What’s new with PrEP?

Issue: July 2015

ByJeff Brock, PharmD, MBA, BCIDP

Despite public health prevention measures and a plethora of information available on HIV prevention, the incidence of new HIV infections in the United States has remained around 50,000 cases each year, which indicates that new effective primary prevention approaches are needed.

In 2012, Truvada (tenofovir/emtricitabine, Gilead Sciences) became the first drug approved by the FDA for pre-exposure prophylaxis (PrEP) against HIV infection, and last year, the U.S. Public Health Service issued the first guidelines on the use of PrEP for the prevention of HIV infection.

Despite robust clinical data that PrEP drastically reduces the chance of acquiring HIV, providers have been slow to adopt this in clinical practice. The slow uptake has been due to several factors, such as the belief that prescribing PrEP to an HIV-uninfected individual will make it more likely that the person will engage in risky behaviors (eg, condomless sex), fear of antiviral resistance, and associated costs for the medication. In a study published in the April 2015 issue of HIV Specialist, which is the official magazine of the American Academy of HIV Medicine, 95% of medical providers surveyed also were worried about adherence when deciding whether or not to prescribe PrEP. This is not too surprising since most real-world PrEP trials have shown that adherence is problematic, and its efficacy is dependent upon consistent use.

Since the first PrEP guidelines were issued, new study results were released at the 2015 Conference on Retroviruses and Opportunistic Infections (CROI). The remainder of this article will provide an overview of those trials.

IPERGAY

IPERGAY is a randomized, placebo-controlled trial that focused on a novel dosing strategy for PrEP among men who have sex with men (MSM), which began in February 2012. Participants were instructed to take two tablets of tenofovir/emtricitabine (TDF-FTC) or placebo 2 to 24 hours before condomless sex was anticipated. If sexual intercourse did occur, participants were to take two additional doses 24 and 48 hours after the last pre-sex dose. If participants continued having sex, they were instructed to continue taking one pill daily until 48 hours after their last sexual experience. The number of days PrEP was taken would vary depending on the frequency of sex. By November 2014, 400 patients without HIV were enrolled. After a median follow-up of 8.8 months, the incidence of HIV infection was decreased from 6.75 per 100 patient-years in the placebo arm and 0.94 per 100 patient-years in the TDF-FTC arm, an 86% relative reduction in the incidence of HIV. Sixteen patients acquired HIV during the trial — 14 in the placebo arm and two in the TDF-FTC arm.

PROUD

PROUD is a study that evaluated the use of PrEP in a real-world setting in England between November 2012 and April 2014. In addition to assessing the effectiveness of PrEP, it also was designed to evaluate if participants would acquire more sexually transmitted infections (STIs). This open-label study enrolled MSM who attended a sexual health clinic. Patients were randomly assigned to receive daily TDF-FTC either immediately or after a deferral period of 12 months, and were followed quarterly. Based on the early demonstration of efficacy, the deferred arm was halted when the immediate group showed an 86% reduction in HIV transmission. Three HIV infections were observed in the immediate group, and 19 HIV infections were seen in the deferred group despite 174 prescriptions of post-exposure prophylaxis (PEP). Three patients in this study developed resistance to FTC, but resistance to TDF was not detected. Also, there was no difference in STIs between those in the immediate and deferred groups.

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FACTS 001

FACTS 001 is a large study conducted in Africa from October 2011 to August 2014 and enrolled 2,059 sexually active HIV-negative women aged 18 to 30 years. Participants were randomly assigned to receive either placebo or a vaginal gel containing tenofovir for use before and after sex. Of the patients enrolled, there were 123 newly diagnosed HIV infections, with 61 of the new infections in the tenofovir gel group and 62 in the placebo group. The incidence of HIV infection was 4% in each group. Compliance with gel use was measured by counting returned used applicators and tenofovir drug levels in vaginal samples at quarterly visits from 214 participants in the tenofovir group. By these measures, it appeared that participants used the gel as directed at least half of the time, but only a small portion used the gel consistently, with only 22% having tenofovir drug detected in all samples. Even though the study found no significant difference in HIV protection overall, HIV acquisition rates were lower in women who reported recent sex and had detectable tenofovir in vaginal fluids.

Efforts to explore alternative strategies from what is currently recommended in the PrEP guidelines should continue to help maximize patient adherence and decrease costs associated with its use. In the future, long-acting antivirals may become available that could be utilized for prevention. One such agent is cabotegravir (ViiV Healthcare), which is a long-acting integrase inhibitor that has been shown to prevent simian immunodeficiency virus in macaques. We also need to define the best way to use PrEP so HIV-negative individuals will be protected as much as possible. We have extensive data from clinical trials that demonstrate that PrEP can be effective in preventing HIV infection. Its use should be encouraged in high-risk patients, along with ongoing patient counseling regarding safe-sex practices and other HIV risk-reduction measures. Providers should work in conjunction with their patients to make informed decisions on the proper use of this important prevention measure.

References:
Adams LM, et al. Perspectives on Prescribing Pre-exposure Prophylaxis (PrEP) for HIV Prevention. HIV Specialist. 2015. www.aahivm.org/HIV_Specialist/upload/FINAL%20April%202015%202.pdf. Accessed June 12, 2015.
Margolis DA, et al. Curr Opin HIV AIDS. 2015;doi:10.1097/COH.0000000000000169.
McCormack S, et al. Abstract 22LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 23-26, 2015; Seattle.
Molina J-M, et al. Abstract 23LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 23-26, 2015; Seattle.
Rees H, et al. Abstract 26LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 23-26, 2015; Seattle.
US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States - 2014. www.cdc.gov/hiv/pdf/PrEPguidelines2014.pdf. Accessed June 12, 2015.

For more information:
Jeff Brock, PharmD, MBA, AAHIVP, is an infectious disease pharmacy specialist at Mercy Medical Center in Des Moines, Iowa. He can be reached at: JBrock@mercydesmoines.org.

Disclosure: Brock reports no relevant financial disclosures.