New data emerges on use of pre-exposure prophylaxis (PrEP)
No link seen between regimen use and increased sexual risk behavior
Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (Truvada, Gilead Sciences, Foster City, CA) has proven effective in HIV prevention in high-risk groups, with the Food and Drug Administration approving such indication for emtricitabine's use in 2012.
While the Centers for Disease Control and Prevention (CDC) has provided interim guidance for PrEP use, a national survey of infectious disease physicians shows only 9% have prescribed it.1 Those numbers might change; just-published data indicates that there is no link between use of the PrEP regimen and increased sexual risk behavior.2
The findings build upon data from the 2010 Global Pre-exposure Prophylaxis Initiative (iPrEx) clinical study, which reported that emtricitabine, originally approved to treat HIV-positive patients, also was effective in preventing new infections in people likely to come in contact with the virus.3 A 2012 follow-up study bolstered such findings, with data suggesting that taking emtricitabine regularly reduced risk of HIV infection by more than 90%.4 (To read Contraceptive Technology Update's latest coverage of PrEP research and protocols, see "Check interim guidance for PrEP in men, women," October 2012, p. 113.)
Biological markers eyed
Questions have been raised whether taking the drug regimen could lead to a behavioral effect called risk compensation, whereby individuals adjust their behavior in response to a change in their perceived level of risk. While participants in the iPrEX trial self-reported decreases in sexual risk behavior over the course of the study, scientists involved in the current analysis decided to examine those findings more closely by studying biological markers of risk behavior.
To perform the study, investigators assessed sexual practices at baseline and quarterly thereafter; perceived treatment assignment and PrEP efficacy beliefs were assessed at 12 weeks. Among participants with one or more follow-up behavioral assessment, sexual behavior, syphilis, and HIV infection were compared by perceived treatment assignment, actual treatment assignment, and perceived PrEP efficacy.
Overall, acute HIV infection and syphilis decreased during follow-up. Compared with participants believing they were receiving placebo, participants believing they were receiving emtricitabine/tenofovir disoproxil fumarate reported more receptive anal intercourse partners prior to initiating drug (12.8 vs. 7.7, P = 0.04). Belief in receiving the study drug protocol was not associated with an increase in receptive anal intercourse with no condom from baseline through follow-up (risk ratio [RR] 0.9, 95% confidence interval [CI]: 0.6-1.4; P = 0.75), nor with a decrease after stopping study drug (RR 0.8, 95% CI: 0.5-1.3; P = 0.46). In the placebo arm, there were trends toward lower HIV incidence among participants believing they were receiving the study drug protocol (incidence rate ratio [IRR] 0.8, 95% CI: 0.4-1.8; P = 0.26) and also believing it was highly effective (IRR 0.5, 95% CI: 0.1-1.7; P = 0.12).2
"Our results suggest that HIV prevention strategies such as Truvada don't result in risk compensation because they provide an opportunity for participants to actively engage in and reduce their risk of HIV infection," says Robert Grant, MD, MPH, professor at the University of California, San Francisco and an investigator in the university-affiliated Gladstone Institutes. "Engagement, which also includes counseling, provision of condoms, and management of other sexually transmitted infections leads to motivation, which comes at a time when motivation for preventing new HIV infections is vital to curbing the spread of this worldwide epidemic."
Who's using protocol?
The CDC offers support on PrEP use at its site, http://1.usa.gov/1fzbtkI. (See other resource information at end of this story.) The interim guidance includes information for injecting drug users, heterosexually active adults, and men who have sex with men. However, clinicians are slow to embrace PrEP, results of a national survey show.1
Maile Karris, MD, assistant professor of medicine in the Division of Infectious Diseases, Department of Medicine, at University of California San Diego, and lead author of the current paper, says, "I personally have been a proponent of PrEP, but upon talking to colleagues, I found a great deal of differences in opinions and practices just within our San Diego HIV community. This led me to wonder how PrEP opinions and practices truly differed among infectious diseases physicians across the country and what clinical practice factors contributed to those views."
