U.S. Department of Health and Human Services

Drug Therapy To Prevent HIV Infection

Researchers recently investigated whether two drugs that have been used to treat infection with HIV-1, the virus that causes AIDS, might also be used to prevent transmission of the virus. For years, a combination of drugs termed “highly active antiretroviral therapy” (HAART) has been used to treat people infected with the human immunodeficiency virus, HIV-1. The use of drugs that are part of HAART in individuals before they are exposed to HIV-1 has been considered as a possible strategy to prevent the transmission of this virus. Scientists have now examined the metabolism of two drugs used in HAART and have described their distribution in different tissues.

Because HIV-1 is often transmitted through sexual contact, it was important that the researchers accurately measure levels of the active forms of the drugs in genital and colorectal mucosal tissue. The investigators gave 15 healthy men and women a single oral dose of a combination of two antiretroviral drugs, tenofovir (TFV) disoproxil fumarate and emtricitabine (FTC), and subsequently measured the concentration of these drugs over the next 14 days in the volunteers’ blood and genital secretions, as well as in their vaginal, cervical, and rectal tissues. The drugs were detected in the blood and genital secretions for the full 14-day duration of the study and were present at higher concentration in the genital secretions, with a particularly high concentration of FTC in these samples. The biologically active metabolites of the drugs were detected in the vaginal, cervical, and rectal tissues for varying durations and at different levels. The active form of TFV was found at high levels for all 14 days of the study in rectal tissue, but was present at much lower levels in vaginal and cervical tissue. The active form of FTC was present at higher levels in vaginal and cervical tissues than in colorectal tissues, but could be detected for less than 2 days. 
The wide range of tissue exposure to an orally-administered drug reported in this study illustrates the need for more detailed studies of the pharmacology of drugs currently used to treat HIV infection as possible agents to prevent transmission of the virus. Ultimately, the success of drug therapy to prevent the spread of HIV-1 will depend on selecting the proper combination of drugs and their doses. 

Patterson KB, Prince HA, Kraft E, et al. Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Sci Transl Med 3: 112re4, 2011