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PURPOSE OF REVIEW: In 2019, the U.S. government launched an initiative to decrease new HIV infections by 90% over the next decade. Studies have demonstrated the efficacy of HIV preexposure prophylaxis (PrEP) for high-risk populations, and the United States Preventative Services Task Force has issued a draft grade A recommendation for PrEP, indicating substantial net benefit. However, questions have been raised about the effectiveness of PrEP in clinical settings and whether PrEP use might promote antiretroviral drug resistance and increased sexual risk behaviors, which could increase transmission of bacterial sexually transmitted infections. In this narrative review, we summarize recent evidence of the effectiveness of PrEP when provided in clinical and community settings, the emergence of antiretroviral drug resistance during PrEP use, and associations between PrEP use and increased sexual risk behaviors. We also review novel PrEP modalities that are being developed to optimize PrEP acceptability, adherence, and effectiveness. RECENT FINDINGS: Studies suggest that PrEP is effective when provided in clinical settings. However, PrEP uptake and impact have been limited in the U.S. thus far, and major disparities in access to PrEP exist. In addition, there is evidence that drug resistance can occur with PrEP use, particularly with inadvertent PrEP use during undiagnosed acute HIV infection. Risk compensation can also occur with PrEP use and has been associated with increased sexually transmitted infections. Promising new modalities for PrEP could expand options. SUMMARY: PrEP has strong potential to decrease HIV incidence. However, disparities in access must be addressed to ensure equity and impact for PrEP. While drug resistance and risk compensation can occur with PrEP use, these are not valid reasons to withhold PrEP from patients given its substantial protective benefits.

IntroductionAn estimated 1.2 million Americans have indications for using antiretroviral pre‐exposure prophylaxis (PrEP) to prevent HIV acquisition. For many of these at‐risk individuals, the best opportunity to learn about and receive PrEP will be during routine visits to their generalist primary care clinicians. However, few generalist clinicians have prescribed PrEP, primarily because of practical concerns about providing PrEP in primary care settings. The experiences of specialized primary care clinicians who have prescribed PrEP can inform the feasibility of PrEP provision by generalists.MethodsDuring January to February 2015, 35 primary care clinicians at a community health centre in Boston that specializes in the care of sexual and gender minorities completed anonymous surveys about their experiences and practices with PrEP provision. Responses were analyzed with descriptive statistics.Results and discussionThirty‐two clinicians (response rate=91%) completed the surveys. Nearly all clinicians (97%) had prescribed PrEP (median 20 patients, interquartile range 11–33). Most clinicians reported testing and risk‐reduction counselling practices concordant with U.S. Centers for Disease Control and Prevention guidelines for PrEP. Clinicians indicated that patients using PrEP experienced medication toxicities infrequently and generally reported high adherence. However, some clinicians' practices differed from guideline recommendations, and some clinicians observed patients with increased risk behaviours. Most clinicians (79%) rated PrEP provision as easy to accomplish, and 97% considered themselves likely to prescribe PrEP in the future.ConclusionsIn a primary care clinic with specialized expertise in HIV prevention, clinicians perceived that PrEP provision to large numbers of patients was safe, feasible and potentially effective. Efforts to engage generalist primary care clinicians in PrEP provision could facilitate scale‐up of this efficacious intervention.

IntroductionAfter the initial approval of the use of tenofovir disoproxil fumarate‐emtricitabine (TDF/FTC) by the US Food and Drug Administration in 2012 for anti‐HIV pre‐exposure prophylaxis (PrEP), uptake was initially limited, but more recent community surveys and expert opinion suggest wider acceptance in some key populations.DiscussionDemonstration projects are underway to determine the best practices in the United States to identify at‐risk individuals in primary care and sexually transmitted disease clinics who could benefit from PrEP. Studies of PrEP in combination with behavioural interventions are being evaluated. Studies to evaluate the use of PrEP by HIV‐uninfected women in HIV‐discordant couples interested in safe conception are also getting underway. The optimal deployment of PrEP as part of a comprehensive national HIV/AIDS strategy in the United States has been limited by lack of knowledge among some at‐risk people and by some medical providers indicating that they do not feel sufficiently knowledgeable and comfortable in prescribing PrEP. Studies are underway to determine how to assist busy clinicians to determine which of their patients could benefit from PrEP. Although most federal health insurance programmes will cover most of the costs associated with PrEP, underinsured patients in states that have not enacted health reform face additional challenges in paying for PrEP medication and appropriate clinical monitoring.ConclusionsPrEP implementation in the United States is a work in progress, with increasing awareness and uptake among some individuals in key populations.

