies, including two pivotal clinical trials of TDF/FTC as PrEP:

• The Partners PrEP trial, which found that daily TDF/FTC reduced HIV infections by 73 percent among heterosexual couples in Africa in which one partner was HIV infected and the other was not. Efficacy was 90 percent among those who adhered closely to their daily drug regimen.
• An international study called iPrEx found that daily use of the drugs reduced HIV infections by 42 percent among MSM, and by more than 90 percent among participants who took their medication consistently enough for the drug to be detected in their blood.

These studies demonstrate that PrEP was safe, with minimal side effects and no significant risk of drug resistance. These and other trials also indicate that effectiveness of TDF/FTC as PrEP depends greatly on individuals’ adherence to the PrEP regimen. In each trial, when adherence was low, there was low or no protection, pointing to the central importance of strategies to maximize adherence.

“If FDA approves PrEP, we’ll still have a lot of work to do, just as with any other new drug. We’ll have many questions to answer in order to use PrEP effectively to reduce HIV infections,” said David Munar, President and CEO of the AIDS Foundation of Chicago. “The essential next step will be to launch additional demonstration projects in a wide range of populations and settings. These real-world projects will help us understand how to achieve higher levels of adherence, how to best combine PrEP with other approaches, and which specific populations can benefit the most. While a handful of these real-world studies are now being planned, we need to pick up the pace.”

Summary of the Joint Comments to FDA
Based on the clinical trial results to date, the groups indicated their support for FDA approval of TDF/FTC among both men and women. They also highlighted evidence demonstrating the safety of TDF/FTC when used as PrEP, while urging the FDA to ensure appropriate labeling and post-marketing surveillance to ensure that any future safety concerns will be quickly identified and addressed. In addition, the groups also called for the full participation of communities most likely to benefit from PrEP in any future discussions about FDA-required educational/informational materials and programs to support safe use of TDF/FTC as PrEP.

The full text of the comments is available here. The comments were signed by the following organizations:

• AIDS Foundation of Chicago
• AIDS United
• AVAC: Global Advocacy for HIV Prevention
• Bay Area Perinatal AIDS Center
• Black AIDS Institute
• The Fenway Institute
• International Rectal Microbicide Advocates
• Justice Resource Institute
• National Black Gay Men’s Advocacy Coalition (NBGMAC)
• National Minority AIDS Council (NMAC)
• Project Inform
• San Francisco AIDS Foundation
• SHERO Empowerment Network
• SisterLove

Contact:
Mitchell Warren, [email protected], +1-914-661-1536
Kay Marshall, [email protected], +1-347-249-6375

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New York, NY — AVAC strongly supports the California HIV/AIDS Research Program (CHRP) in launching new studies to evaluate the “real-world” use of oral pre-exposure prophylaxis (PrEP), a promising HIV prevention strategy recently shown to be effective in clinical trials.

The three CHRP-funded demonstration projects will provide vital information on how to implement recent research results to reduce HIV infections through the use of PrEP among HIV-negative people at high risk. Importantly, these studies will explore PrEP in the context of other new strategies to engage and retain HIV-infected individuals in care and treatment.

“PrEP, together with other prevention strategies, could help to significantly reduce HIV infections worldwide and could be a life-saving intervention for some men and women,” said Mitchell Warren, AVAC executive director. “Multiple clinical trials have clearly shown that PrEP is effective when used as prescribed. We now have an obligation to figure out how best to roll it out in the real world for people who need it and are able to use it, without delay.”

PrEP involves the use of daily anti-HIV medications by people who are uninfected but at high risk for HIV. Randomized-controlled trials that were closely overseen by independent ethical and regulatory bodies have shown that daily PrEP with a combination of the drugs tenofovir and emtricitabine (TDF/FTC, or Truvada) can reduce the risk of infection among gay men and other men who have sex with men (MSM), transgender women and heterosexual men and women. While other trials have shown no effect, the overall message is clear: adherence to the PrEP regimen is essential. Among trial participants who consistently took the PrEP pill, the risk of infection was reduced by more than 70 percent, while little or no benefit was seen when participants did not take the pill as prescribed.

