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The HIV preexposure prophylaxis optimization intervention (PrEP-OI) study evaluated the efficacy of a panel management intervention using PrEP coordinators and a web-based panel management tool to support healthcare providers in optimizing PrEP prescription and ongoing PrEP care.The PrEP-OI study was a stepped-wedge randomized clinical trial conducted across 10 San Francisco Department of Public Health primary care sites between November 2018 and September 2019. Each month, clinics one-by-one initiated PrEP-OI in random order until all sites received the intervention by the study team.The primary outcome was the number of PrEP prescriptions per month. Secondary outcomes compared pre- and postintervention periods on whether PrEP was discussed and whether PrEP-related counseling (e.g., HIV risk assessment, risk reduction counseling, PrEP initiation/continuation assessment) was conducted. Prescription and clinical data were abstracted from the electronic health records. We calculated incidence rate ratios (IRR) and risk ratios (RR) to estimate the intervention effect on primary and secondary outcomes.The number of PrEP prescriptions across clinics increased from 1.85/month (standard deviation [SD] = 2.55) preintervention to 2.44/month (SD = 3.44) postintervention (IRR = 1.34; 95% confidence interval [CI] = 1.05-1.73; P = 0.021). PrEP-related discussions during clinic visits (RR = 1.13; 95% CI = 1.04-1.22; P = 0.004), HIV risk assessment (RR = 1.40; 95% CI = 1.14-1.72; P = 0.001), and risk reduction counseling (RR = 1.16; 95% CI = 1.03-1.30; P = 0.011) increased from the pre- to the postintervention period. Assessment of PrEP initiation/continuation increased over time during the postintervention period (RR = 1.05; 95% CI = 0.99-1.11; P = 0.100).A panel management intervention using PrEP coordinators and a web-based panel management tool increased PrEP prescribing and improved PrEP-related counseling in safety-net primary care clinics.

BackgroundKey components of Ending the HIV Epidemic (EHE) plan include increasing HIV antiretroviral therapy (ART) and HIV preexposure prophylaxis (PrEP) coverage. One complication to addressing this service delivery challenge is the wide heterogeneity of HIV burden and healthcare access across the U.S. It is unclear how the effectiveness and efficiency of expanded PrEP will depend on different baseline ART coverage.MethodsWe used a network-based model of HIV transmission for men who have sex with men (MSM) in San Francisco. Model scenarios increased varying levels of PrEP coverage relative under current empirical levels of baseline ART coverage and two counterfactual levels. We assessed the effectiveness of PrEP with the cumulative percent of infections averted (PIA) over the next decade and efficiency with the number needed to treat (NNT) by PrEP required to avert one HIV infection.ResultsIn our projections, only the highest levels of combined PrEP and ART coverage achieved the EHE goals. Increasing PrEP coverage up to 75% showed that PrEP effectiveness was higher at higher baseline ART coverage with the PIA ranging from 61% in the lowest baseline ART coverage population to 75% in the highest ART coverage. The efficiency declined with increasing ART (NNT range from 41 to 113).ConclusionsImproving both PrEP and ART coverage would have a synergistic impact on HIV prevention even in a high baseline coverage city like San Francisco. Efforts should focus on narrowing the implementation gaps to achieve higher levels of PrEP retention and ART sustained viral suppression.

Based on the results of the IPERGAY study, on-demand HIV pre-exposure prophylaxis (PrEP; also known as “non-daily PrEP,” “event-driven PrEP,” or “2-1-1 PrEP”) is being requested more frequently by patients who have intermittent sexual risk or are unable/unwilling to take daily PrEP; therefore, clinicians will be increasingly required to familiarize themselves with its appropriate use. In this perspective, we summarize data related to on-demand PrEP, describe advantages and disadvantages for this alternative dosing strategy, and provide clinical counseling points.

Objective:Dissemination of pre-Exposure Prophylaxis (PrEP) is a priority for reducing new HIV infections, especially among vulnerable populations. However, there are limited data available on PrEP discontinuation following initiation, an important component of the PrEP cascade.Design:Patients receiv

BackgroundSafe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection.MethodsWe conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection.ResultsThe intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified.ConclusionsCAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).

Background Young men who have sex with men (YMSM) are disproportionately impacted by HIV and other sexually transmitted infections (STIs) in the United States (US) and have low rates of HIV/STI testing. Provision of HIV self-testing and STI self-collection can increase testing rates, and access to these kits through mobile applications (apps) could help facilitate YMSM using HIV self-testing and STI self-collection. Methods Data for this study comes from two pilot randomized controlled trials (RCTs) of mobile apps within the Adolescent Trials Network-LYNX and MyChoices-aimed to increase HIV/STI testing among YMSM (age 15-24) who had not recently tested for HIV and were at high risk for HIV acquisition across five US cities. Both apps include the ability to order a HIV self-test with rapid results and a kit for STI self-collection and mailing of samples for syphilis, gonorrhea and chlamydia to a lab for testing. Using assessments of app users (n=80) at pre-randomization and at 3- and 6-months post-randomization and online interview data from a purposive sample of app users (n=37), we report on experiences and lessons learned with HIV self-testing and STI self-collection kits ordered via the apps. Results Participants were on average 20.7 years of age (SD =2.4), and 49% were non-White or multiple race/ethnicity. Sixty-three percent had a prior HIV test. Over half (58%) had a prior STI test, but only 3% had tested within the past 3 months. Nearly two-thirds ordered an HIV self-testing kit; of whom, 75% reported using at least one self-test kit over the study period. STI self-collection kit ordering rates were also high (54%); however, STI self-collection kit return rates were lower (13%), but with a high positivity rate (5.3%). Both HIV self-testing and STI self-collection kits were highly acceptable, and 87% reported that it was extremely/very helpful to be able to order these kits through the apps. The most common reason for not ordering the HIV/STI kits was preferring to test at a clinic. In interviews, participants expressed feeling empowered by being able to test at home; however, they also raised concerns around STI sample collection. Conclusions HIV self-testing and STI self-collection kit ordering via mobile apps is feasible, acceptable and may show promise in increasing testing rates among YMSM. The LYNX and MyChoices apps are currently being tested in a full-scale efficacy trial, and if successful, these innovative mobile apps could be scaled up to efficiently increase HIV/STI testing among youth across the US.

