The drug company Gilead Sciences has applied to the Food and Drug Administration (FDA) to allow the drug Truvada to be prescribed to prevent HIV-1 infection. Truvada was approved to treat HIV-1 infection in 2004.

Truvada consists of two antiviral agents (Emtriva and Viread). If approved, it would be the first drug ever to prevent, or at least reduce the risk of, acquiring HIV, an approach called pre-exposure prophylaxis or PrEP.

According to the CDC, each year some 50,000 people are newly infected with HIV in the U.S. The rate of new HIV infections has remained steady for many years. More than half of these occur among men who have sex with men, nearly a quarter occur among women.

If the FDA does approve Truvada to prevent HIV infection it will probably be indicated just for those at high-risk of HIV exposure.

The first PrEP clinical study was the iPrEx study. iPrEx was conducted among high-risk HIV-negative men who have sex with men. That trial showed that once-daily use of Truvada reduced the risk of acquiring HIV by 44 percent. However, Truvada was up to 73 percent effective in preventing HIV infection for those who took the pill at least 90 percent of the time. Among men who took it enough to have the drug detectable in their body, the risk was reduced by more than 90 percent.

In July 2011, a study of heterosexual African couples in which one partner was infected with HIV and the other was not showed Truvada reduced their risk of acquiring HIV by 73 percent.

“The data from these large-scale clinical trials suggest that Truvada may have a role to play in meeting the urgent public health need to reduce new HIV infections,” said John Martin, PhD, of Gilead Sciences.

Studies done with women were not as successful however. The FEM-PrEP pill study was stopped in April 2011 when it showed Truvada had little efficacy protecting HIV-negative African women. The reason for this outcome are not yet understood.

“There may also be biological explanations for gender differences in the efficacy of oral PrEP. Vaginas and anuses are just plain different and the ways in which drugs reach and remain active in the tissues of these orifices are not the same.” noted David Alain Wohl, M.D. of The

An analysis of the FEM-PrEP data is currently underway but there are still other concerns and questions about a pill that protects against HIV infection.

One is whether the PrEP pill will provide a false sense of security that could undermine safe sex practices (condom use and safe sex counseling were components of the PrEP studies). Meanwhile, recent CDC data shows that in the U.S. alone, more than seven out of 10 of those with HIV are either not on optimal treatment or they are unaware they are infected. That makes many of them potentially infectious. But that is also the rationale being made by many for PrEP approval.

Also, if the PrEP pill is approved, will HIV uninfected individuals regularly take HIV anti-retrovirals, a group of drugs many think of as being toxic. The PrEP drugs are not without side effects, although Truvada’s toxicities in the PrEP studies appeared to be mild, at least over the short-term.

Others may opt out of seeking prescription coverage for PrEP for fear of red flagging insurance providers that they may be within a high risk group. That is if their insurance will cover PrEP.

With other PrEP studies ongoing, HIV pre-exposure prophylaxis may be inevitable. Many still feel it will be a useful HIV prevention tool, especially for communities and parts of the world where the epidemic is running rampant.

“It is clear that new prevention strategies are urgently needed to tackle the unacceptably high number of new HIV infections in the U.S.,” said Robert Grant, MD, MPH, of the Gladstone Institute and an investigator in the iPrEx trial. “It is exciting to consider the prospect of a new intervention that, when offered with condoms and other preventative measures, can help to further reduce the individual risk of HIV acquisition and the community impact of the disease.”

A decision by the FDA on the drug application for PrEP is anticipated sometime in the summer. : :