HIV/AIDS Organizations Tell FDA and Gilead Sciences: Don't Delay HIV Prevention for Gay and Bisexual Men and Transgender Women

Oct 18, 2011, 13:13 ET from AVAC

NEW YORK, Oct. 18, 2011 /PRNewswire-USNewswire/ -- 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:

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."

October 18, 2011

An Open Letter to the U.S. Food and Drug Administration and Gilead Sciences

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
Black AIDS Institute
Fenway Health
Harlem United
International Rectal Microbicides Advocates
National Minority AIDS Council
Project Inform
San Francisco AIDS Foundation