Mobile app health research presents myriad opportunities to improve health, and simultaneously introduces a new set of challenges that are non-intuitive and extend beyond typical training received by researchers. Informed by our experiences with app development for health research, we discuss some of the most salient pitfalls when working with emerging technology as well as potential strategies to avoid or resolve these challenges. To address challenges at the project level, we suggest strategies that researchers can use to future-proof their research, such as using theory and involving those with app development expertise as part of a research team. At the structural level, we include a new model to characterize the relationship between technology- and research-timelines, and provide ideas regarding how to best address this challenge. Given that screen-based time now predominates our lived experiences, it is important that health researchers have the capacity and structural support to develop interventions that utilize these technologies, assess them rigorously, and ensure their timely and equitable dissemination.

PrEP persistence, or PrEP use over time, has been shown to be short, with most PrEP users stopping within 6–12 months. Furthermore, those most vulnerable to HIV often use PrEP for shorter periods. This qualitative study explores patient, provider, and contextual factors that influence PrEP persistence. In interviews with 25 PrEP users and 18 PrEP providers in San Francisco’s safety net clinics, we analyze the perceived benefits and difficulties of taking PrEP, including structural barriers. We identify different steps in receipt of PrEP care (clinic visits and lab tests, pharmacy interactions, and medication adherence), and describe barriers and facilitators for providers and patients at each step. Our findings suggest that drop-in visits, streamlined testing, standing orders for labs, and 90-day PrEP prescriptions are highly desirable for many PrEP users. Also important are the proactive provision of adherence support and counseling, and referrals for housing, substance use, and mental health services.

IntroductionPre-exposure prophylaxis (PrEP) has demonstrated to be a highly effective method for preventing HIV; however, many individuals with PrEP indications are not receiving PrEP. Primary care settings provide an opportunity to offer PrEP to a wide range of patients. In this paper, we describe the PrEP Optimisation Intervention (PrEP-OI), which includes a PrEP Coordinator and a web-based panel management tool (called PrEP-Rx), and is targeted at healthcare providers (HCPs) to increase PrEP uptake and persistence among those at risk for acquiring HIV.Methods and analysisThe PrEP-OI study evaluates the efficacy of the PrEP intervention (PrEP Coordinator + PrEP-Rx) to increase PrEP prescriptions through a stepped-wedge design among 10 primary care clinical sites in the San Francisco Department of Public Health. The number of PrEP initiation prescriptions constitute the primary outcome, and we hypothesise that the mean number of PrEP prescriptions written will significantly increase after the clinics initiate PrEP-OI versus before this intervention. Secondary objectives include: 1-differences in PrEP initiation, duration of use and reasons for discontinuation based on patient’s age, race/ethnicity and sex/gender, and by clinic and HCP characteristics, 2-sustainability of the intervention during a 12-month follow-up after the stepped-wedge phase, and 3-facilitators and barriers of PrEP delivery and experiences with the proposed PrEP intervention through qualitative interviews with HCPs. The results of this study can provide valuable insight into methods to reduce the burden of PrEP care on HCPs and improve PrEP continuum of care.Ethics and disseminationThis study and its protocols have been approved by the University of California, San Francisco (UCSF) Institutional Review Board. Study staff will disseminate findings locally (eg, the UCSF Centre for AIDS Prevention Studies’ Community Engagement Core), statewide (eg, the California Department of Public Health’s Office of AIDS) and nationally and internationally at conferences related to HIV.Trial registration numberNCT03532191.

Pre-exposure prophylaxis (PrEP) is highly effective, although PrEP adherence and persistence has been variable during real world implementation. Little is known about missed opportunities to enhance PrEP adherence among individuals who later HIV seroconverted after using PrEP. The goal of this analysis was to identify all HIV infections among individuals who had accessed PrEP in an integrated health system in San Francisco, and to identify potentially intervenable factors that could have prevented HIV infection through in-depth interviews with people who HIV seroconverted after using PrEP.We identified individuals who initiated PrEP in an integrated safety-net public health system and performed in-depth chart review to determine person-time on and after stopping PrEP over six years. We identified all PrEP seroconversions using the Centers for Disease Control and Prevention's Enhanced HIV/AIDS Reporting System and then calculated HIV incidence while using PrEP and during gaps in use. We then performed in-depth interviews with those who seroconverted.Overall, 986 initiated PrEP across the San Francisco Department of Public Health from July 2012 to November 2018. Data were gathered from 895 person-years on PrEP and 953 after stopping PrEP. The HIV incidence was 7.5-fold higher after stopping PrEP compared to while on PrEP (95% CI 1 to 336). Of the eight individuals who HIV seroconverted; only one was taking PrEP at the time of seroconversion but was using on-demand PrEP inconsistently. All eight agreed to qualitative interviews. Major barriers to PrEP persistence included substance use, mental health and housing loss; difficulty accessing PrEP due to cost, insurance, and the cost and time of medical visits; difficulty weighing PrEP's benefit versus self-perceived risk; and entering a primary partnership. The individual who developed HIV using on-demand PrEP reported confusion about the dosing regimen and which sexual encounters required accompanying PrEP dosing.HIV incidence during gaps in PrEP use was nearly eight-fold higher than while on PrEP in this large cohort in San Francisco. Many individuals who stop PrEP remain at risk of HIV, and participants reported that proactive outreach could potentially have prevented HIV infections. Individuals using non-daily PrEP may require additional education and support in the United States.

