PreExposure Prophylaxis A Narrative Review of Pr

Authors: Andrew Silapaswan Douglas Krakower Kenneth H Mayer

Publish Date: 2016/10/19

Volume: 32, Issue: 2, Pages: 192-198

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Abstract

Since FDA approval of HIV preexposure prophylaxis PrEP for HIV prevention attention has been focused on PrEP implementation The CDC estimates that 12 million US adults might benefit from PrEP but only a minority are using PrEP so there is a significant unmet need to increase access for those at risk for HIV Given the large numbers of individuals who have indications for PrEP there are not enough practicing specialists to meet the growing need for providers trained in providing PrEP Moreover since PrEP is a preventive intervention for otherwise healthy individuals primary care providers PCPs should be primary prescribers of PrEP There are important clinical considerations that providers should take into account when planning to prescribe PrEP which are highlighted in the clinical case discussed A growing body of research also suggests that some providers may be cautious about prescribing PrEP because of concerns regarding its “realworld” effectiveness anticipated unintended consequences associated with its use and ambiguity as to who should prescribe it This review summarizes findings from studies that have assessed prescriber behavior regarding provision of PrEP and offers recommendations on how to optimize PrEP implementation in primary care settings Development and dissemination of educational interventions for PCPs and potential PrEP users are needed including improved methods to assist clinicians in identifying appropriate PrEP candidates and programs to promote medication adherence and access to social and behavioral health services PCPs are wellpositioned to prescribe PrEP and coordinate healthrelated services to improve the sexual health of their patients but tailored educational programs are neededAlthough US HIV incidence has remained stable in recent years with approximately 50000 new infections annually specific populations remain disproportionately affected1 Men who have sex with men MSM bear a disproportionate burden of HIV and in 2014 accounted for 67  of new diagnoses2 Lifetime HIV incidence rates for African American and Hispanic/Latino MSM are 50 and 25  respectively2 Increasing rates of HIV incidence in MSM underscore the need for improved access to effective HIV prevention options In 2012 the US Food and Drug Administration FDA approved the oncedaily fixeddose combination of tenofovir disoproxil fumarate and emtricitabine TDFFTC for use as oral preexposure prophylaxis PrEP for HIV prevention3 Since FDA approval and publication of the Centers for Disease Control and Prevention CDC clinical practice guidelines in 2014 attention has been focused on PrEP implementation particularly by primary care providers PCPsMultiple studies have assessed provider attitudes intentions and behaviors regarding PrEP and have identified potential barriers to PrEP implementation Data on providerreported concerns have largely been gathered from HIV specialists4 infectious disease physicians5 6 and other providers in large urban centers7 – 11 Current understanding of prescriber behavior may be limited by the geographic and specialized nature of those interviewedThe following case describes the clinical history of a patient engaged in primary care in Boston Massachusetts and highlights several key clinical considerations when prescribing PrEP The subsequent review of providerreported barriers includes recommendations on strategies for increasing the rollout of PrEP in primary care Given the disproportionate burden of new HIV infections among MSM this review will focus primarily on the evidence pertaining to MSM and the sexual risk of HIV acquisitionMr A is a 49yearold man who presented for routine care with his PCP He had been in a longstanding sexual relationship with a woman who was HIVinfected and expressed concerns about his risk for HIV He engaged in condomless oral and penile–vaginal sex with his female partner twice a month His partner did not use antiretroviral medication He also reported sexual contact with men of unknown HIV status about twice per year including condomless insertive and receptive oral and anal sex Although he reported sexual activity with men he identified as heterosexual Mr A had been treated twice for sexually transmitted infections STI and was prescribed HIV postexposure prophylaxis twice after condomless sex with his female partner After a discussion about PrEP with his PCP he began PrEP after being screened for bacterial STI and found to be HIVuninfected with normal renal function and a negative hepatitis B surface antigen test findingDuring his first year of PrEP use Mr A remained HIVuninfected and did not acquire any other STIs After about 12 months of PrEP use however he discontinued PrEP after experiencing housing instability and depression Mr A’s history illustrates several challenges that providers should consider when prescribing PrEP as they may affect longterm adherence His sexual history also demonstrates how sexual identity may not be consistent with sexual behavior Although PCPs are wellpositioned to prescribe PrEP because many atrisk persons present for primary care as opposed to specialty clinics studies have found that some providers remain cautious about prescribing PrEP The following review of providerreported barriers discusses concerns regarding the “realworld” efficacy of PrEP potential concerns regarding its implementation and uncertainty as to who should be the primary prescribers of PrEP5 9 12 13 Finally recommendations on how to optimize PrEP implementation within primary care are discussedEfficacy studies have demonstrated that PrEP has the potential to prevent many HIV infections and medication adherence is critical to achieving maximal protection14 – 22 The iPrEx study a placebocontrolled randomized study of 2500 MSM and transgender women demonstrated a 44  reduction in HIV incidence in those assigned to TDFFTC and an estimated 99  reduction in those whose drug levels suggested daily adherence14 23 Efficacy estimates in other placebocontrolled studies of daily TDFFTC PrEP vary greatly with medication adherence being the major predictor of efficacy14 – 22 Some providers have cited suboptimal efficacy in several trials as a reason not to consider PrEP as a mainstay for prevention4 – 11 However participants in early studies were told they might receive a placebo and PrEP efficacy was not proven In subsequent studies when individuals were educated about the importance of adherence efficacy results were higher A randomized controlled trial of MSM accessing services in British STI clinics found that those who had access to PrEP had 86  decreased HIV incidence compared to those assigned to a wait list24 A clinicbased study of PrEP use by over 650 MSM in San Francisco found high adherence rates and no new HIV infections25 26 However PrEP adherence has remained a challenge for some individuals27 A study of young MSM aged 18 to 22 years found that adherence attenuated over time underscoring the need for ongoing medication adherence support28 Women may need more consistent daily adherence than MSM because of the slower pharmacokinetics of tenofovir accumulation in cervicovaginal tissue compared to rectal mucosa29In the IPERGAY study 414 MSM and transgender women were randomized to receive pericoital TDFFTC as PrEP or placebo15 Participants randomized to receive TDFFTC were directed to take two pills of TDFFTC 2 to 24 h prior to sexual activity followed by a third pill 24 h after the first dose and a fourth pill 24 h later Study results demonstrated an 86  reduction in HIV incidence15 Participants used an average of 15 pills per month15 so it is not known whether pericoital PrEP would confer HIV risk reduction benefits to those who have less frequent HIV exposure Despite ongoing research on pericoital PrEP and other alternative dosing regimens only daily TDFFTC is currently FDAapproved for PrEP

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