Karris and the research team surveyed adult infectious disease physicians from a national network about their opinions and current practices of PrEP. While most clinicians supported PrEP, only 9% had provided it. Despite CDC guidance, PrEP practices were variable and clinicians reported many barriers to its real-world provision, survey findings indicate.
An analysis of the actual use of tenofovir/emtricitabine was presented at the 2013 Interscience Conference on Antimicrobial Agents and Chemotherapy. It drew data from a nationally representative patient database, as well as information from more than 50% of the dispensing pharmacies in the United States, and applied an algorithm to exclude the use of tenofovir/emtricitabine for any other reason but as PrEP.5
A total of 1,774 individuals were prescribed PrEP between January 2011 and March 2013, the data shows. Half of the users of tenofovir/emtricitabine for PrEP were women; 32% of users were in the South, with 24% in the Northeast and West, and 18% in the Midwest. PrEP prescribers were mainly primary care providers, including emergency department clinicians; infectious diseases specialists accounted for just 12% of prescriptions.5
A coalition of more than 50 women from leading AIDS and women's health organizations is looking to U.S. government agencies to coordinate a national agenda for more information on how PrEP can best be made available as to more women at risk of HIV infection. The U.S. Women and PrEP Working Group issued the call to government officials following release of data at the 2013 Conference on Retroviruses and Opportunistic Infections showing that none of three interventions tested in a large scale trial among African women, known as VOICE (Vaginal and Oral Interventions to Control the Epidemic) daily oral tenofovir, daily oral tenofovir/emtricitabine, and daily 1% vaginal tenofovir gel provided additional protection against HIV.6
Male and female condoms are "wonderful" HIV prevention options that work for many women and their partners, observed Erika Aaron, RN, CRNP, MSN, assistant professor in the Division of Infectious Diseases and HIV Medicine at Drexel University School of Medicine in Philadelphia, in a statement released by the U.S. Women and PrEP Working Group. However, some women feel that they can't insist their partners use condoms, and many young women and their HIV-positive partners want to have children, Aaron said.
"Those women need other options to protect themselves from HIV; PrEP can help them stay HIV-negative," she stated. "We have a moral imperative to find ways to make it available to women who need it and who can use it."
- Karris MY, Beekmann SE, Mehta SR, et al. Are we prepped for preexposure prophylaxis (PrEP)? Provider opinions on the real-world use of PrEP in the United States and Canada. Clin Infect Dis 2013; doi: 10.1093/cid/cit796.
- Marcus JL, Glidden DV, Mayer KH, et al. (2013) No evidence of sexual risk compensation in the iPrEx trial of daily oral HIV preexposure prophylaxis. PLoS ONE 2013; 8(12): e81997.
- Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. NEJM 2010; 363(27):2,587-2,599.
- Anderson PL, Glidden DV, Liu A, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med 2012; 4:151ra125.
- Mera RM, Rawlings MK, Pechonkina A, et al. Status of Truvada (TVD) for HIV pre-exposure prophylaxis (PrEP) in the United States: an early drug utilization analysis. Presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy. Denver; September 2013.
- Marrazzo J, Ramjee G, Nair G, et al. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/emtricitabine, or vaginal tenofovir gel in the VOICE Study (MTN 003). 20th Conference on Retroviruses and Opportunistic Infections. Atlanta; March 2013.
- AVAC, a New York City-based non-profit organization uses education, policy analysis, advocacy, and a network of global collaborations to accelerate the ethical development and global delivery of AIDS vaccines, male circumcision, microbicides, PrEP, and other emerging HIV prevention options as part of a comprehensive response to the pandemic. It maintains a web site, www.prepwatch.org, which serves as a clearinghouse for information on PrEP for HIV prevention. PrEP Watch includes information on data, additional research, cost, access, and advocacy efforts in the United States and across the globe.