Introduction Pre‐exposure prophylaxis (PrEP) is highly effective, although PrEP adherence and persistence has been variable during real world implementation. Little is known about missed opportunities to enhance PrEP adherence among individuals who later HIV seroconverted after using PrEP. The goal of this analysis was to identify all HIV infections among individuals who had accessed PrEP in an integrated health system in San Francisco, and to identify potentially intervenable factors that could have prevented HIV infection through in‐depth interviews with people who HIV seroconverted after using PrEP. Methods We identified individuals who initiated PrEP in an integrated safety‐net public health system and performed in‐depth chart review to determine person‐time on and after stopping PrEP over six years. We identified all PrEP seroconversions using the Centers for Disease Control and Prevention’s Enhanced HIV/AIDS Reporting System and then calculated HIV incidence while using PrEP and during gaps in use. We then performed in‐depth interviews with those who seroconverted. Results Overall, 986 initiated PrEP across the San Francisco Department of Public Health from July 2012 to November 2018. Data were gathered from 895 person‐years on PrEP and 953 after stopping PrEP. The HIV incidence was 7.5‐fold higher after stopping PrEP compared to while on PrEP (95% CI 1 to 336). Of the eight individuals who HIV seroconverted; only one was taking PrEP at the time of seroconversion but was using on‐demand PrEP inconsistently. All eight agreed to qualitative interviews. Major barriers to PrEP persistence included substance use, mental health and housing loss; difficulty accessing PrEP due to cost, insurance, and the cost and time of medical visits; difficulty weighing PrEP’s benefit versus self‐perceived risk; and entering a primary partnership. The individual who developed HIV using on‐demand PrEP reported confusion about the dosing regimen and which sexual encounters required accompanying PrEP dosing. Conclusions HIV incidence during gaps in PrEP use was nearly eight‐fold higher than while on PrEP in this large cohort in San Francisco. Many individuals who stop PrEP remain at risk of HIV, and participants reported that proactive outreach could potentially have prevented HIV infections. Individuals using non‐daily PrEP may require additional education and support in the United States.

Current strategies to prevent sexually transmitted infections (STIs) are not controlling the epidemic. The efficacy of doxycycline STI postexposure prophylaxis shows promise in pilot studies, but wider acceptability is unknown. A majority (84%) of diverse individuals using a gay social networking application were interested in doxycycline STI postexposure prophylaxis. Doxycycline STI postexposure prophylaxis should be examined in larger trials.

BACKGROUND Despite continued reductions in the number of HIV cases reported among San Francisco men who have sex with men (MSM) and the HIV-prevention potential offered by pharmaceutical tools such as pre-exposure prophylaxis (PrEP), there are uncertainties, particularly given reported decreases in consistent condom use. A key uncertainty is what groups of MSM should be targeted. This study estimates the distribution of behavioral patterns before infection among San Francisco MSM newly infected with HIV in 2014. METHODS We used a novel modeling approach. The approach uses estimates from the National HIV Behavioral Surveillance System for MSM, the Medical Monitoring Project, 2 trials of PrEP, and a meta-analysis of per-act risks of HIV infection. RESULTS The modeling study suggests that 76% of newly HIV-infected MSM in 2014 were individuals with no discernible strategy in the 6 months before infection: that is, they had condomless receptive anal intercourse with one or more partners not perceived to be HIV uninfected. An estimated 7% of newly infected MSM were serosorters before infection. CONCLUSIONS Prevention efforts in San Francisco must reach HIV-uninfected MSM with no discernible behavioral strategy, a group that constitutes 8% of HIV-uninfected MSM in the city. Our study suggests that if all HIV-uninfected, San Francisco MSM with no discernible strategy had been on PrEP in 2014, there would have been 70% fewer HIV infections among San Francisco MSM. Uncertainty analysis suggests that PrEP's impact may be maximized by encouraging PrEP persistence and concomitant reductions in sexual risk behaviors.

Resistance to reverse transcriptase and protease inhibitors was frequently detected in HIV from black men who have sex with men (MSM) enrolled in the HIV prevention trials network (HPTN) 061 study. In this study, integrase strand transfer inhibitor (INSTI) resistance was analyzed in black MSM enrolled in HPTN 061 (134 infected at enrollment and 23 seroconverters) and a follow-up study, HPTN 073 (eight seroconverters). The ViroSeq HIV-1 Integrase Genotyping Kit (Abbott Molecular) was used for analysis. Major INSTI resistance mutations were not detected in any of the samples. HIV from 14 (8.4%) of the 165 men, including 4 (12.9%) of 31 seroconverters, had accessory or polymorphic INSTI-associated mutations. The most frequently detected mutation was E157Q. These findings are promising because INSTI-based regimens are now recommended for first-line antiretroviral treatment and because long-acting cabotegravir is being evaluated for pre-exposure prophylaxis.

Lack of healthcare provider knowledge, capacity, and willingness to prescribe PrEP are barriers to PrEP delivery in clinical settings. We implemented the PrEP Optimization Intervention (PrEP-OI) combining a PrEP Coordinator with an online panel management tool to assist providers with PrEP uptake, persistence, and management in 12 San Francisco Department of Public Health Primary Care Clinics. Medical directors (N = 10) identified important factors to consider prior to implementation, including shortage of clinical space for coordinators, medical mistrust, language barriers, and limited lab hours, along with the need for education of providers and staff and patient outreach. Among 110 providers who completed a baseline survey, the majority had reservations in asking about sexual practices and having conversations about PrEP. Providers reported PrEP-OI increased their efficiency and capacity to manage PrEP patients, and served as a gateway to additional services. These results highlight the promise of a provider-based intervention to improve the PrEP continuum and maximize the impact of PrEP.

