PrEP Is Safe and Effective, Even For Those Who Miss Doses

An exciting and late-breaking development at the AIDS 2014 Conference in Melbourne revealed findings published in Lancet Infectious Diseases that show that PrEP is safe and effective at preventing HIV infection, even for those who miss doses.

"Findings from iPrEx open-label extension (iPrEx OLE) are particularly important in relation to emerging guidelines recommending expanded use of PrEP," said iPrEx Protocol Chair Robert Grant, MD, MPH of the Gladstone Institutes, the University of California at San Francisco and the San Francisco AIDS Foundation. "The project provides critical insight into what happens as PrEP transitions from clinical trials to clinical practice. It is particularly compelling to see such strong interest in PrEP among young gay and bisexual men, who are increasingly impacted by HIV."

On July 22, findings from iPrEx OLE, the largest demonstration project of HIV PrEP to date, include strong ongoing evidence of PrEP effectiveness and safety, strong interest in PrEP among gay and bisexual men and transgender women at particularly high risk for HIV and no evidence of increased sexual risk behavior on the part of people taking PrEP. The data are particularly important in light of recent CDC and WHO guidelines recommending expanded use of PrEP among men who have sex with men.

"These findings are incredibly important to the continued roll-out of PrEP among gay and bisexual men, who urgently need new HIV prevention options," said AVAC Executive Director Mitchell Warren. "They increase our understanding of the dynamics of PrEP and the role it can play in reducing the risk of HIV infection. As we translate what we've learned from randomized controlled trials into meaningful public health strategies, this study begins to answer some of the long-simmering questions about how to deliver PrEP, and to whom. It's more clear than ever while PrEP is not right for everyone, it is right for some -- and is an essential component of HIV prevention."
The 72-week open label extension of iPrEx enrolled 1603 HIV uninfected persons with an average age of 28 years at 11 sites on four continents between June 2011 and June 2012. The project concluded in December 2013. All participants had previously taken part in randomized blinded placebo-controlled trials of oral PrEP. Seventy-six percent of OLE participants chose to receive once-daily oral PrEP with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), while the remainder chose to participate in the study without receiving PrEP.

Among the key study findings were that PrEP is highly effective at preventing HIV in MSM/TGW, even when some doses of the daily regimen are missed. No study participant who took PrEP 4 or more times per week became HIV-infected.

"Daily dosing of PrEP is recommended, because it helps foster the habit of consistent PrEP use and increases drug levels in the body, providing the best safety cushion for individuals who occasionally miss doses," said Grant. "At the same time, these results demonstrate that PrEP remains highly effective, even in real-world circumstances in which adherence may not be perfect."

Doctors also found a high demand for PrEP in MSM/TGW, indicating a high degree of acceptability for PrEP in this population when it is offered free of charge. Importantly, interest in and adherence to PrEP in iPrEx OLE were higher among persons at increased risk for HIV, as indicated by their likelihood to engage in receptive anal intercourse without condoms, to have more sexual partners or to have a history of syphilis or herpes.

"Encouragingly, these results indicate that people at higher risk may be more likely to seek out and to benefit from the protection that PrEP provides," said Kenneth Mayer, MD, medical research director of Boston's Fenway Institute.

The study also indicates that sustained engagement may be an important challenge for PrEP services. Substance and alcohol use were not associated with disengagement, but retention and drug concentrations were lower with younger age, indicating that some individuals who could benefit from PrEP may need additional support to use it successfully.

And despite considerable speculation that access to PrEP could cause individuals to increase their sexual risk-taking behavior, iPrEx OLE found no evidence of "risk compensation" among PrEP users. Sexual practices among both PrEP receivers and those not receiving PrEP became safer by self-report. Syphilis incidence, another important marker of sexual risk behavior, was comparable between the two groups.

"This study provides still more evidence that gay and bisexual men and transgender women want access to this safe and highly effective form of HIV prevention," said Jim Pickett, director of prevention advocacy and gay men's health at AIDS Foundation of Chicago. "Moving forward, we must increase awareness of PrEP among all who could benefit from it, and overcome critical barriers to PrEP access including misinformation, lack of provider training, and insufficient coverage via health insurance and other programs."

The U.S. Centers for Disease Control and Prevention (CDC) clinical practice guidelines recommending that health care providers consider PrEP for anyone at substantial risk of infection were issued in May 2014. And in issuing its new Consolidated Guidelines on HIV Prevention, Diagnosis and Treatment in Key Populations this month, the World Health Organization strongly recommends that MSM consider taking antiretroviral medicines as an additional method of preventing HIV infection.

"Modeling estimates that, globally, 20-25 percent reductions in HIV incidence among men who have sex with men could be achieved through pre-exposure prophylaxis, averting up to 1 million new infections among this group over 10 years," wrote the WHO.

Researchers praised the results delivered at the International AIDS Conference in Melbourne, Australia, on the "real world" use of HIV pre-exposure prophylaxis (PrEP) among gay and bisexual men who had participated in the earlier iPrEx trial.

"When these results are combined the original iPrEx study and other trials, with the FDA approval of Truvada as PrEP two years ago, and with very recent PrEP guidelines from the Centers for Disease Control & Prevention and the World Health Organization, the story is clear: PrEP is real, it works, and it should be made available to people at risk now as part of high-impact combination prevention," said Warren.