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BACKGROUND: Interventions to reduce sexually transmitted infections (STIs) among men who have sex with men (MSM) are needed. METHODS: We conducted an open-label, randomized study involving MSM and transgender women who were taking preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) infection (PrEP cohort) or living with HIV infection (persons living with HIV infection [PLWH] cohort) and who had had Neisseria gonorrhoeae (gonorrhea), Chlamydia trachomatis (chlamydia), or syphilis in the past year. Participants were randomly assigned in a 2:1 ratio to take 200 mg of doxycycline within 72 hours after condomless sex (doxycycline postexposure prophylaxis) or receive standard care without doxycycline. STI testing was performed quarterly. The primary end point was the incidence of at least one STI per follow-up quarter. RESULTS: Of 501 participants (327 in the PrEP cohort and 174 in the PLWH cohort), 67% were White, 7% Black, 11% Asian or Pacific Islander, and 30% Hispanic or Latino. In the PrEP cohort, an STI was diagnosed in 61 of 570 quarterly visits (10.7%) in the doxycycline group and 82 of 257 quarterly visits (31.9%) in the standard-care group, for an absolute difference of -21.2 percentage points and a relative risk of 0.34 (95% confidence interval [CI], 0.24 to 0.46; P

BackgroundAfter coronavirus disease 2019 (COVID-19) shelter-in-place (SIP) orders, viral suppression (VS) rates initially decreased within a safety-net human immunodeficiency virus (HIV) clinic in San Francisco, particularly among people living with HIV (PLWH) who are experiencing homelessness. We sought to determine if proactive outreach to provide social services, scaling up of in-person visits, and expansion of housing programs could reverse this decline.MethodsWe assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression followed by interrupted time series (ITS) analysis to examine changes in the rate of VS per month. Loss to follow-up (LTFU) was assessed via active clinic tracing.ResultsData from 1816 patients were included; the median age was 51 years, 12% were female, and 14% were experiencing unstable housing/homelessness. The adjusted odds of VS increased 1.34 fold following institution of the multicomponent strategies (95% confidence interval [CI], 1.21-1.46). In the ITS analysis, the odds of VS continuously increased 1.05 fold per month over the post-intervention period (95% CI, 1.01-1.08). Among PLWH who previously experienced homelessness and successfully received housing support, the odds of VS were 1.94-fold higher (95% CI, 1.05-3.59). The 1-year LTFU rate was 2.8 per 100 person-years (95% CI, 2.2-3.5).ConclusionsThe VS rate increased following institution of the multicomponent strategies, with a lower LFTU rate compared with prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing programs, will be needed to support VS among underserved populations during the COVID-19 pandemic.

BackgroundIn 2010-2014, the San Francisco Department of Public Health (SFDPH) established programs to rapidly link people with human immunodeficiency virus (PWH) to care and offer antiretroviral therapy (ART) at human immunodeficiency virus (HIV) diagnosis. Such programs reduced the number of PWH out of care or with detectable HIV viral load (ie, uncontrolled HIV infection). We investigated the role of social determinants of health (SDH) on uncontrolled HIV.MethodsCross-sectional data from adult PWH diagnosed and reported to the SFDPH as of December 31, 2019, prescribed ART, and with confirmed San Francisco residency during 2017-2019 were analyzed in conjunction with SDH metrics derived from the American Community Survey 2015-2019. We focused on 5 census tract-level SDH metrics: percentage of residents below the federal poverty level, with less than a high school diploma, or uninsured; median household income; and Gini index. We compared uncontrolled HIV prevalence odds ratios (PORs) across quartiles of each metric independently using logistic regression models.ResultsThe analysis included 7486 PWH (6889 controlled HIV; 597 uncontrolled HIV). Unadjusted PORs of uncontrolled HIV rose with increasingly marginalized quartiles, compared to the least marginalized quartile for each metric. Adjusting for demographics and transmission category, the POR for uncontrolled HIV for PWH in the most marginalized quartile remained significant across metrics for poverty (POR = 2.0; confidence interval [CI] = 1.5-2.6), education (POR = 2.4; CI = 1.8-3.2), insurance (POR = 1.8; CI = 1.3-2.5), income (POR = 1.8; CI = 1.4-2.3), and income inequality (POR = 1.5; CI = 1.1-2.0).ConclusionsBeyond demographics, SDH differentially affected the ability of PWH to control HIV. Despite established care programs, PWH experiencing socioeconomic marginalization require additional support to achieve health outcome goals.

