Preexposure Prophylaxis for HIV Infection

ON JULY 16, 2012, THE US FOOD AND DRUG Administration (FDA) approved a daily oral antiretroviral drug to reduce the risk of sexual acquisition of human immunodeficiency virus (HIV) infection by uninfected adults. Emtricitabine/ tenofovir disoproxil fumarate (marketed by Gilead as Truvada) contains 2 nucleoside analogue HIV-1 reverse transcriptase inhibitors. Initially approved in 2004 to treat HIV infection in combination with other antiretroviral medications in people 12 years of age and older, emtricitabine/ tenofovir costs about $13 900 a year in the United States for a year of treatment. Preexposure prophylaxis, the treatment of an uninfected person before having sexual contact with an HIV-infected partner, is a widely anticipated advance that should help some people who are not infected with HIV but at high risk of infection to remain uninfected. Preexposure prophylaxis differs from another recent and complementary approach, known as treatment for prevention, which is the treatment of an HIVinfected person with antiretroviral agents to reduce the viral load and infectiousness, and thus the risk of transmission to an uninfected partner. Worldwide, about 2.5 million new HIV infections occur each year, primarily in heterosexual adults. Many people with HIV infection who are in ongoing relationshipshavepartnerswhoarenot infected, andasubstantialnumber of the new infections occur within such serodiscordant couples. In the United States, there are an estimated 50 000 new HIV infections each year, about three-fifths of which occur in men who have sexual contact with men. Preexposure prophylaxis with emtricitabine/tenofovir, however, is not a panacea for HIV infection. Taken every day, the drug reduces, but does not eliminate, the risk of acquiring HIV. It is not an effective morning before pill or morning after pill, to be taken as needed by uninfected persons. It is not a replacement for condoms and other safe sex practices, although some people may mistakenly assume this or wish that it was. Common adverse reactions in people who take the drug to prevent HIV infection include headache, abdominal pain, and weight loss. Safety concerns include impairment of kidney and liver function and decreases in bone mineral density. The long-term safety of the drug in healthy people is unknown because the available studies have only lasted for several years. Cost is also an issue, particularly for people without insurance to pay for the medication and in countries with limited resources. Preexposure prophylaxis for HIV requires that uninfected persons ingest a potent antiretroviral agent on a strict schedule, perhaps for an indefinite period of time, while following a comprehensive prevention strategy, including regular testing for HIV and other sexually transmitted diseases, consistent and correct condom use, and knowing one’s HIV status and that of partner or partners. In real life, fulfilling these requirements is a lot easier said than done. Frank discussions are needed between physicians and patients before prescribing the drug and between sexual partners. However, only an estimated 40% of people with HIV infection worldwide, and an estimated 80% of those in the United States, know their HIV status. Many people who know their status have neither disclosed their HIV status to their partners nor learned their partner’s status. Although FDA approval of emtricitabine/tenofovir for preexposure prophylaxis was expected, the considerations were complex and challenges exist. The critical questions include whether the drug will be prescribed appropriately to uninfected persons, and whether it will be used safely and properly. The updated prescribing information states that the drug “must only be prescribed to individuals confirmed to be HIVnegative immediately prior to initiating and periodically (at least every three months) during use.” Not only is emtricitabine/tenofovir less effective when doses are missed, but drugresistant HIV viruses may develop when people become infected while taking the medication for prophylaxis. Drug resistance has implications for the subsequent treatment of the infected person, as well as others who may acquire the strain. The FDA did not require that people show proof of testing negative for HIV before receiving their prescriptions as critics of the decision, such as the AIDS Healthcare Foundation, suggested. Although such a requirement might have enhanced the correct use of the medication, it might also have decreased access for those who might benefit. The FDA action was based on the results of 2 large randomized, double-blind, placebo-controlled trials and the rec-