“Finding ways to ensure that people who can benefit from PrEP are supported in taking the medication consistently has to be a top priority,” said Warren. “Real-world demonstration projects are the only way to test different approaches and find out what works. A year and a half after the first positive PrEP results, almost none are under way. This kind of delay is of severe concern to anyone interested in expanding the options for preventing HIV in some of the hardest-hit populations here in the US and worldwide.”

In addition to addressing adherence, demonstration projects are needed to answer questions about which populations benefit the most from PrEP and how to deliver it to them safely, effectively and at reasonable cost. They can also help determine the most effective ways to integrate PrEP with existing prevention strategies, such as male and female condoms, which remain essential to reducing HIV infections. AVAC and other advocates have called on governments and AIDS funders to launch an array of PrEP demonstration projects around the world, including the full range of populations that may benefit from the intervention.

“The California studies are smart to focus on gay men and transgender women, who are by far the most affected by HIV in the U.S. Now we need to do the same for other populations, especially the millions of women around the world who remain at risk. PrEP could help address the urgent need for new HIV prevention methods that women can control,” said Warren.

Warren also pointed to the upcoming U.S. Food and Drug Administration review of TDF/FTC as PrEP, saying, “The FDA’s review is a critical step in establishing access to PrEP and ensuring that accurate information is available to providers and potential users.” AVAC expects to be among a number of advocates submitting oral and written comments at a May 10 FDA Advisory Committee hearing.

“Ethics demand that we do everything we can to make proven HIV prevention options available to those who need them, when they need them. AIDS activists have a history of pushing researchers and regulators to make treatment available to people living with HIV as quickly as possible. People at risk of becoming infected deserve no less,” Warren said.

Contact:
Mitchell Warren, [email protected], +1-914-661-1536
Kay Marshall, [email protected], +1-347-249-6375

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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.

New York, NY — An important step to expanding effective HIV prevention strategies has been taken by Gilead Sciences, Inc., says AVAC. Today, Gilead Sciences announced that it has submitted a dossier of research data to the US Food and Drug Administration (FDA) related to the use of the antiretroviral treatment drug TDF/FTC (tenofovir/emtricitabine, brand name Truvada) as a pre-exposure prophylaxis (PrEP) HIV prevention strategy.

PrEP for HIV prevention refers to the use of antiretroviral medications by HIV-negative people to prevent HIV infection. TDF/FTC, or Truvada, is currently used as part of highly effective combination antiretroviral treatment for HIV-positive people. Gilead announced that it was seeking FDA approval for a label change indicating that Truvada can reduce the risk of HIV infection in HIV-negative adults.

“The FDA should place Truvada for PrEP on its accelerated, priority review track. A determination from this regulatory agency on new labeling and other conditions of use would catalyze and clarify decision-making in the US and potentially internationally about where and how to use TDF/FTC as an HIV prevention strategy,” said Mitchell Warren, AVAC executive director. “Approval is not guaranteed as a result of today’s filing. AVAC looks forward to participating in the process that will allow responsible input to any review that promotes safe use to those who may potentially benefit from PrEP. It will also be critical to insure continued and unfettered access to TDF/FTC for HIV-positive people as part of life-saving treatment.”

Every year more than 50,000 people are newly infected with HIV in the United States and rates of infection have remained steady for many years, underscoring the need for new HIV prevention options for gay men and others at high risk of HIV infection in the US. Globally, rates of HIV infection have declined but remain unacceptably high, with women at particularly high risk. More than 2.7 million people were infected with HIV in 2010.

Two major international efficacy trials have found that TDF/FTC is safe and reduces risk of HIV infection among HIV-negative people. The iPrEx study among gay and bisexual men and transgender women, and the Partners PrEP study among stable heterosexual couples in which one partner is HIV-positive and one HIV-negative. In addition, TDF2, a smaller trial, provided additional information about the drug in young heterosexual men and women.

The FEM-PrEP trial among heterosexual African women at high risk of HIV infection recently determined that participants counseled to use oral daily TDF/FTC did not have any reduction in HIV risk compared to those participants counseled to use daily placebo. Additional data from this trial are expected in early 2012. The multi-arm VOICE trial, which is also looking at oral TDF/FTC among African women, is scheduled to report results in 2013. The VOICE trial recently announced that the trial arms testing oral TDF alone and 1% tenofovir gel did not provide any protection. (All participants in all PrEP trials were counseled about and provided with a comprehensive package of proven prevention tools.)