BackgroundThe safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.MethodsIn this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.ResultsA total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P

BackgroundKey components of Ending the HIV Epidemic (EHE) plan include increasing HIV antiretroviral therapy (ART) and HIV pre-exposure prophylaxis (PrEP) coverage. One complication to addressing this service delivery challenge is the wide heterogeneity of HIV burden and health care access across the United States. 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 2 counterfactual levels. We assessed the effectiveness of PrEP with the cumulative percentage of infections averted (PIA) over the next decade and efficiency with the number of additional person-years 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. Indeed, the PIA was 61% in the lowest baseline ART coverage population and 75% in the highest. 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 such as San Francisco. Efforts should focus on narrowing the implementation gaps to achieve higher levels of PrEP retention and ART sustained viral suppression.

To assess SARS-CoV-2 outcomes, we matched a municipal COVID-19 registry and clinic rosters from a municipal primary care network containing a large HIV clinic and assessed clinical outcomes by HIV status. The risk of severe COVID-19 was higher among people with HIV (PWH, adjusted relative risk = 1.84, 95% confidence interval = 1.05-3.25), while SARS-CoV-2 incidence was lower despite higher testing rates. SARS-CoV-2 vaccination campaigns should prioritize PWH to prevent severe COVID-19 disease given potentially higher risk.

ObjectivesInaccuracies in cause-of-death information in death certificates can reduce the validity of national death statistics and result in poor targeting of resources to reduce morbidity and mortality in people with HIV. Our objective was to measure the sensitivity, specificity, and agreement between multiple causes of deaths from death certificates obtained from the National Death Index (NDI) and causes determined by expert physician review.MethodsPhysician specialists determined the cause of death using information collected from the medical records of 50 randomly selected HIV-infected people who died in San Francisco from July 1, 2016, through May 31, 2017. Using expert review as the gold standard, we measured sensitivity, specificity, and agreement.ResultsThe NDI had a sensitivity of 53.9% and a specificity of 66.7% for HIV deaths. The NDI had a moderate sensitivity for non-AIDS-related infectious diseases and non-AIDS-related cancers (70.6% and 75.0%, respectively) and high specificity for these causes (100.0% and 94.7%, respectively). The NDI had low sensitivity and high specificity for substance abuse (27.3% and 100.0%, respectively), heart disease (58.3% and 86.8%, respectively), hepatitis B/C (33.3% and 97.7%, respectively), and mental illness (50.0% and 97.8%, respectively). The measure of agreement between expert review and the NDI was lowest for HIV (κ = 0.20); moderate for heart disease (κ = 0.45) and hepatitis B/C (κ = 0.40); high for non-AIDS-related infectious diseases (κ = 0.76) and non-AIDS-related cancers (κ = 0.72); and low for all other causes of death (κ < 0.35).ConclusionsOur findings support education and training of health care providers to improve the accuracy of cause-of-death information on death certificates.