Accurate HIV risk assessment among men who have sex with men (MSM) is important to help providers assess risk, and target HIV prevention interventions. We sought to develop an evidence-based HIV risk assessment tool for US MSM that is inclusive of Black MSM. Data from four large longitudinal cohorts of MSM were used to develop (EXPLORE), and validate (VAX004, HPTN061, and HVTN505). These data included visits in which participants self-reported HIV risk behavior and underwent HIV testing. We developed a pooled logistic model for incident HIV infection based on self-reported risk behaviors during the 6months before each study visit. A total of 4069 MSM were used for the development cohort, and 8047 MSM in the three validation cohorts through 2013. The final model includes age (

BACKGROUND HIV disproportionately impacts transgender populations globally, creating challenges to inclusion in trials requiring low HIV risk profiles (LHRP) for acquisition. Our knowledge of transgender individuals with LHRP is limited. We conducted an analysis of transgender and cisgender individuals in HVTN trials enrolling individuals with LHRP. METHODS We analyzed data from 694 participants enrolled in the phase 1-2a HVTN trials in the US and Peru from 2009 to 2014 that included individuals who reported gender identity (GI) differing from assigned birth sex (transgender [TG]), and compared them with those who reported a congruent GI (cisgender [CG]). RESULTS 681 participants (98%) were CG and 13 (2%) were TG. Mean age was 25 years. 16% were Hispanic and most (69%) were White. Reasons for enrolling included to help find an effective vaccine (TG 100%; CG 98%) and help their community (TG 100%; CG 96%). Significant differences by GI were observed in reported pre-existing conditions (p = 0.004); however, approximately 10% of pre-existing conditions reported by TG were GI-related (e.g., gender dysphoria). Significant differences were observed in hormone therapy use (p

Objective adherence metrics for tenofovir (TFV) disoproxil fumarate/emtricitabine (FTC)-based pre-exposure prophylaxis (PrEP) were critical for interpretation of efficacy in PrEP clinical trials, and there is increasing interest in using drug levels to tailor interventions for reengagement and adherence. Point-of-care immunoassays for TFV, which examine short-term adherence, are in development. However, the ability of poor short-term and long-term adherence to predict future PrEP nonretention is unknown.Secondary data analysis of a large, prospective multi-site U.S. PrEP demonstration project.An adjusted Cox-proportional hazards model examined the relationship of dried blood spot (DBS) levels of FTC-triphosphate (FTC-TP) or TFV-diphosphate (TFV-DP), measures of short-term and long-term PrEP adherence, respectively, with future study nonretention.Overall, 294 individuals (median age 33 years) contributed drug levels within the U.S. PrEP demonstration project. By the end of study, 27% were lost to follow-up, 25% had at least one undetectable FTC-TP level indicating poor short-term adherence, and 29% had a drug level indicating suboptimal long-term adherence (TFV-DP700 fmol/punch). The strongest factor associated with future study nonretention using a binary drug-level cut-off was an undetectable DBS FTC-TP level (adjusted hazard ratio 6.3; 95% confidence interval 3.8 to 10.2). The suboptimal long-term adherence based on low DBS TFV-DP levels was also associated with nonretention (adjusted hazard ratio 4.3; 95% confidence interval: 2.4 to 7.6).Both short- and long-term metrics of PrEP adherence are strongly associated with future loss to follow-up in a U.S. demonstration project study. Short-term metrics of adherence, once available at the point-of-care, could be used to direct real-time tailored retention and adherence interventions.

Background Youth participating in mobile health (mHealth) intervention trials often engage with the technologies [e.g., applications (app) or mobile-optimized websites] only partially, often prematurely discontinuing use altogether. Limited engagement can impact the interventions effect on behavior change and compromise researchers' ability to test and estimate the true efficacy of their interventions. While mHealth interventions have been shown to be feasible and acceptable to youth, across diverse health conditions, strategies to increase engagement have been less well studied. Specifically, within HIV prevention and care mHealth interventions, there is not consensus as to which components represent the "key ingredients" to support maximal engagement of youth. Further, successful intervention evaluation requires the ability to systematically track users' engagement with intervention components (i.e., paradata) to evaluate its effects on behavior change. Methods As part of the Adolescent Medicine Trials Network UNC/Emory Center for Innovative Technology (iTech) portfolio of HIV/AIDS Interventions, we present diverse strategies used across five mHealth protocols seeking to promote youth engagement, track and measure engagement through paradata, and incorporate these components into mHealth intervention evaluations. Results We describe the importance of defining and measuring engagement using case studies from iTech to illustrate how different research teams select mHealth features to promote youth engagement over time, taking into account features embedded in the technology design, key mechanisms of change and trial outcomes (e.g., HIV testing, pre-exposure prophylaxis uptake and adherence, HIV treatment adherence). Finally, we discuss how the research teams plan to evaluate engagement's role on their intervention's outcomes. Conclusions Based on this synthesis, we discuss strategies to enhance mHealth engagement during intervention development and design, ensure its monitoring and reporting throughout the trial, and evaluate its impact on trial outcomes.

Depression is linked to a range of poor HIV-related health outcomes. Minorities and men who have sex with men (MSM), suffer from high rates of depression. The current study examined the relationship between depressive symptoms and social network characteristics among community-recruited Black MSM in HPTN 061 from 6 US cities. A social network inventory was administer at baseline and depression was assessed with the CES-D at baseline, 6, and 12-months. At baseline, which included 1167 HIV negative and 348 HIV positive participants, size of emotional, financial, and medical support networks were significantly associated with fewer depressive symptoms. In longitudinal mixed models, size of emotional, financial, and medical support networks were significantly associated with fewer depressive symptoms as was the number of network members seen weekly. In the multivariate analyses, size of medical appointment network remained statistically significant (aOR= 0.89, CI=0.81-0.98). These findings highlight the importance of network support of medical care on depression and suggest the value of support mobilization.

