May 10, 2012

F.D.A. Panel Weighs Preventive Use of H.I.V. Drug

Published: May 10, 2012

SILVER SPRING, Md. — An advisory panel to the Food and Drug Administration is expected to vote Thursday on whether a drug already used to treat H.I.V. infection should also be approved to prevent it. Such a recommendation, if made, would mark the first time that government advisers have advocated giving antiviral medicine to healthy people who might be exposed through sexual activity to the virus that causes AIDS.

Studies have shown that people who take the medicine, Truvada, every day have a greatly reduced risk of infection.

The F.D.A. usually accepts the advice of its advisory panels, which are made up of outside experts, mostly from medical schools.

On Thursday morning, the panel evaluated studies of the once-a-day pill and heard scientific presentations about whether Truvada should be prescribed for people at high risk of infection, like gay men who have multiple sex partners, especially those who do not always use condoms, and people in relationships with someone who is H.I.V.-positive. Young black men who have sex with other men are at highest risk.

The drug is meant not to replace condoms and other safe-sex measures, but to be used with them for added protection.

Experts say better methods of prevention are needed because there are 50,000 new H.I.V. infections a year in the United States. Several speakers emphasized on Thursday that that number had not budged in 15 to 20 years. Counseling and condoms are not doing the job, they said, and many of the newly infected are men whose sexual partners do not realize they are H.I.V.-positive.

Worldwide, there were 2.4 million to 2.9 million new cases in 2010.

After the scientific presentations on Thursday morning, many panelists voiced concern about the possibility that people who become infected while taking Truvada could develop dangerous drug-resistant strains of the virus. And they asked why resistance occurs in people taking the medicine, given that it is such a powerful drug.

Dr. John W. Mellors, chief of infectious diseases at the University of Pittsburgh, said that one likely reason is that if people take the pills inconsistently, they may wind up with levels of the drug that are too low to prevent infection, but just high enough to allow resistance to occur.

An F.D.A. analysis found that people who are older and more educated are more likely to take the drug faithfully. So are men who reported having receptive anal sex without condoms. There is no data to tell whether Truvada would prevent H.I.V. infection spread by needle sharing.

Nausea and abdominal pain are common side effects for the first few weeks people take Truvada; those symptoms then diminish.

Because Truvada has already been approved to treat H.I.V. infection, doctors have been free to prescribe it for prevention, and some have been doing so. Prescribing a drug for something other than its approved purpose, called off-label use, is allowed by the F.D.A, though drug companies are not permitted to market or promote drugs for such uses.

Advocates of Truvada’s use for prevention say F.D.A. approval would help ensure the drug was more safely and effectively used. The medicine would have to be labeled with specific instructions for taking it, including which lab tests patients need to get for safety reasons. For instance, patients should be tested periodically for H.I.V. infection, because if someone who is already infected takes Truvada alone, drug-resistant strains of the virus may quickly develop. Some patients may also need to have their kidney function monitored. And the drug can also cause slight decreases in bone density that may need monitoring in some people. F.D.A. approval may also make it more likely that insurers would cover preventive use, which costs about $14,000 a year.

Truvada, which contains two antiviral drugs, is sold by Gilead Sciences, based in Foster City, Calif. Though it will be used alone for prevention, it must be taken along with other antiviral to treat H.I.V. First approved in 2004, it quickly became one of the best-selling H.I.V. drugs. Gilead reported Truvada sales of $758.3 million in the first quarter of this year, which would translate into more than $3 billion a year.

A Gilead official, Dr. Andrew Cheng, told the panel on Thursday that if Truvada is approved for prevention, the company will conduct safety monitoring and provide educational materials that will emphasize the importance of using other prevention methods as well, like condoms, counseling and regular H.I.V. testing. He said Gilead would also provide other services, including free condoms and testing for H.I.V. and hepatitis B; subsidized tests for viral resistance for people who become infected; and an assistance program for people with no prescription coverage.

A number of prevention studies of Truvada have been conducted in the past few years, with somewhat mixed results. A study of 2,499 gay men in six countries, published in 2010, found an overall risk reduction of 44 percent in men for whom Truvada was prescribed. When researchers looked more closely and checked blood levels of the drug, they found that many of the men had not taken it every day. Among those who did take it correctly, the risk reduction was about 90 percent. But only about 10 percent of the men took the pills exactly as directed.

Some studies in Africa and Asia have also shown significant risk reduction among healthy people whose partners were infected. But other studies in Africa were halted because the drug was showing no benefit in women; subsequent analyses revealed that many of the women were not taking the pills, sometimes because they did not think they were at risk.

The failure of some people in the studies to take the pills every day has led the AIDS Healthcare Foundation, a medical and advocacy group based in Los Angeles, to contend that prescribing Truvada as prevention could backfire, leaving people vulnerable while lulling them into believing that sex without condoms is safe.

“You will definitely have a result that is far worse than what you had in any of the studies,” Michael Weinstein, the foundation’s president, said in an interview.

But a researcher who conducted the study in gay men, Dr. Robert M. Grant of the Gladstone Institute of Virology and Immunology, which is affiliated with the University of California, San Francisco, disagreed, likening Mr. Weinstein’s argument to that of people in the 1970s who warned that air bags in cars would lead people to stop using seat belts.

“Did that happen?” Dr. Grant asked in an interview. “No.”

He said the goal of prevention research was to provide many ways to avoid infection so that everyone was using at least two of them.

Existing methods include condoms, counseling, male circumcision and widespread use of antiviral medicines by people who are already have H.I.V., even in the early stages, because treatment has been shown to significantly reduce the odds that they will infect others.