BackgroundEarly virologic suppression (VS) after human immunodeficiency virus (HIV) infection improves individual health outcomes and decreases onward transmission. In San Francisco, immediate antiretroviral therapy (ART) at HIV diagnosis was piloted in 2013-2014 and expanded citywide in 2015 in a rapid start initiative to link all new diagnoses to care within 5 days and start ART at the first care visit.MethodsHIV providers and linkage navigators were trained on a rapid start protocol with sites caring for vulnerable populations prioritized. Dates of HIV diagnosis, first care visit, ART initiation, and VS were abstracted from the San Francisco Department of Public Health HIV surveillance registry.ResultsDuring 2013-2017, among 1354 new HIV diagnoses in San Francisco, median days from diagnosis to first VS decreased from 145 to 76 (48%; P

Young men who have sex with men (YMSM) are highly vulnerable to HIV. While pre-exposure prophylaxis (PrEP) has demonstrated effectiveness, adherence has been low among YMSM and difficult to measure accurately. In collaboration with a healthcare company, we configured an automated directly-observed therapy (aDOT) platform for monitoring and supporting PrEP use. Based on interest expressed in focus groups among 54 YMSM, we combined aDOT with an electronic sexual diary to provide feedback on level of protection during sex and to motivate app use. In an 8-week optimization pilot with 20 YMSM in San Francisco and Atlanta, the app was found to be highly acceptable, with median System Usability Scale scores in the "excellent" range (80/100). App use was high, with median PrEP adherence of 91% based on aDOT-confirmed dosing. Most (84%) participants reported the app helped with taking PrEP. These promising findings support further evaluation of DOT Diary in future effectiveness studies.

BackgroundYoung 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.MethodsData 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.ResultsParticipants 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.ConclusionsHIV 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.

ImportanceData on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices.ObjectiveTo evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV.Evidence reviewNew evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations.FindingsFrom 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic.Conclusion and relevanceAdvances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.

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 6 months 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 (

BackgroundBuilding on several decades of innovative HIV prevention and treatment programming in San Francisco, in 2014, a small group of academic, civic, and community leaders launched Getting to Zero San Francisco, a city-wide consortium focused on getting to zero HIV infections, zero HIV-related deaths, and zero HIV stigma and discrimination.SettingSan Francisco city and county.MethodsThe consortium operates under the principles of collective impact composed of 5 components: a common agenda, shared measurement, mutually reinforcing activities, continuous communication, and organization backbone. Two flagship initiatives are described: citywide scale-up of pre-exposure prophylaxis and rapid antiretroviral therapy upon diagnosis.ResultsThe number of new HIV diagnoses declined by over 50% from 399 to 197 from 2013 to 2018; the time from diagnosis to viral suppression decreased from 134 to 62 days during that period. However, continued racial/ethnic disparities in new HIV diagnoses and viral suppression rates point to the need for the Getting to Zero San Francisco committees to focus on racial/ethnic equity as a primary focus. Cisgender and transgender women, people who inject drugs, and people who are homeless also have lower viral suppression rates; ongoing initiatives are attempting to address these disparities.ConclusionA collective impact implementation strategy that operates by unifying municipal organizations toward a common goal was associated with citywide gains in reducing new HIV diagnosis and time to viral suppression in San Francisco. Formal evaluation of this strategy will help elucidate under which conditions this approach is most likely to succeed.

ObjectiveSan Francisco, California, has experienced a 44% reduction in new HIV diagnoses since 2013 supported by its 'Getting to Zero' initiative; however, the age-adjusted mortality rate in people with HIV (PWH) has not decreased. We sought to identify factors associated with death among PWH in San Francisco.DesignPopulation-based incidence-density case-control study.MethodsAmong PWH in the San Francisco HIV surveillance registry, a random sample of 48 decedents from 1 July 2016 to 31 May 2017 were each matched to two to three controls who were alive at the date of death (108 controls matched on age and time since diagnosis). Covariates included demographics, substance use, housing status, medical conditions, and care indicators from the study population. We used matched-pair conditional logistic regression to examine factors associated with mortality.ResultsOf the 156 PWH in the study, 14% were African-American, 14% Latino, and 8% female sex. In adjusted analysis, factors associated with higher odds of death included: homelessness at HIV diagnosis [adjusted odds ratio (AOR) = 27.4; 95% confidence interval (CI) = 3.0-552.1], prior-year IDU (AOR = 10.2; 95% CI = 1.7-128.5), prior-year tobacco use (AOR = 7.2; 95% CI = 1.7-46.9), being off antiretroviral therapy at any point in the prior year (AOR = 6.8; 95% CI = 1.1-71.4), and being unpartnered vs. married/partnered (AOR = 4.7; 95% CI = 1.3-22.0).ConclusionPeople homeless at HIV diagnosis had 27-fold higher odds of death compared with those with housing; substance use and retention on antiretroviral therapy in the prior year are other important intervenable factors. New strategies to address these barriers, and continued investment in supportive housing and substance use treatment, are needed.