Increasing the diversity of the HIV research workforce remains a priority for research and funding organizations in the US. Mentorship is a vital component for early-career investigators, especially for underrepresented racial/ethnic and sexual minority HIV investigators. These investigators face unique social and structural challenges to developing and fostering mentorship relationships, as well as building a solid foundation for a successful career in HIV research. This article provides a perspective from four Black early-career investigators, supplemented with comments from 15 underrepresented investigators in the US, as they reflect on their needs, challenges, contributions, and successes in finding the right mentor and mentorship environment, balancing the opportunities for, and "threats" to success, as well as providing mentorship to other underrepresented and aspiring HIV investigators. Mentorship programs must address these needs and challenges while building on the strengths of underrepresented HIV investigators in order to improve recruitment, retention and ultimately the pipeline of these researchers.

To evaluate factors associated with HIV tropism among Black men who have sex with men (MSM) in the United States enrolled in a clinical study (HIV Prevention Trials Network 061).HIV tropism was analyzed using a phenotypic assay (Trofile assay, Monogram Biosciences). Samples were analyzed from 43 men who were HIV infected at enrollment and reported either exclusive insertive intercourse or exclusive receptive intercourse; samples were also analyzed from 20 men who were HIV uninfected at enrollment and seroconverted during the study. Clonal analysis of individual viral variants was performed for seroconverters who had dual/mixed (DM) viruses.DM viruses were detected in samples from 11 (26%) of the 43 HIV-infected men analyzed at the enrollment visit; HIV tropism did not differ between those reporting exclusive insertive vs receptive intercourse. DM viruses were also detected in five (25%) of the 20 seroconverters. DM viruses were associated with lower CD4 cell counts. Seroconverters with DM viruses had dual-tropic viruses only or mixed populations of CCR5- and dual-tropic viruses.DM viruses were frequently detected among Black MSM in this study, including seroconverters. Further studies are needed to understand factors driving transmission and selection of CXCR4- and dual-tropic viruses among Black MSM.

Background Maintaining retention in preexposure prophylaxis (PrEP) care among diverse patient populations will be needed to support PrEP’s efficacy. We characterized patterns of PrEP care retention in a US municipal primary care health network and examined whether missed visits, a metric of care retention that is easy to evaluate in clinic, are associated with subsequent discontinuation. Methods We included individuals on PrEP from July 2012 until August 2017 in the San Francisco Primary Care Clinics, a 15-clinic municipal health network. We categorized PrEP usage patterns as follows: early discontinuation (, Preexposure prophylaxis (PrEP) users in primary care continued PrEP for a median of 8 months. Transgender women experienced higher risk of early discontinuation; younger users experienced late discontinuation. Missed visits during PrEP are associated with discontinuation and should trigger outreach.

Background Timely pre-exposure prophylaxis (PrEP) initiation is critical in at-risk populations, given that HIV acquisition risk persists during delays. Time to treatment initiation, a key metric in HIV care, has not been explored among PrEP users. Interventions that reduce time to PrEP initiation could prevent HIV infections. Setting Individuals initiating PrEP in a large primary care health network of 15 clinics, the San Francisco Primary Care Clinics (SFPCC), from July 2012 to July 2017 (N = 411). Methods We examined factors associated with time from first PrEP discussion with a provider to PrEP initiation date using an adjusted Cox proportional-hazards model, with hazard ratios (HRs) >1 indicating earlier initiation. We also examined the relationship between delayed PrEP initiation and PrEP persistence (staying on PrEP) in an adjusted Cox proportional-hazards model. Results PrEP users initiated PrEP after a median of only 7 days. However, there were notable outliers, with 29% waiting >30 days and 12% waiting >90 days. In an adjusted proportional-hazards model, a panel management and patient navigation intervention was associated with earlier PrEP initiation [HR: 1.5; 95% confidence interval (CI): 1.1 to 2.0], whereas only other race/ethnicity compared with white race was associated with delayed PrEP initiation (HR: 0.7; 95% CI: 0.5 to 1.0). Delayed PrEP initiation >30 days was associated with shorter PrEP persistence in an adjusted proportional-hazards model (HR: 1.3; 95% CI: 1.0 to 1.7). Conclusions PrEP initiation within a week is feasible in a primary care safety-net health system. Setting a goal of rapid PrEP initiation, with the support of panel management and patient navigation, could address delays in at-risk groups.

Summary Background Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly protective against HIV infection. We report a case of tenofovir-susceptible, emtricitabine-resistant HIV acquisition despite high adherence to daily PrEP. Methods Adherence to PrEP was assessed by measuring concentrations of emtricitabine and tenofovir disoproxil fumarate or their metabolites in plasma, dried blood spots, and hair. After seroconversion, genotypic and phenotypic resistance of the acquired virus was determined by standard clinical tests and by single-genome sequencing of proviral genomes. HIV partner services identified the likely transmission partner. Findings A 21-year-old Latino man tested positive for HIV infection 13 months after PrEP initiation. He had a negative HIV antibody test, but detectable HIV RNA with 559 copies per mL. He reported good adherence to daily PrEP. He was linked to care and immediately started antiretroviral therapy, at which point his RNA was 1544 copies per mL and his HIV antibody test was positive. The HIV genotype revealed Met184Val, Leu74Val, Leu100Ile, and Lys103Asn mutations in reverse transcriptase, and the phenotype showed susceptibility to tenofovir disoproxil fumarate and resistance to emtricitabine. Segmental hair analysis of tenofovir disoproxil fumarate concentrations measured in 1 cm segments of hair from the scalp indicated consistently high adherence to PrEP in each of the 6 months before HIV diagnosis (0·0672–0·0889 ng/mg). Concentrations of tenofovir diphosphate (1012 fmol per punch) and emtricitabine triphosphate (0·266 fmol per punch) in a dried blood spot indicated high adherence over the preceding 6 weeks. Concentrations of emtricitabine (870·5 ng/mL) and tenofovir disoproxil fumarate (188·2 ng/mL) measured in plasma 3 months before HIV seroconversion confirmed adherence in the days preceding that visit. The likely transmission partner was not engaged in HIV primary care and had a similar viral genotype. Interpretation Acquisition of HIV virus that is susceptible to tenofovir disoproxil fumarate, but resistant to emtricitabine can occur despite high adherence to PrEP. Quarterly screening for HIV and sexually transmitted diseases facilitates early diagnosis in people on PrEP; when combined with prompt linkage to care and partner services this can prevent onward transmission of HIV. Funding US National Institutes of Health.

