Making an Impact With Preexposure Prophylaxis for Prevention of HIV Infection.

Five years ago, pivotal evidence emerged from clinical trials that preexposure prophylaxis (PrEP), using oral tenofovir disoproxil fumarate in combination with emtricitabine, was effective and safe for prevention of human immunodeficiency virus (HIV) infection [1, 2]. Subsequent work has shown high uptake and use of PrEP in demonstration settings worldwide [3–6]. Regulatory approval of a label indication by the Food and Drug Administration (FDA) in 2012 was a first for HIV prevention and has been followed more recently by similar approvals in some of the countries most heavily affected by HIV [7, 8]. PrEP works for HIV prevention, reducing individual risk by >90% [9], and early adopters are already achieving real benefits [10]. Normative guidance documents from the Centers for Disease Control and Prevention (CDC) in 2014 and the World Health Organization (WHO) in 2015 have carved out a role for PrEP as a global strategy to protect individuals at risk [11, 12]. Reducing the burden of HIV globally with PrEP and other effective strategies requires defining how to prioritize delivery for greatest impact. An important challenge for PrEP has been identifying those at risk for HIV acquisition for whom PrEP could be a prevention choice. The WHO has proposed a standard termed “substantial risk,” defined as an anticipated HIV infection incidence in the absence of PrEP of 3% per year. The FDA-approved prescription drug label in the United States notes that high-risk characteristics include involvement in a social network in which the HIV infection prevalence is high, limited use of condoms, a history of sexually transmitted infections, exchange of sex for commodities, incarceration, drug and alcohol use, and sex partners of unknown HIV status. While these definitions are helpful for resource allocation and geographic PrEP prioritization, providers need simple questions that can define those patients who would benefit from PrEP and then need to use those in a way that achieves prevention impact. In this issue of The Journal of Infectious Diseases [13], Jenness et al present a mathematical model that assesses the CDC’s recommended criteria for PrEP use in USmen who have sex with men (MSM): essentially, recent receptive or insertive anal sex, without a condom, with a partner of unknown HIV status (within or outside of a monogamous relationship) or anal sex, regardless of condom use, in an ongoing relationship with a known HIV-positive partner. The model was parameterized with sexual behavior data from US populations, realistic PrEP adherence was included based on data from recent demonstration studies, and sensitivity analyses explored a range of coverage, adherence, and time windows for behaviors. The authors found that, with 40% coverage among those meeting at-risk criteria and 62% adhering to PrEP, one third of new infections in the United States could be prevented over the next 10 years. In the Jenness et al model, the greatest contributor to new infections averted was coverage: asmore at-riskmen receive PrEP, the impact of PrEP increases. Simple behavioral criteria, such as those defined by the CDC, were designed to facilitate PrEP prescribing and, if followed, could result in substantial impact. However, the number of persons prescribed PrEP in most locales remains low from a coverage perspective, and, thus, its impact to date on the HIV epidemic, in the United States and globally, is substantially smaller than it could be. Challenges to increasing the numbers of at-risk persons who are receiving PrEP include barriers to access (to whom should PrEP be prescribed, where can it be received, and who will pay for it) and slow diffusion of awareness in priority populations. However, substantial increases in awareness have been documented, often through social media and homegrown public health campaigns. Some barriers to access (such as prescription coverage) have not been as formidable in all cases as initially expected, and public and private healthcare models for PrEP delivery have been described [10, 14, 15]. Notably, the CDC criteria are broad, which will help achieve appropriate coverage of the target population. Alternatives that limit access to PrEP to those at only the absolute highest risk might surprisingly limit its impact. For example, although the Jenness et al model did not assess recent sexually transmitted infection Received and accepted 24 May 2016. Correspondence: J. M. Baeten, Departments of Global Health, Medicine, and Epidemiology, University of Washington, Box 359927, 325 Ninth Ave, Seattle, WA 98104 ([email protected]). The Journal of Infectious Diseases © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected]. DOI: 10.1093/infdis/jiw224