Bone mineral density (BMD) declines due to tenofovir-containing pre-exposure prophylaxis (PrEP) have varied among PrEP demonstration projects, potentially related to variable adherence. Characterization of BMD changes in highly adherent individuals, estimated via tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS), can assist clinicians when counseling patients. Cisgender men who have sex with men and transwomen in the optional dual-energy X-ray absorptiometry (DXA) substudy of a large, international, open-label PrEP demonstration project, the iPrEx-open-label extension (OLE) study underwent DXA scans and DBS collection every 24 weeks, with average weekly dosing adherence patterns (2, 4, and 7 doses/week) estimated from validated TFV-DP cut-offs. The mean percent BMD change was estimated in strata of average weekly adherence by using a linear mixed-effects model to calculate the BMD decline in highly adherent individuals on PrEP for the first time. DXA/DBS data were available for 254 individuals over a median of 24 weeks in iPrEx-OLE from June 2011 to December 2013. The percent decline in spine BMD was monotonically associated with strata of increasing average weekly adherence (p

The HIV Research for Prevention (HIVR4P) conference is dedicated to advancing HIV prevention research, responding to a growing consensus that effective and durable prevention will require a combination of approaches as well as unprecedented collaboration among scientists, practitioners, and community workers from different fields and geographic areas. The conference theme in 2018, "From Research to Impact," acknowledged an increasing focus on translation of promising research findings into practical, accessible, and affordable HIV prevention options for those who need them worldwide. HIVR4P 2018 was held in Madrid, Spain, on 21-25 October, with >1,400 participants from 52 countries around the globe, representing all aspects of HIV prevention research and implementation. The program included 137 oral and 610 poster presentations. This article presents a brief summary of highlights from the conference. More detailed information, complete abstracts as well as webcasts and daily Rapporteur summaries may be found on the conference website.

BACKGROUND:Objective adherence metrics for tenofovir (TFV) disoproxil fumarate/emtricitabine(FTC)-based 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 (POC) 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 non-retention is unknown. SETTING:Secondary data analysis of a large, prospective multi-site U.S. PrEP demonstration project METHODS:: 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 non-retention. RESULTS:Overall, 294 individuals (median age 33 years) contributed drug levels within the U.S. PrEP demonstration project. By study end, 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 sub-optimal long-term adherence (TFV-DP

BackgroundPeople living with HIV (PLWH) who experience homelessness and unstable housing (HUH) often have fragmented health care. Research that incorporates granular assessments of housing status and primary care visit adherence to understand patterns of acute care utilization can help pinpoint areas for intervention.MethodsWe collected self-reported living situation, categorized as stable (rent/own, hotel/single room occupancy), unstable (treatment/transitional program, staying with friends), or homeless (homeless shelter, outdoors/in vehicle) at an urban safety-net HIV clinic between February and August 2017 and abstracted demographic and clinical information from the medical record. Regression models evaluated the association of housing status on the frequency of acute care visits-urgent care (UC) visits, emergency department (ED) visits, and hospitalizations-and whether suboptimal primary care visit adherence (