Men who have sex with men (MSM) continue to be disproportionately impacted globally by the HIV epidemic. Studies suggest that HIV self-testing (HIVST) is highly acceptable among MSM. Social network strategies to increase testing are effective in reaching MSM, particularly MSM of color, who may not otherwise test. We tested a social network-based strategy to distribute HIVST kits to African American MSM (AAMSM) and Latino MSM (LMSM).This study was conducted in Alameda County, California, a large, urban/suburban county with an HIV epidemic mirroring the national HIV epidemic.From January 2016 to March 2017, 30 AAMSM, LMSM, and transgender women were trained as peer recruiters and asked to distribute 5 self-test kits to MSM social network members and support those who test positive in linking to care. Testers completed an online survey after their test. We compared peer-distributed HIVST testing outcomes to outcomes from Alameda County's targeted, community-based HIV testing programs using χ tests.Peer-distributed HIVST to 143 social and sexual network members, of whom 110 completed the online survey. Compared with MSM who used the County's sponsored testing programs, individuals reached through the peer-based self-testing strategy were significantly more likely to have never tested for HIV (3.51% vs. 0.41%, P0.01) and to report a positive test result (6.14% vs. 1.49%, P0.01).Findings suggest that a network-based strategy for self-test distribution is a promising intervention to increase testing uptake and reduce undiagnosed infections among AAMSM and LMSM.

Insufficient pre-exposure prophylaxis (PrEP) laboratory monitoring could increase HIV resistance and sexually transmitted infections. We examined test-ordering in a primary care network. Providers did not order HIV testing before almost one-quarter of PrEP initiations; panel management was associated with higher testing. Effective monitoring is needed to maximize PrEP’s preventive impact.

Background: Young men who have sex with men (YMSM) in the United States have among the highest incidence of HIV and sexually transmitted infection (STI) and the lowest uptake of HIV and STI testing and pre-exposure prophylaxis (PrEP). Nearly universal mobile phone ownership among youth provides an opportunity to leverage mobile health apps to increase HIV/STI testing and PrEP uptake among YMSM. Objective: The goals of this project are to develop and refine LYNX, a novel mobile app to support linkage to HIV/STIs testing and PrEP services among YMSM in the United States, and to evaluate the acceptability and feasibility of LYNX in a pilot randomized controlled trial (RCT). Methods: This research protocol will be conducted in 3 phases: an iterative development phase with a series of 3 focus groups among 20 YMSM to refine the LYNX app; an open technical pilot among 15 YMSM to optimize usability of the app; and then a 6-month pilot RCT among 60 HIV-uninfected YMSM at risk for HIV acquisition. Developed using the Information, Motivation, and Behavioral skills theoretical model, the LYNX app includes an electronic diary to track sexual behaviors (information), a personalized risk score to promote accurate risk perception (information/motivation), testing reminders (motivation/behavioral skills), and access to home-based HIV/STI testing options and geospatial-based HIV/STI testing care sites (behavioral skills). Feasibility and acceptability will be assessed through app analytics of usage patterns and acceptability scales administered via computer-assisted self-interview at 3 and 6 months. We will also evaluate preliminary efficacy by comparing the proportion of YMSM who test at least once during the 6-month pilot and the proportion who successfully link to a PrEP provider in the intervention versus control groups. Results: Formative work is currently underway. The LYNX pilot RCT will begin enrollment in October 2018, with study results available in 2019. Conclusions: The LYNX app is one of the first mobile apps designed to increase HIV/STI testing and PrEP uptake among YMSM. As low-perceived risk is a barrier to HIV/STI testing and PrEP use among youth, the personalized risk assessment and interactive sexual diary in LYNX could assist YMSM in better understanding their HIV risk and providing motivation to test for HIV/STIs and initiate PrEP. Coupled with community-based recruitment, this novel mobile app has great potential to reach and engage YMSM not currently involved in care and increase rates of HIV/STI testing and PrEP uptake in this vulnerable population. Trial Registration: ClinicalTrials.gov NCT03177512; https://clinicaltrials.gov/ct2/show/NCT03177512 (Archived by WebCite at http://www.webcitation.org/73c917wAw) International Registered Report Identifier (IRRID): DERR1-10.2196/10659

Background: Pre-exposure prophylaxis (PrEP) has been shown to be highly effective for the prevention of HIV in clinical trials and demonstration projects, but PrEP uptake and adherence outside of these settings in the United States has been limited. Lack of knowledge and willingness of health care providers (HCPs) to prescribe PrEP is an important barrier to implementation. Objective: The objective of this study was to describe and examine the feasibility and acceptability of a PrEP Optimization Intervention (PrEP-OI) targeted at HCPs. The ultimate purpose of this intervention was to increase PrEP uptake, adherence, and persistence among those at risk for HIV acquisition. Methods: This intervention included the following: (1) a Web-based panel management tool called PrEP-Rx, which provides comprehensive HIV risk assessment, automates reminders for follow-up, and reports patients’ history of PrEP use; and (2) centralized PrEP coordination by a clinical support staff member (ie, the PrEP coordinator) who can identify individuals at risk for HIV, provide medical insurance navigation, and support multiple HCPs. Feasibility was evaluated based on HCPs’ ability to log in to PrEP-Rx and use it as needed. Acceptability was assessed via individual formative qualitative interviews with HCPs after 1 month of the intervention. Results: The intervention was feasible and acceptable among HCPs (N=6). HCPs identified system-level barriers to PrEP provision, many of which can be addressed by this intervention. HCPs noted that the intervention improved their PrEP knowledge; increased ease of PrEP prescription; and was likely to improve patient engagement and retention in care, enhance communication with patients, and improve patient monitoring and follow-up. Conclusions: Given the critical role HCPs serve in disseminating PrEP, we created an easy-to-use PrEP optimization intervention deemed feasible and acceptable to providers. Further research on this tool and its ability to impact the PrEP continuum of care is needed.

