What are the ideal drugs for preexposure prophylaxis (PrEP) for HIV?

Updated: Oct 08, 2019
  • Author: Alejandro Delgado, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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The ideal chemoprophylactic agent should have a long half-life, achieve high concentrations in monocytes macrophages and genital secretions, have a high barrier for genetic resistance, and should be safe and inexpensive. The most widely studied ARV for PrEP, tenofovir DF, has many of these desirable characteristics. Most of the current clinical trials of PrEP involve tenofovir with or without emtricitabine. However, concerns exist that widespread use of PrEP could result in the selection and transmission of drug-resistant strains. Protease inhibitors are highly protein bound and achieve lower concentrations in the genital tract than tenofovir. [8] Maraviroc, an oral CCR5 co-receptor antagonist, achieves good genital and rectal concentrations and could be a potential candidate drug for PrEP.

The optimal number of drugs for chemoprophylaxis is unknown. The potential advantages of using a single agent include simplicity, lower risk of drug toxicity, and cost. These should be weighed against the risk of drug resistance if HIV infection occurs despite prophylaxis. If more than one drug is used for preexposure prophylaxis, they should work at different stages of the viral life cycle and have a higher genetic barrier to infection to decrease the risk of drug resistance.

On July 16, 2012, the FDA approved the antiretroviral combination of emtricitabine/tenofovir DF (Truvada), along with safe sex practices for PrEP to reduce the risk of sexually acquired HIV-1 in adults at high risk. As a condition of approval, the FDA is requiring Truvada’s manufacturer, Gilead Sciences, to study those who acquire HIV while taking emtricitabine/tenofovir to determine if anyone can develop a resistance to the drug. The company also needs to collect data on women who become pregnant while taking the drug since safety risks to the fetus remain unknown.

Since the initial publication of guidelines recommending the combination of emtricitabine and tenofovir disoproxil as the agent of choice for PrEP, tenofovir alafenamide (TAF) has become one of the drugs of choice for treatment of active HIV disease, given its more favorable side-effect profile. Daily administration of emtricitabine 200 mg plus tenofovir alafenamide (AF) 25 mg (Descovy) was approved in October 2019 for at-risk adults and adolescents for HIV-1 pre-exposure prophylaxis (PrEP) to reduce the risk of HIV-1 infection from sex, excluding those who have receptive vaginal sex. [9]

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