AbstractIntroductionDiscontinuations of HIV preexposure prophylaxis (PrEP) by at‐risk individuals could decrease the effectiveness of PrEP. Our objective was to characterize patterns of, reasons for, and clinical outcomes associated with PrEP discontinuations in primary care.MethodsWe conducted medical chart reviews for patients prescribed PrEP during 2011 to 2014 at a Boston community health centre specializing in healthcare for sexual and gender minorities. Patients were followed through 2015. We characterized patients' sociodemographics, relationship status, behavioural health conditions, patterns of and reasons for PrEP discontinuations, and HIV seroconversions. Cox proportional hazards models were used to assess patient factors associated with PrEP discontinuations.ResultsOf the 663 patients prescribed PrEP, the median age was 33 years, 96% were men who have sex with men (MSM) and 73% were non‐Hispanic white; 40% were in committed relationships and 15% had HIV‐infected partners. Patients either used PrEP continuously (60%), had 1 or more discontinuations (36%), or did not initiate PrEP (4%). Discontinuations were most often due to a decrease in HIV risk perception (33%), non‐adherence to care plans (16%), or insurance barriers (12%). Of the 7 (1.1%) PrEP patients diagnosed with HIV, 1 was HIV‐infected at baseline, 2 seroconverted while using PrEP, and 4 seroconverted after discontinuations. In a multivariable model adjusted for race/ethnicity, relationship status, substance use disorders, and insurance status, those who were less than 30 years old (aHR 2.0, 95% CI 1.4 to 2.9 for ages 18 to 24, aHR 2.2, 95% CI 1.6 to 3.1 for ages 25 to 29, vs. ages 30 to 39 years), who identified as transgender women (aHR 2.0, 95% CI 1.2 to 3.4, vs. cisgender men), and who had mental health disorders (aHR 1.2, 95% CI 1.1 to 1.4 for each additional disorder) were more likely to have discontinuations.ConclusionsDiscontinuations of PrEP use among this American sample of predominately MSM were common, particularly among patients who were younger, identified as transgender women, or had behavioural health issues. As HIV seroconversions occurred after discontinuations of PrEP, strategies to prevent inappropriate discontinuations are needed.

AbstractIntroductionDespite healthcare providers' growing awareness of pre‐exposure prophylaxis (PrEP), prescription rates remain low. PrEP is an efficacious HIV prevention strategy recommended for use with condoms but still protective in their absence. Concern about the impact of PrEP on condom use and other risk behaviour is, nonetheless, among the barriers to prescription commonly reported. To understand the implications of this concern for PrEP access, we examined how medical students' willingness to prescribe PrEP varied by patients' condom use and partnering practices. We also assessed the perceived acceptability of various reasons for condom discontinuation with PrEP.MethodsAn online survey was distributed to 854 medical students in the Northeastern US in 2015. Participants (n = 111) were surveyed about their willingness to prescribe PrEP for each of six male patients who systematically differed in their reported condom use (sustained use, sustained nonuse, or discontinuation with PrEP) and partnering practices (single male partner with untreated HIV or multiple male partners of unknown HIV status). Participants also reported perceived acceptability of four reasons for condom discontinuation: pleasure, sexual functioning, intimacy, and conception.ResultsWillingness to prescribe PrEP was inconsistent with patient risk: When the patient used condoms and planned to sustain condom use, most participants were willing to prescribe PrEP – 93% if the patient had a single partner and 86% if the patient had multiple partners. Fewer were willing to prescribe if the patient did not use condoms and planned to sustain nonuse (53% and 45%, respectively) or used condoms but planned to discontinue use (27% and 28%). Significantly fewer participants were willing to prescribe for a patient with multiple partners versus a single partner when the patient reported sustained condom use or sustained condom nonuse. The number of participants who were willing to prescribe was similarly low for a patient with multiple partners versus a single partner when the patient reported that he planned to discontinue condom use. More participants accepted a patient discontinuing condoms for conception (69%) than for intimacy (23%), pleasure (14%), or sexual functioning (13%).ConclusionMedical students' clinical judgments were misaligned with patient risk and suggest misconceptions or personal values may undermine provision of optimal HIV prevention services.