Public-health workers in Thika, Kenya, perform a skit to advertise a prophylactic HIV drug trial.Partners PrEP study
When the US Food and Drug Administration approved Viagra in 1998, officials never considered one possible side effect of the drug: higher rates of sexually transmitted diseases among men who, thanks to Viagra, would become more sexually active. A powerful tool in the fight against HIV is raising similar questions about the possibility of unintended public-health consequences if drugs are approved for use in healthy people and cause them to alter their behaviour.
Several studies in the past year have reported that the very drugs used to treat people with HIV can also stop healthy people from becoming infected (see table). But people taking the drugs may adopt riskier behaviours because they feel protected — a phenomenon known as 'risk disinhibition' — undermining the benefit of the drugs and potentially infecting others. Moreover, those who become infected while taking the preventive regimen might develop drug-resistant viruses that they could then transmit to others. "You have this wonderful scientific breakthrough," says Kevin Frost, chief executive of the Foundation for AIDS Research in New York City. "But what are the practical implications?"
Researchers will mull over these issues on 19 August at a meeting convened by the Forum for Collaborative HIV Research in Washington DC. The questions have become more urgent since January, when the drug firm Gilead of Foster City, California, announced that it plans this year to ask the Food and Drug Administration (FDA) to approve its HIV drug Truvada for use in healthy people — in what is known as pre-exposure prophylaxis, or PrEP. Truvada, which contains the antiretroviral drugs tenofovir and emtricitabine, has been used in many of the PrEP trials. In the three clinical trials that have reported benefits for PrEP so far, once-a-day pills have cut a person's risk of acquiring HIV by between 44% and 73%, a variation that is due primarily to differences in how strictly patients stuck to the daily regimen. Although the need for PrEP is greatest in poor countries, approval in the United States could greatly expand the market for Truvada, which generated US$2.65 billion in sales last year.
But asking the FDA to evaluate questions about risk disinhibition and drug resistance might push the agency into uncharted territory. "When you're talking about a population issue, is that something that the FDA should be looking at at all?" asks Jur Strobos, deputy director of the Forum for Collaborative HIV Research.
The clinical trials don't offer clear guidance. Some of the successful trials found that people on PrEP actually used condoms more frequently while receiving PrEP treatment, countering the risk-disinhibition argument. And only a few instances of drug resistance occurred, and these did not compromise patients' treatments.
“You have this wonderful scientific breakthrough. But what are the practical implications?”
But the controlled setting of a clinical trial, in which participants received intensive prevention counselling and were tested monthly for HIV, is very different from the real world. "We think of PrEP as a pill, but we all recognize that PrEP is about a much broader programme," says Mitchell Warren, director of the AIDS Vaccine Advocacy Coalition in New York City. "How you would deliver the kind of testing and monitoring that would go into that programme is a very important question."
The US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, has recommended testing patients for HIV before they begin taking the drugs and again at two- to three-month intervals. The FDA could also require drug companies to set up a registry of patients taking the drugs and ask that patients provide proof of a negative HIV test before getting their medications refilled.
Deciding who to treat with PrEP could also be a challenge. The CDC reported on 3 August that rates of new HIV infection in the United States are stable overall, but are rising in young men who have sex with men. Yet if these men aren't using the prevention measures already available, there's little reason to think doctors will have an easier time convincing them to take a daily pill.
The question of who should get PrEP is more difficult in many developing nations, which cannot even afford to treat everyone currently infected with HIV. PrEP would cost hundreds of dollars per patient per year in developing countries, and many thousands of dollars in rich nations.
Even with regimens costing less than a dollar a day, developing nations will be forced to choose between providing more treatment for those who already need it and potentially preventing new infections. Myron Cohen, a doctor and researcher at the University of North Carolina at Chapel Hill, points out that half of young girls in some parts of sub-Saharan Africa become infected with HIV by their mid-twenties. "That's unacceptable, so I see that as one potential population for PrEP," says Cohen.
Although the cost-effectiveness of PrEP increases in higher-risk populations, it will be politically dicey for financially strapped countries to justify distributing drugs to those in these groups. "Even if you thought the best use of the pills would be for sex workers, it would be very difficult to take a limited supply of pills and give them to high-risk populations at the expense of people who are dying of infection," says Cohen