“Even though there have been mixed results on PrEP using TDF/FTC from various clinical trials, both the iPrEx and Partners PrEP data are strong and suggest that, in some contexts, a daily oral pill is a powerful prevention tool that individuals can use to reduce their HIV risk,” Warren said. “More analysis of the full range of trials will tell us why this strategy works in some populations, and not in others, but the need for new options in key groups—including gay men and women in stable partnerships—is so great that proceeding with the FDA review process is an appropriate and important next step.”

Participants in both the iPrEx and Partners trials are continuing to receive TDF/FTC in “open-label” periods of those trials, in which all participants are offered the drug that has been shown to be effective in reducing HIV risk. These open-label studies will generate information on patterns of adherence, impact on HIV risk and other variables outside of a highly controlled clinical trial environment. Visit www.avac.org/prep for more information about ongoing and completed PrEP studies.

“We know that PrEP is not a magic bullet and will not be the right intervention for everyone at risk of HIV infection, but it could be an important prevention option for many people who are unable to use other proven prevention options. An FDA-approved label indication and reasonable conditions of use would make it easier for providers and their clients to consider PrEP as a safe and effective prevention option, and pave the way for appropriate access in the United States,” Warren said. “We also know that TDF/FTC is an important part of treatment regimens for people living with HIV worldwide, and that decisions about when and how to use PrEP based on TDF/FTC can only happen in the context of uncompromised treatment access for people living with HIV.”

“We look forward to the rigorous FDA review process, which will include opportunities for public comment and debate about how Truvada as PrEP might be used,” Warren said. “At the same time, we must continue to rapidly expand testing, treatment and voluntary medical male circumcision, amongst the array of evidence-based interventions, while also accelerating research and development of additional new options, notably a range of ARV- and non-ARV-based prevention methods and vaccines to protect against HIV,” Warren added.

A PDF version of this press release is available here.

Contact:
Mitchell Warren, [email protected], +1-914-661-1536
Kay Marshall, [email protected], +1-347-249-6375

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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.

New York, NY — The announcement today that the 1% tenofovir gel arm of a large-scale HIV prevention trial known as VOICE will stop early is disappointing but is not the end of the road for tenofovir gel or antiretroviral (ARV)-based microbicides.

“This is a blow to the HIV prevention field but is not the definitive answer about whether 1% tenofovir gel is an effective HIV prevention product for women,” said Mitchell Warren, AVAC Executive Director. “New interventions are studied in multiple effectiveness trials for exactly this reason. CAPRISA 004, the first trial of 1% tenofovir gel, found effectiveness in women. VOICE found no effect. The FACTS 001 safety and effectiveness trial of tenofovir gel, which has just begun in South Africa and uses a different dosing strategy from VOICE, will provide additional information and hopefully clarity about the effectiveness of tenofovir gel.”

“One immediate priority is ensuring that communities directly connected to planned and ongoing trials of tenofovir gel are informed and engaged with discussions about the way forward. Finding prevention options that work for women must remain a top priority, and there is still crucial investigation of tenofovir gel as both a rectal and a vaginal microbicide, which must continue,” Warren said.

After a recent, scheduled interim review of trial data, the independent Data Safety and Monitoring Board (DSMB) for VOICE—a five-arm proof-of-concept trial that has enrolled more than 5,000 women in South Africa, Uganda and Zimbabwe—recommended that the 1% tenofovir gel arm of the study be stopped and that the women in that arm exit the trial in a structured process. The DSMB concluded that there was no possibility that daily use of tenofovir gel would show efficacy in preventing HIV in the context of the VOICE trial. Importantly, the DSMB found no safety issues in any arm of the trial. No other data from the trial have been released at this time.

In September, the VOICE trial DSMB met and recommended stopping the oral tenofovir (TDF, brand-name Viread) arm of the trial after it was determined that oral TDF could not be shown effective in the context of this trial.

VOICE will continue to evaluate oral TDF/FTC (a combination of TDF and emtricitabine (FTC), brand-name Truvada) with final results expected in late 2012.