ObjectiveWe examined the relationship between urine tenofovir (TFV) levels measured with a novel immunoassay, which permits point-of-care testing, with HIV seroconversion and objective adherence metrics in a large preexposure prophylaxis (PrEP) demonstration project.DesignSecondary analysis of stored specimens from an open-label PrEP cohort study.MethodsWe examined the association between undetectable urine TFV levels and HIV seroconversion in iPrEx open-label extension using generalized estimating equations. We examined rank correlations between levels of TFV and emtricitabine in urine, dried blood spots (DBS), and hair and determined the sensitivity and specificity of undetectable urine TFV for predicting dosing cut-offs in DBS.ResultsThe median urinary TFV level was 15 000 ng/ml in those who remained HIV-negative (n = 105; interquartile range: 1000-45 000); 5500 in those who eventually seroconverted (n = 11; interquartile range: 1000-12 500); and all were undetectable at seroconversion (n = 9; P

IntroductionDeveloping guidelines to inform the use of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention in resource-limited settings must necessarily be informed by considering the resources and infrastructure needed for PrEP delivery. We describe an approach that identifies subpopulations of cisgender men who have sex with men (MSM) and transgender women (TGW) to prioritize for the rollout of PrEP in resource-limited settings.MethodsWe use data from the iPrEx study, a multi-national phase III study of PrEP for HIV prevention in MSM/TGW, to build statistical models that identify subpopulations at high risk of HIV acquisition without PrEP, and with high expected PrEP benefit. We then evaluate empirically the population impact of policies recommending PrEP to these subpopulations, and contrast these with existing policies.ResultsA policy recommending PrEP to a high risk subpopulation of MSM/TGW reporting condomless receptive anal intercourse over the last 3 months (estimated 3.3% 1-year HIV incidence) yields an estimated 1.95% absolute reduction in 1-year HIV incidence at the population level, and 3.83% reduction over 2 years. Importantly, such a policy requires rolling PrEP out to just 59.7% of MSM/TGW in the iPrEx population. We find that this policy is identical to that which prioritizes MSM/TGW with high expected PrEP benefit. It is estimated to achieve nearly the same reduction in HIV incidence as the PrEP guideline put forth by the US Centers for Disease Control, which relies on the measurement of more behavioral risk factors and which would recommend PrEP to a larger subset of the MSM/TGW population (86% vs. 60%).ConclusionsThese findings may be used to focus future mathematical modelling studies of PrEP in resource-limited settings on prioritizing PrEP for high-risk subpopulations of MSM/TGW. The statistical approach we took could be employed to develop PrEP policies for other at-risk populations and resource-limited settings.

ImportanceAntiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection.ObjectiveTo evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk.Evidence reviewNew evidence collected since the International Antiviral Society-USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations.FindingsART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV.Conclusions and relevanceAdvances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.

BackgroundAntiretroviral drugs have been associated with changes in lipids, fat mass and dat distribution. Tenofovir disoproxil fumarate (TDF) has been shown to have a more favorable metabolic profile than other drugs in its class. However, the metabolic effects of TDF in preexposure prophylaxis (PrEP) are unknown.MethodsWe evaluated the effects of TDF/emtricitabine (FTC) on lipids and body composition in a blinded, placebo-controlled PrEP trial. Participants enrolled in a metabolic subcohort (N = 251, TDF/FTC; N = 247, placebo) consented to fasting lipid panels, dual-energy X-ray absorptiometry scans for body composition, and pharmacologic testing of drug metabolites at baseline and every 24 weeks thereafter.ResultsLean body mass was stable and unaffected by TDF/FTC. Body weight increased in both groups but was lower on TDF/FTC through week 72. This difference was explained by lower fat accumulation on TDF/FTC. The net median percent difference (standard error, P value) for TDF/FTC vs placebo at week 24 was -0.8% (0.4%, P = .02), +0.3% (0.4%, P = .46), and -3.8% (1.4%, P = .009) for total, lean, and fat mass, respectively. There was no apparent differential regional fat accumulation on TDF/FTC. Decreases in cholesterol, but not triglycerides, were seen in TDF/FTC participants, with detectable drug levels compared to placebo.ConclusionsTDF/FTC for PrEP showed cholesterol reductions and appeared to transiently suppress the accumulation of weight and body fat compared to placebo. There was no evidence of altered fat distribution or lipodystrophy during daily oral TDF/FTC PrEP.Clinical trials registrationNCT00458393.

