Data from iPrEx Open-Label Extension (OLE) Demonstrate High Interest in PrEP, Longer-term Evidence of Safety and Efficacy, and No Sign of Increased Risk Behavior Among PrEP Users

MELBOURNE, Australia, July 22, 2014 /PRNewswire-USNewswire/ -- Oral HIV pre-exposure prophylaxis (PrEP) provides a high degree of protection against HIV infection, even for individuals who miss some daily doses, according to new data from iPrEx OLE, the first PrEP demonstration project to report outcomes. PrEP was first proven effective in the original iPrEx study in 2010, and approved by the US FDA in 2012.

iPrEx OLE adds additional, long-term data to the growing body of evidence that PrEP for HIV prevention is safe. The project also found high interest in and willingness to use PrEP among men and transgender women who have sex with men (MSM/TGW), with greater interest in and use of PrEP among participants at higher risk for HIV, and no evidence of increased sexual risk taking among MSM/TGW using PrEP.

US 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. In issuing its new Consolidated Guidelines on HIV Prevention, Diagnosis and Treatment in Key Populations this month, The World Health Organization (WHO) stated, "WHO strongly recommends men who have sex with men consider taking antiretroviral medicines as an additional method of preventing HIV infection (pre-exposure prophylaxis)." WHO added, "Modeling estimates that, globally, 20-25% 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."

"Findings from 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."

The 72-week open label extension of iPrEx enrolled 1603 HIV uninfected persons with an average age of 28 years at 11 sites on 4 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 (76%) 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 presented here:

Effectiveness

iPrEx OLE found 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. The study measured participant use of PrEP in dried blood spots (DBS), a novel and highly sensitive biomarker of long-term PrEP use discovered and developed at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences.

Among those receiving PrEP in iPrEx OLE, HIV incidence was 4.7/100PY if drug was not detected in DBS, 2.3/100PY if drug concentrations indicated use of fewer than 2 tablets per week, 0.6/100PY for use of 2 to 3 tablets per week, and 0/100PY for use of 4 or more tablets per week (P<0.0001). There were no infections at visits where DBS sampling indicated use of 4 to 7 tablets per week. The DBS concentration associated with 90% reduced risk of HIV acquisition was consistent with use of 2 to 3 tablets per week. 

"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 Dr. 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." 

Interest and Use

Demand for PrEP was strong in this large cohort of 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.

While interest in PrEP was high among MSM/TGW in iPrEx OLE, 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.

Behavior

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 payor programs."

About the Project
iPrEx OLE was an open-label observational study of 1,603 men and transgender women who were offered PrEP for 72 weeks. The study was conducted at sites in Lima and Iquitos, Peru; Guayaquil, Ecuador; Rio de Janeiro and Sao Paulo, Brazil; San Francisco, Chicago and Boston, U.S.; Cape Town, South Africa; and Chiang Mai, Thailand. The study was sponsored by the National Institutes of Health. PrEP drug was donated by Gilead Sciences.

Embargoed copies of the iPrEx OLE manuscript, "Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study" are available through The Lancet journals press office: [email protected]; +44 (0) 207 424 4249. 

Contact
New York: Mark Aurigemma 
646-270-9451; [email protected]
Melbourne: Pedro Goicochea
415-490-8350; [email protected]

Photo - http://photos.prnewswire.com/prnh/20140722/129143

SOURCE San Francisco AIDS Foundation