In July 2010, results from the CAPRISA 004 trial showed that 1% tenofovir gel reduced the risk of HIV infection by 39 percent overall among the women in that trial. At this time, it is impossible to know why the results of VOICE and CAPRISA 004 were different. The differences could be related to the dosing schedule—women in CAPRISA 004 were counseled to use the gel before and after sex, while women in VOICE were counseled to use it daily—or it could be related to how frequently women used the gel or other variables. VOICE launched in 2009 with a five-arm trial design to evaluate the safety and effectiveness of oral TDF, oral TDF/FTC and 1% tenofovir gel, each used daily, compared to a placebo gel or placebo pill.

“Based on the limited information available at this time, we simply don’t know whether the lack of effect was due to biology, adherence, both, or something else. This is one reason why the ongoing FACTS 001 trial, which is evaluating a different dosing strategy, with different adherence requirements, should continue,” Warren said. “The concept of ARV-based prevention has been proven, but to meet the prevention needs of different populations we need the right drug at the right time in the right place. We hope that further research with tenofovir- and other ARV-based options will provide a range of new prevention options.”

The FACTS 001 trial of 1% tenofovir gel, which began enrolling in October and will include 2,200 HIV-negative women in South Africa counseled to follow the same dosing schedule as CAPRISA 004, should provide more information about how and if tenofovir gel might reduce risk of HIV infection in women. Results from FACTS 001 are expected in 2014. In addition, follow-on studies among women who participated in the CAPRISA 004 study will provide more critical information about the effectiveness and acceptability of tenofovir gel under different circumstances.

“We commend the VOICE trial team, the members of the DSMB and especially the more than 5,000 women who are participating in the trial,” said Warren. “VOICE has and will continue to provide critical information about both tenofovir-based PrEP and microbicides that will help move the HIV prevention research agenda forward,” Warren said.

The disappointing news from the VOICE trial is the latest development in a complex picture of what ARV-based prevention means for HIV-negative women. The Partners PrEP trial provided evidence of benefit that both daily oral TDF/FTC or daily oral TDF reduced HIV-negative women’s risk of acquiring HIV from an HIV-positive male spouse or stable partner. (The same benefit was observed for HIV-negative men with HIV-positive female partners.) The trial enrolled serodiscordant couples, in which one partner was HIV- negative and one was HIV-positive. The smaller TDF2 expanded safety study, which enrolled young men and women, also showed a reduction in risk for both men and women who took daily TDF/FTC. However, the VOICE oral TDF arm and the FEM-PrEP study of oral TDF/FTC in women found flat results.

“We must, without any delay, accelerate the development of prevention strategies for HIV-negative women that address possible adherence issues. While we do not yet know the role that adherence to the drug regimen might have played in the FEM-PrEP and VOICE trial data to-date, we know that, for some women, strategies that require less-frequent dosing, such as a vaginal ring inserted monthly, and long-acting injectables, will be simpler to use from an adherence stand point,” Warren said.

“Simultaneously, we must make good on the promise made to all trial participants to extract every bit of valuable data that we can from the ongoing trials. We have much to learn from analyses of FEM-PrEP and VOICE as well as from FACTS 001 and the ongoing Partners PrEP trial. The prevention field must be prepared to act on emerging findings from these trials with clear plans and processes for accelerating or shelving approaches.”

“Medical research is often complicated, and we know to expect setbacks along the way. But with 2.7 million new HIV infections every year, it is imperative that we continue to look for new ways to curb the epidemic,” Warren added. “It is especially important that we focus on interventions that will help young women—who so often bear the brunt of the epidemic—protect themselves.”

“There will never be a silver bullet for HIV prevention, so we must continue to rapidly expand testing, treatment and voluntary medical male circumcision, amongst the array of evidence-based interventions, while also accelerating the research and development of additional new options, notably a range of ARV- and non-ARV-based prevention methods and vaccines to protect against HIV.”

A table of ongoing and planned ARV-based microbicide and PrEP trials is below. For more information visit www.avac.org.

A PDF version of this press release is available here.

Contact:
Mitchell Warren, [email protected], +1-914-661-1536
Kay Marshall, [email protected], +1-347-249-6375

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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.

