In the wake of the iPrEx study, the CDC offers some general guiding principles for the implementation of pre-exposure prophylaxis.
The iPrEx study recently demonstrated proof-of-principle for the efficacy of oral chemoprophylaxis in preventing HIV infection among men who have sex with men (MSM). Daily tenofovir/FTC (Truvada) was associated with a 44% reduction in the risk for HIV acquisition, relative to placebo; efficacy was strongly associated with medication adherence (JW AIDS Clin Care Nov 23 2010). These results are tremendously exciting, but many questions remain about the appropriate use of pre-exposure prophylaxis (PrEP) in real-world clinical settings. On January 28, 2011, the CDC offered some interim guidance.
The key points are as follows:
- PrEP should be considered for use only in MSM who are at ongoing high risk for HIV acquisition.
- PrEP candidates should undergo conventional HIV antibody testing to ensure that they are HIV-negative. Those with signs or symptoms of acute HIV infection should undergo viral-load testing or nucleic acid amplification testing (NAAT). All candidates should be screened for other sexually transmitted infections (STIs) and for hepatitis B.
- Tenofovir/FTC, dosed at 1 tablet daily, is the only currently recommended PrEP regimen. It should not be used in people with creatinine clearance <60 mL/minute.
- PrEP should be prescribed for only 3 months at a time, to ensure appropriate follow-up.
- Every 2 to 3 months, PrEP recipients should receive HIV antibody testing, counseling regarding risk reduction and medication adherence, and assessment for possible signs and symptoms of STIs. STI testing should be conducted every 6 months. Serum creatinine levels should be assessed 3 months after PrEP initiation and then yearly.
- HIV antibody testing should be performed at discontinuation of PrEP.
Comment: These guidelines provide basic recommendations for clinicians who are interested in implementing PrEP based on the data that are currently available. The recommendation for follow-up every 2 to 3 months is clearly a concession to the reality that monthly follow-up (as was done in iPrEx) is unlikely to be feasible or practical outside the research setting. Many prevention experts will also take issue with the instruction to provide baseline viral-load testing and NAAT only to candidates who are clinically symptomatic; in the iPrEx study, investigators inadvertently enrolled 10 individuals with acute HIV infection, presumably because they were asymptomatic. Given the resistance consequences of missing such infection, one could argue that if an individual is at sufficient risk to warrant PrEP intervention, he should be screened at baseline with both HIV antibody testing and viral-load testing or NAAT. Alternatively, the fourth-generation HIV test that involves both antigen and antibody detection could be employed as a compromise between sensitivity and cost for detection of acute infection. More formal PrEP guidelines from the U.S. Department of Health and Human Services and the FDA are eagerly anticipated and are likely to include guidance on the type of provider that should be prescribing PrEP, application to other populations, and longer-term safety follow-up.
— Raphael J. Landovitz, MD, MSc
Dr. Landovitz is Assistant Professor, Division of Infectious Diseases, Center for Clinical AIDS Research and Education, University of California, Los Angeles. He reports no conflicts of interest.
Published in Journal Watch HIV/AIDS Clinical Care February 14, 2011