BackgroundSan Francisco has launched interventions to reduce new human immunodeficiency virus (HIV) infections and HIV-associated morbidity and mortality during the San Francisco "Getting to Zero" era. We measured recent changes in HIV care indicators to assess the success of these interventions.MethodsSan Francisco residents with newly diagnosed HIV infection, diagnosed from 2009 to 2014, were included. We measured temporal changes from HIV diagnosis to (1) linkage to care in within ≤3 months, (2) initiation of antiretroviral therapy (ART) within ≤12 months, (3) viral suppression within ≤12 months, (4) development of AIDS within ≤3 months, (5) death within ≤12 months, and (6) retention in care 6-12 months after linkage. Kaplan-Meier analyses stratified by year of HIV diagnosis measured time from diagnosis to linkage, ART initiation, viral suppression, AIDS, and death.ResultsOverall, the number of new diagnoses declined from 473 in 2009 to 329 in 2014. The proportion of new diagnoses among men (P = .005), Latinos and Asian/Pacific Islanders (P = .02), and men who have sex with men (P = .003) increased. ART initiation and viral suppression ≤12 months after diagnosis increased (P < .001), while the proportion with AIDS diagnosed ≤3 months after HIV diagnosis declined (P < .001). Time to ART initiation and time to viral suppression were significantly shorter in more recent years of diagnosis (P < .001). Time from HIV to AIDS diagnosis was significantly longer in more recent years (P < .001). Retention in care did not significantly change.ConclusionsIn San Francisco new HIV diagnoses have declined and HIV care indicators have improved during the Getting to Zero era. Continued success requires attention to vulnerable populations and monitoring to adjust programmatic priorities.

Housing instability negatively impacts outcomes in people [living] with human immunodeficiency virus (PLHIV), yet the effect of diverse living arrangements has not previously been evaluated. Using 6 dwelling types to measure housing status, we found a strong inverse association between housing instability and viral suppression across a spectrum of unstable housing arrangements.

The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.IMPORTANCE CD8+ T cells play a central role in successful control of HIV infection and have the potential also to mediate the eradication of viral reservoirs of infection. The principal means by which protective HLA class I molecules, such as HLA-B*27:05 and HLA-B*57:01, slow HIV disease progression is believed to be via the particular HIV-specific CD8+ T cell responses restricted by those alleles. We focus here on HLA-B*27:05, one of the best-characterized protective HLA molecules, and the closely related HLA-B*27:02, which differs by only 3 amino acids and which has not been well studied in relation to control of HIV infection. We show that HLA-B*27:02 is also protective against HIV disease progression, but the CD8+ T-cell immunodominance hierarchy of HLA-B*27:02 differs strikingly from that of HLA-B*27:05. These findings indicate that the immunodominant HLA-B*27:02-restricted Nef response adds to protection mediated by the Gag and Pol specificities that dominate anti-HIV CD8+ T-cell activity in HLA-B*27:05-positive subjects.

BackgroundHIV preexposure prophylaxis (PrEP) using daily oral tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) is effective for preventing HIV acquisition, but concerns remain about its potential kidney toxicity. This study examined kidney function in individuals using PrEP in real-world clinical settings.SettingDemonstration project in 2 sexually transmitted infection clinics and a community health center.MethodsWe evaluated kidney function among men who have sex with men and transgender women taking tenofovir-disoproxil-fumarate/emtricitabine PrEP for up to 48 weeks. Serum creatinine and urine dipstick for protein were obtained at 12-week intervals. Kidney function was estimated using creatinine clearance (CrCl) (Cockcroft-Gault) and estimated glomerular filtration rate (eGFR) (CKD-EPI).ResultsFrom October 2012 to January 2014, we enrolled 557 participants (median age 33). Mean creatinine increased from baseline to week 12 by 0.03 mg/dL (4.6%) (P < 0.0001); mean CrCl decreased by 4.8 mL/min (3.0%) (P < 0.0001). These changes remained stable through week 48 (P = 0.81, P = 0.71 respectively). There were 75/478 (15.7%) participants who developed worsening proteinuria at week 12 compared with baseline (P < 0.0001), and this percent remained stable through week 48 (P = 0.73). Twenty-five participants (5.1%) developed new-onset eGFR

Clinical trial registrationClinical Trials.gov NCT00131677.