New York, NY — Thirteen prominent U.S. HIV/AIDS organizations have issued an open letter to the U.S. Food and Drug Administration and Gilead Sciences calling for prompt regulatory review of pre-exposure prophylaxis (PrEP) for HIV prevention in gay and bisexual men and transgender women (men who have sex with men, or MSM). The letter urges FDA and Gilead to start the review process that could allow safe and appropriate approved PrEP use as a public health intervention, and not to delay review because of distinct questions about the safety and efficacy of PrEP in heterosexual populations. The letter is available online at: www.avac.org/letters/fda-gilead

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.

Advocates assert that the need for new HIV prevention strategies for MSM is urgent. The U.S. Centers for Disease Control (CDC) estimates that MSM account for more than half of all new HIV infections in the United States. CDC logged an estimated 34% increase in HIV infections in young gay men between 2006 and 2009, and a 48% HIV increase among young black/African American gay men over the same period.

“We desperately need new strategies and tools to reduce the rapidly increasing rates of HIV infection in black gay and bisexual men,” said Phill Wilson, executive director of the Black AIDS Institute. “We’ve had evidence of PrEP’s effectiveness in MSM for almost a year now. It’s time to use every tool at our disposal to reduce the 50,000 new HIV infections that occur each year in this country. Prompt FDA review will help ensure that appropriate guidelines for PrEP use are established that can reduce HIV infections and safeguard public health.”

Data on PrEP in heterosexuals raise important but unique questions that may require further study. Two major trials in Africa found that PrEP reduces HIV infection risk in heterosexual men and women substantially. But two other studies present conflicting information about how PrEP works in heterosexuals. Critical and necessary efforts to understand how PrEP interacts with hormonal contraception, or how PrEP may impact pregnancy, however, should not delay access to a potentially lifesaving form of HIV prevention for MSM.

Before the results of the heterosexual PrEP studies were announced, the FDA and Gilead Sciences, the maker of the drugs, were reported to be ready to move quickly to consider approval of PrEP for those MSM who could benefit from the approach. Recent signs indicate, however, that FDA review of PrEP for this population may not start until the agency acquires more data on PrEP among heterosexuals—despite the urgent need for new HIV prevention strategies for MSM, and the fact that PrEP data in MSM were announced nearly one year ago.

“The FDA and Gilead Sciences should move quickly to ensure a thorough review of PrEP for MSM now, while they both work simultaneously and swiftly to thoroughly address questions and concerns about PrEP among heterosexual populations,” said Mitchell Warren, executive director of AVAC “Prompt FDA review of PrEP in MSM is the right thing to do for public health. In the midst of a growing HIV epidemic, HIV prevention delayed is HIV prevention denied.”

Contact:
Kay Marshall, [email protected], +1-347-249-6375
Robert Reinhard, [email protected], +1-415-570-1010

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A PDF version of this document is available here.

RE: Timing the Review and Approval of Pre-exposure Prophylaxis for HIV Prevention

We, the undersigned, are non-profit organizations and coalitions who support the development of and access to new safe and effective HIV prevention options in the United States and globally. Data from multiple clinical trials in different populations showing that antiretroviral drugs for HIV treatment can also prevent HIV infection have accumulated to the point where FDA approval decisions could be made for this intervention. The approval issues for the different populations are not identical. For the reasons outlined below, we urge the FDA and Gilead Sciences to reconsider plans to combine the approval for a prevention indication for both men who have sex with men, including transgender populations (MSM) and heterosexuals into a single filing. The combination could unnecessarily delay approval for MSM, the group at greatest risk of HIV infection in the United States.

FDA has a duty to move forward on beneficial products by setting out best terms of use, and, by law, to “promote the public health by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in a timely manner.” This duty is what’s in question today.

Results from three large clinical trials show that oral pre-exposure prophylaxis (oral PrEP) has the potential to prevent new HIV infections. Last year the iPrEx trial found that daily TDF/FTC (marketed as Truvada by Gilead) along with standard prevention reduced HIV infection risk by 42% in at-risk gay/bisexual men and transgender women who have sex with men (MSM).