Purpose HIV disproportionately affects young men who have sex with men. Pre-exposure prophylaxis (PrEP) can prevent HIV acquisition; however, youth access to PrEP is limited by provider willingness to prescribe PrEP. Methods We conducted an online survey of clinicians working with adolescents (aged 13–17 years) and young adults (aged 18–26 years) in the United States through the Society of Adolescent Health and Medicine. We used multivariate logistic regression to assess provider beliefs associated with willingness to provide PrEP. Results Nearly all (93.2%) providers had heard of PrEP, and 57 (35.2%) had prescribed PrEP. While almost all providers (95%) agreed that PrEP prevents HIV, fewer were willing to prescribe to young adults (77.8%) or adolescents (64.8%). Willingness to prescribe PrEP was strongly associated with the belief that providers had enough knowledge to safely provide PrEP to adolescents (OR 2.11, confidence interval [CI]: 1.18–3.76, p = .01) and young adults (odds ratio 5.19, CI: 2.15–12.50, p ≤ .001), and that adolescents would be adherent (odds ratio 3, CI: 1.30–6.90, p = .01). Response rate was 17%. Conclusions Almost all providers had heard of PrEP and most providers were willing to prescribe PrEP. Provider education and tools to promote provider self-efficacy and adolescent adherence might improve provider willingness to provide PrEP.

Little is known about HIV treatment optimism and risk behaviors among Black men who have sex with men (BMSM). Using longitudinal data from BMSM in the HPTN 061 study, we examined participants’ self-reported comfort with having condomless sex due to optimistic beliefs regarding HIV treatment. We assessed correlates of treatment optimism and its association with subsequent risk behaviors for HIV acquisition or transmission using multivariable logistic regression with generalized estimating equations. Independent correlates of treatment optimism included age ≥35 years, annual household income

Background Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (TFV) disoproxil fumarate (FTC/TDF) is highly protective against HIV infection. We report the second case of acquisition of TDF-susceptible HIV despite high adherence to PrEP, confirmed by drug level testing. Methods PrEP adherence was assessed by measuring FTC/TDF metabolites in dried blood spots (DBS) and FTC/TFV concentrations in segments of scalp hair. Genotypic and phenotypic resistance were evaluated. HIV partner services (PS) and HIV sequences reported to HIV surveillance with a genetic distance ≤1.5% (by HIV-Trace) identified likely transmission partners. Results A 21-year-old Latino man presented 13 months after PrEP initiation. He was HIV negative by rapid HIV antibody (Ab) and HIV RNA pooling (detection limit ~40 copies/mL) at PrEP initiation and at months 3, 6, and 10. At the 13-month visit, he was asymptomatic and his rapid HIV Ab was negative. Five days later, his HIV RNA was reported as positive (559 copies/mL). He was notified of the result, linked to care and immediately started antiretroviral treatment (ART), at which point his RNA was 1544 copies/mL and his HIV Ab test was positive. The HIV genotype had M184V, L74V and K103N mutations and phenotypic susceptibility to TDF. TFV/FTC levels by LC-MS/MS measured in 1 cm segments of hair collected at ART initiation indicated consistently high PrEP adherence in each of the preceding 6 months. TFV-diphosphate and FTC-triphosphate levels in DBS collected 2 days after ART initiation were 1012 fmol/punch and 0.266 pmol/punch, confirming high adherence over the preceding 6 weeks. Between PrEP initiation and HIV acquisition, he had 1 episode of urethral chlamydia and three episodes of urethral gonorrhea. The likely transmission partner, named during PS, had no history of viral suppression in HIV surveillance and harbored the same resistance mutations, with a genetic distance between the two patients of 0.66%. The partner was re-linked to care and had a current HIV RNA of 15,130 copies/mL. Conclusion Acquisition of TDF-susceptible HIV infection can occur despite high PrEP adherence. Quarterly HIV and STD screening of patients on PrEP, combined with prompt linkage to care and PS for those diagnosed with HIV, facilitates early diagnosis and prevents further transmission of HIV. Disclosures S. E. Cohen, Gilead: Investigator in PrEP study for which Gilead donated drug, donated study drug and paid for drug testing during the PrEP demo project, of which I was a co-PI (the study has ended). S. Lee, Viiv Healthcare: Investigator, Research grant. Gilead Sciences: Investigator, Research grant. P. Anderson, Gilead: Consultant and Investigator, funds were paid to the institution for contract work and grant support and Research support. D. Havlir, Gilead: Investigator, Gilead Sciences provides antiretroviral therapy for a NIH funded study that she is conducting and Research support.

