Pre-exposure prophylaxis for the prevention of HIV infection: Ready for prime time

Better medication adherence = greater prophylaxis effectiveness. When adherence was ≥70%, the RR was 0.27 (95% CI, 0.19–0.39). When adherence was 40% to 70%, the RR was 0.51 (95% CI, 0.38–0.70). When adherence was ≤40%, the relative risk was 0.93 (95% CI, 0.72–1.20). Adherence was better with daily administration, as opposed to event-driven administration.

Although the combination prophylactic regimen (tenofovir plus emtricitabine) was most frequently used in the clinical trials, tenofovir alone was comparable in effectiveness.

PrEP resulted in more mild adverse effects. Patients who received PrEP were more likely to develop gastrointestinal adverse effects and renal function abnormalities when compared with patients in the control arms of the studies. These adverse effects were virtually always mild and did not necessitate discontinuation of treatment.

No increase in promiscuous sexual behavior with PrEP. Specifically, investigators did not document an increased incidence of new sexually transmitted infections (STIs) in treated patients.

PrEP did not increase adverse pregnancy outcomes. In women who became pregnant while on PrEP, and who then discontinued treatment, there was no increase in the frequency of spontaneous abortion, congenital anomalies, or other adverse pregnancy outcomes.

In addition, PrEP posed a low risk for causing drug resistance in patients who became infected despite prophylaxis. Finally, the authors found that screening instruments for identifying patients at highest risk for acquiring HIV infection had low to modest sensitivity.

My recommendations for practice

Based on the study by Chou and colleagues, and on a recent commentary by Marcus et al, I believe that the following actions are justified^1–3:

• For prophylaxis to be effective, we must identify all infected patients. Therefore, screening of asymptomatic individuals during routine health encounters is essential.
• All patients should have access to easy-to-understand information related to risk factors for HIV infection.
• Every effort should be made to promote safe sex practices, such as use of latex condoms, avoidance of sex during menses and in the presence of ulcerative genital lesions, and avoidance of use of contaminated drug-injection needles.
• All high-risk patients, as defined above, should be offered PrEP.
• To the greatest extent possible, financial barriers to PrEP should be eliminated.
• Patients receiving PrEP should be monitored for evidence of renal dysfunction. Should they become infected despite prophylaxis, they should be evaluated carefully to detect drug-resistant viral strains.
• Although PrEP is definitely effective in reducing the risk of transmission of HIV infection, it does not prevent the transmission of other STIs, such as syphilis, gonorrhea, and chlamydia.

In my practice, I administer prophyaxis on a daily basis rather than just before, or after, a high-risk exposure. This approach enhances patient adherence and, hopefully, will lead to maximum effectiveness over time. I also use the combination of tenofovir disoproxil fumarate plus emtricitabine rather than tenofovir alone because there is more published information regarding the effectiveness of the combination regimen.