The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A-derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor. HLA-B haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease.

BackgroundIt is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART.Methods and findingsColorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs) were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA). Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative) followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse), but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input cells/mouse) experienced very low level viremia (201 copies/mL); sequence confirmation was unsuccessful. PrEP Participant A stopped ART and remained aviremic for 7.4 months, rebounding with HIV RNA of 36 copies/mL that rose to 59,805 copies/mL 6 days later. ART was restarted promptly. Rebound plasma HIV sequences were identical to those obtained during acute infection by single-genome sequencing. Mathematical modeling predicted that the latent reservoir size was approximately 200 cells prior to ATI and that only around 1% of individuals with a similar HIV burden may achieve lifelong ART-free remission. Furthermore, we observed that lymphocytes expressing the tumor marker CD30 increased in frequency weeks to months prior to detectable HIV-1 RNA in plasma. This study was limited by the small sample size, which was a result of the rarity of individuals presenting during hyperacute infection.ConclusionsWe report HIV relapse despite initiation of ART at one of the earliest stages of acute HIV infection possible. Near complete or complete loss of detectable HIV in blood and tissues did not lead to indefinite ART-free HIV remission. However, the small numbers of latently infected cells in individuals treated during hyperacute infection may be associated with prolonged ART-free remission.

ObjectiveThe US preexposure prophylaxis (PrEP) Demonstration Project (U.S. Demo) evaluated MSM on PrEP postmarketing and found low seroconversion rates. The objective of this study is to examine hair levels as an adherence measure to PrEP.DesignUsing an 'opt-in' design, participants of PrEP Demo were invited to enroll into a substudy where hair was collected quarterly.MethodsTenofovir concentrations were measured in hair by liquid chromatography/tandem mass spectrometry. Hair levels consistent with ≥4 doses/week (protective in other studies) defined adequate adherence. Mixed effects multivariate logistic regression models examined factors associated with ≥4 doses/week. Separate mixed effects models evaluated the relationship between hair PrEP levels and changes in creatinine clearance (CrCl) over time.ResultsOverall, 58% of U.S. Demo participants enrolled into this opt-in study; reasons for nonparticipation included insufficient hair (61%) and concerns about hairstyle (27%). Hair and dried blood spots levels consistent with ≥4 doses/week were highly concordant (84%). Hair levels showed adequate adherence in 87% of 875 person-visits (among 280 participants). Factors associated with adequate adherence in multivariate models were amphetamine use [adjusted odds ratio (aOR) 2.59 (0.97-6.9, P 0.06)], condomless receptive anal sex [aOR 2.28 (1.19-4.40, P 0.01)], and stable housing [aOR 2.63 (1.03-6.67), P 0.04]. Hair levels of tenofovir showed a monotonic relationship with decline in CrCl (P 0.01 for trend).ConclusionIn this substudy of the U.S. PrEP demonstration project, hair and dried blood spots levels were highly concordant and hair concentrations demonstrated adequate adherence 87% of the time, with stable housing and high-risk behavior associated with higher adherence. Daily PrEP drug taking is associated with modest declines in CrCl.