Background Sexually transmitted infections (STI) in people living with HIV (PLWH) and HIV-uninfected men who have sex with men (MSM) are increasing. Doxycycline post-exposure prophylaxis (doxy-PEP) showed partial efficacy against STI acquisition in a small population of HIV-uninfected MSM using pre-exposure prophylaxis (PrEP). Acceptability in a larger, diverse population of MSM is unknown. Methods We conducted a survey of doxycycline for STI PEP among users of a gay social networking app in 6 US cities: Atlanta, Birmingham, Chicago, New York City, San Francisco, and Seattle. In adjusted analyses using logistic regression, we examined factors associated with bacterial STI in the last year and willingness to use doxy-PEP. Predictors included: demographics, city, risk behaviors, and bacterial STI. Results Overall, 1301 individuals, 80% HIV-uninfected, 16% PLWH, and 4% status unknown responded to the survey. The median age was 33 and the sample was racially/ethnically diverse: 7% Asian, 21% Black, 24% Latinx, and 44% White. Most (80%), reported condomless sex in the last 6 months; 39% reported an STI in the last year. Of the HIV-uninfected, 44% were on PrEP. In adjusted analysis, age per ten years was inversely associated with an STI in the last year (AOR 0.8; 95% CI: 0.7–0.9 and AOR 0.2; 0.0–0.8 respectively), while number of partners in the last 6 months and condomless anal sex were associated with STI (AOR 1.1 per 5 partners; 1.0–1.1 and AOR 3.8; 2.5–5.8 respectively). There was no difference by race/ethnicity, or when comparing PrEP users to PLWH, however not using PrEP was inversely associated with STI (AOR 0.2; 0.2–0.3). Overall, 84% of respondents were interested in trying doxy-PEP. The factors associated with higher interest were: older age per ten years (1.2; 95% CI 1.0–1.4), Black race and Latinx ethnicity vs. White race (AOR 2.0; 1.2–3.5 and 1.9; 1.2–3.0 respectively), prior STI (AOR 1.7; 1.1–2.5), and having condomless sex (AOR 1.6; 1.1–2.4). Interest did not differ by city, number of partners, serostatus, or PrEP use. Conclusion Interest in doxy-PEP was high among a diverse population of MSM in the US Differences in reported STI prevalence may be related to increased detection through screening in PLWH and on PrEP. Additional research to evaluate efficacy/safety of doxy-PEP is needed to potentially reduce STIs among MSM. Disclosures All authors: No reported disclosures.

Author(s): Chen, Iris; Chau, Gordon; Wang, Jing; Clarke, William; Marzinke, Mark A; Cummings, Vanessa; Breaud, Autumn; Laeyendecker, Oliver; Fields, Sheldon D; Griffith, Sam; Scott, Hyman M; Shoptaw, Steven; Del Rio, Carlos; Magnus, Manya; Mannheimer, Sharon; Tieu, Hong-Van; Wheeler, Darrell P; Mayer, Kenneth H; Koblin, Beryl A; Eshleman, Susan H | Abstract: BackgroundHIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study.MethodsA high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study) visits.ResultsMen with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity) than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions) and HIV drug resistance (both gag regions) were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment.ConclusionsHIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load.

Pre-Exposure Prophylaxis (PrEP) has shown high efficacy in preventing human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) in several large clinical trials, and more recently in “real world” reports of clinical implementation and a PrEP demonstration project. Those studies also demonstrated high bacterial sexually transmitted infection (STI) incidence and raised the discussion of how PrEP may impact STI control efforts, especially in the setting of increasing Neisseria gonorrhoeae antimicrobial resistance and the increase in syphilis cases among MSM. Here, we discuss STIs as a driver of HIV transmission risk among MSM, and the potential opportunities and challenges for STI control afforded by expanded PrEP implementation among high-risk MSM.

HIV Prevention Trials Network (HPTN) 061 enrolled black men who have sex with men in the United States. Some men with low/undetectable HIV RNA had unusual patterns of antiretroviral (ARV) drug use or had drugs detected in the absence of viral suppression. This report includes a comprehensive analysis of ARV drug use and drug resistance among men in HPTN 061 who were not virally suppressed.The analysis included 169 men who had viral loads400 copies per milliliter at enrollment, including 3 with acute infection and 13 with recent infection. By self-report, 88 were previously diagnosed, including 31 in care; 137 men reported no ARV drug use. Samples from these 169 men and 23 seroconverters were analyzed with HIV genotyping and ARV drug assays.Forty-eight (28%) of the 169 men had ≥ 1 drug resistance mutation (DRM); 19 (11%) had multiclass resistance. Sixty men (36%) had ≥ 1 ARV drug detected, 42 (70%) of whom reported no ARV drug use. Nine (23%) of 39 newly infected men had ≥ 1 DRM; 10 had ≥ 1 ARV drug detected. Unusual patterns of ARV drugs were detected more frequently in newly diagnosed men than previously diagnosed men. The rate of transmitted drug resistance was 23% based on HIV genotyping and self-reported ARV drug use but was 12% after adjusting for ARV drug detection.Many men in HPTN 061 had drug-resistant HIV, and many were at risk of acquiring additional DRMs. ARV drug testing revealed unusual patterns of ARV drug use and provided a more accurate estimate of transmitted drug resistance.

African American men who have sex with men have been disproportionately affected by the HIV epidemic in the United States and remain to this day one of the groups with highest HIV prevalence and incidence. Our goal was to clarify the current state of HIV risk, sexual behaviors, and structural/network–network level factors that affect black MSM’s population risk of HIV, enabling the formulation of targeted and up-to-date public health messages/campaigns directed at this vulnerable population. Our approach maximized the use of local data through a process of synthesis and triangulation of multiple independent and overlapping sources of information that are sometimes separately published and often not examined side-by-side. Among African American MSM, we observed stable HIV incidence despite increases in reported individual risk behavior and STDs. An increasing proportion of African American MSM are reporting HIV testing in the past 6 months and seroadaptive behaviors, which may play a role in this observed decline in HIV among MSM in San Francisco, California. Our analysis suggests that currently the HIV epidemic is stable among African American MSM in San Francisco. However, we suggest that the observed stability is due to factors prohibiting expansion of new infections rather than decreasing risks for HIV infection among African American MSM.