An estimated 50,000 people in the United States become infected with HIV annually. Truvada (a combination tablet containing tenofovir 300 mg plus emtricitabine 200 mg) was recently granted FDA approval for preexposure prophylaxis (PrEP) of HIV infection in carefully selected high-risk patients. PrEP is a relatively new and controversial strategy to prevent HIV transmission in people at highest risk of acquiring the virus. In 2011, the CDC released interim guidelines for HIV PrEP in men who have sex with men. These guidelines were recently updated to include recommendations for heterosexual serodiscordant couples (couples in which one partner is infected with HIV and the other partner is not infected).
WHO SHOULD RECEIVE PrEP?
The best candidates for PrEP in the United States are those in a sexual relationship with partners known to have HIV infection. Patients must understand that PrEP is not 100% effective, however, and it should not replace routine safer-sex practices. Rather, PrEP is an adjunct to a comprehensive set of prevention services, including risk reduction counseling and ready access to condoms. Medication adherence is critical, and clinicians should stress that PREP fails if adherence is poor.
WHAT DOES THE RESEARCH SHOW?
Truvada was granted FDA approval for HIV PrEP in heterosexual men and women based on the results of two randomized, double-blind, placebo-controlled trials conducted in Africa. Both trials offered risk reduction counseling to all patients, free male and female condoms, and screening and treatment of sexually transmitted infections (STIs).
The first trial that showed benefit of HIV PrEP enrolled more than 4,700 serodiscordant couples.1 The HIV-uninfected partner was assigned to Truvada, tenofovir alone, or placebo. At the time of enrollment, national guidelines prevented the HIV-infected partner from receiving antiretroviral therapy. In theory, this would represent a population at high risk of viral transmission because of unsuppressed viral loads. Couples were followed for up to 36 months. During this time, there were 13 infections in the Truvada group (0.82%), 17 in the tenofovir group (1.07%), and 52 in the placebo group (3.28%). This is a relative risk reduction of 75% with Truvada compared with placebo. Notably, of the people assigned to Truvada or tenofovir who became HIV-positive, approximately 70% had undetectable levels of medication in the blood.
In the second trial, 1,216 heterosexual men and women were assigned to either Truvada or placebo.2 Although this trial did not specifically enroll serodiscordant couples, it was conducted in Botswana, which has the world’s second highest prevalence of HIV infection. Of the 610 volunteers assigned to the Truvada group, 9 became infected with HIV (1.48%) compared with 24 of 606 people assigned to placebo (3.96%). This translates into a relative risk reduction of greater than 62%. Of the patients in the treatment arm who became infected, approximately half had no detectable medication in the blood. When medication was detectable, levels were often very low. In contrast, of the people who did not acquire infection, more than 80% had detectable serum medication, and their average blood level was much higher than in those who became infected. This highlights the importance of adherence.
Based on these trials, the FDA approved Truvada 1 tablet daily for PrEP in persons at high risk of acquiring HIV infection. This is the first drug to be approved for this use. Only persons who are confirmed to be HIV-negative immediately prior to initiating therapy can receive Truvada. Drug-resistant strains have emerged in patients who were HIV-positive and received Truvada for PrEP following undetected acute HIV infection. Therefore, anyone with signs or symptoms of acute HIV infection (fever, lymphadenopathy, rash, myalgias, malaise) should not receive Truvada. PAs should review the CDC guidelines for HIV PrEP for assistance in prescribing and monitoring therapy, particularly with special populations, such as women of childbearing age.3 Key points of these guidelines are summarized in Table 1.
Finally, the cost of PrEP is significant. The drug alone can cost more than $1,000 a month. Risks, benefits, and adherence be discussed with each patient. Providers should know that Truvada is not approved for HIV PrEP in IV drug users. JAAPA
Larissa DeDea, PharmD, BCPS, PA-C, is a clinical pharmacist with Northern Arizona Healthcare, Flagstaff, Arizona. In addition to being board certified in pharmacotherapy, she is a graduate of the Yale University PA program.
1. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399-410.
2. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367(5):423-434.
3. CDC Fact Sheet. PrEP: A new tool for HIV prevention. http://www.cdc.gov/nchhstp/newsroom/docs/2012/PrEP-FactSheet-080912-508.pdf. Published August 2012. Accessed September 5, 2012.
This article originally appeared on JAAPA