The results preceded release of important infection data for MSM in the U.S. The U.S. Centers for Disease Control (CDC) estimates that MSM account for more than half of all new HIV infections in the U. S. For many MSM the HIV risk is growing. CDC found an estimated 34% increase in HIV infections in young MSM between 2006 and 2009, and a 48% increase in HIV among young black/African American MSM over the same period. MSM represent a population with demonstrable need for effective prevention tools.

Two additional trials have shown that oral TDF/FTC (or TDF alone as in one of the trials) as PrEP also reduces HIV infection risk by 62-73% in at-risk heterosexual men and women. But a fourth study of oral TDF/FTC as PrEP, which was conducted in a population of heterosexual women, was stopped before its anticipated end date after an interim data review found equal numbers of infections in the experimental and placebo arms. More recently, the oversight board of an ongoing PrEP trial comparing oral TDF alone to oral TDF/FTC and a gel containing TDF recommended discontinuing the use of oral TDF alone in a single arm of the study. That approach was deemed unable to show efficacy in the population of heterosexual women being studied. The other arms of the study continue to evaluate the other PrEP modalities. We do not yet know why this pattern emerged in these trials. Nevertheless, combined data show oral PrEP may be a vitally important prevention tool for some heterosexual populations.

Separate safety and effectiveness questions in data collected in heterosexual groups may unduly lengthen FDA review for MSM if the two approvals are bundled together. In addition to clarity surrounding the one trial that was stopped, FDA may have questions about:

• Offering oral PrEP to women who use hormonal contraceptives concurrently;
• Balancing risks to unborn children exposed to drugs in the absence of a known risk of exposure to HIV from an uninfected pregnant mother;
• The basis of using two-drug combinations vs single drugs in heterosexual populations.

The US DHHS perinatal guidelines for HIV recently withheld recommendations for oral PrEP based on these concerns. If approval for both MSM and heterosexuals is bundled together, it may take many months to answer the questions affecting one group more than the other.

Harms result when the benefits of FDA approval are delayed for a safe and effective intervention:

• Patients do not have the benefit of the safety and control measures that come with proper labeling, study- and FDA-regulated risk management;
• FDA regulatory requirements are not able to be integrated with or to facilitate other efforts to demonstrate real world effectiveness in a cohesive organized manner;
• FDA approval spurs insurance coverage from private and public sources needed to secure equitable access for disadvantaged populations;
• The drug manufacturer will be restricted from communicating important data to clinics because of restraints on unauthorized marketing;
• While PrEP should only be given to those who can truly benefit, a delayed approval means many of them will simply not get it at all. Whichever infections could have been averted will unfortunately occur.

These harms should not be imposed on either MSM or heterosexuals. FDA’s duty also requires the Agency to safeguard patients from uncertainty, and today, unfortunately, that uncertainty possibly weighs more heavily with one group more than the other. We must shore up that uncertainty promptly but not delay access to risk-reducing tools for MSM sooner if we can. Approval delayed, like justice, is approval denied.

FDA approval also influences the availability of PrEP in other countries hardest-hit by HIV/AIDS that look to the FDA for assurance that a new therapy is safe and effective. The largest international program for HIV treatment and prevention in developing countries, PEPFAR, considers FDA approval an important step in providing programming/access to PrEP.

Before the results of heterosexual PrEP studies were announced, the FDA and Gilead were reported to be ready to move forward on a review of PrEP for MSM. Now it looks like action on PrEP for MSM may take longer. Even six months of further delay could result in many preventable new HIV infections.

The FDA and Gilead should move quickly to ensure a thorough review of PrEP for MSM. It’s time. We also urge no delay to clear up data that will help heterosexual populations in need. Useful interventions often go through sequential approvals as was the case for Gardasil to prevent HPV related cancers and lesions in young women and men. Oral PrEP is not a magic pill but it adds to the available arsenal we have to prevent HIV.

Sincerely yours,

AIDS Action Committee of Massachusetts
AIDS Foundation of Chicago
AIDS Research Consortium of Atlanta
AIDS United
AVAC
Black AIDS Institute
Fenway Health
GMHC
Harlem United
International Rectal Microbicides Advocates
National Minority AIDS Council
Project Inform
San Francisco AIDS Foundation

A PDF version of this document is available here.