BackgroundOral tenofovir disoproxil fumarate (TDF) for HIV prevention and treatment is associated with decreases in bone mineral density (BMD). Previous reports suggest that these changes may be reversible after discontinuation of TDF.SettingA metabolic substudy of 498 participants in a randomized, placebo-controlled HIV prevention trial of oral coformulated TDF with emtricitabine (TDF/FTC, Truvada) for HIV pre-exposure prophylaxis (PrEP) enrolling a global sample of men who have sex with men and trans women.MethodsParticipants underwent dual X-ray absorptiometry to quantify bone mineral density (BMD) in the hip and spine during PrEP and at 2 visits after stopping (median of 23 and 79 weeks post-PrEP, respectively). Results are stratified by pharmacologic measure of TDF/FTC adherence.ResultsThere was no significant difference in change in hip/spine BMD at any time point between placebo and those with low adherence. Adherent participants had a mean (standard error) BMD change at TDF/FTC discontinuation of -1.02% (0.24) in the hip and -1.84% (0.36) in the spine. After stop, annualized BMD increases of 1.13% per year (0.27) in hip and 1.81% per year (0.36) in spine BMD were observed in adherent participants compared with 0.19% (0.16) and 0.74% (0.21) in the placebo group, respectively (P = 0.003, both comparisons). On average, BMD returned to baseline levels by 1 year after PrEP stop. Recovery was consistent across age, baseline BMD z-score, and treatment duration.ConclusionsMean BMD returns to baseline levels within 12-18 months after TDF-based PrEP discontinuation in both hip and spine with consistency across participant subgroups.Clinical trials registrationclinicaltrials.gov NCT00458393.

Exchange sex and higher education were associated with an increased likelihood of international sexual partnerships (ISPs). Exchange sex and older age were associated with an increased likelihood of condomless sex in ISPs. Educational and socioeconomic factors may create unbalanced power dynamics that influence exchange sex and condomless sex in ISPs.

BackgroundAs pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine for the prevention of HIV infection is rolled out internationally, strategies to maintain effectiveness and to minimise adverse effects merit consideration. In this study, we aimed to assess reductions in renal function and predictors of renal toxicity in a large open-label study of PrEP.MethodsAs part of the iPrEx open-label extension (OLE) study, men who have sex with men or transgender women aged 18-70 years who were HIV negative and had participated in three previous PrEP trials from Brazil, Ecuador, Peru, South Africa, Thailand, and the USA were enrolled into an open-label PrEP study. There were no restrictions on current renal function for enrolment into iPrEx OLE, in which participants were given combination tablets of tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) and advised to take one tablet per day. At follow-up sessions every 12 weeks, participants' creatinine clearance on PrEP was estimated and in a subset of participants, hair samples were collected to measure tenofovir and emtricitabine concentrations (a measure of adherence and exposure) via liquid-chromatography-tandem-mass-spectrometry. Reductions in creatinine clearance from baseline were calculated and predictors of decline were identified by use of multivariate models. iPrEx is registered with ClinicalTrials.com, number NCT00458393.FindingsBaseline characteristics were similar between all participants in iPrEx-OLE (1224 participants with 7475 person-visits) and those participating in the hair substudy (220 participants with 1114 person-visits). During a median of 72 weeks, the mean decline in creatinine clearance was -2·9% (95% CI -2·4 to -3·4; ptrend

HIV self-testing has the potential to increase testing frequency and uptake. This pilot study assessed the feasibility and acceptability of HIV self-testing in a sample of sexually active men who have sex with men (MSM) in Peru and Brazil. Participants were trained to use a whole blood rapid HIV self-test and instructed to use the self-test monthly during this three-month study. Test acceptability was measured with self-reported use of the test at the one-month and three-month study visits, and test feasibility was assessed by direct observation of self-test administration at the final three-month visit. A total of 103 participants (52 in Peru and 51 in Brazil) were enrolled, and 86% completed the three-month study. Nearly all participants reported use of the self-test (97% at one-month and 98% at three-month visit), and all participants correctly interpreted the self-administered test results when observed using the test at the final study visit. HIV self-testing with a blood-based assay was highly acceptable and feasible. HIV self-testing may have the potential to increase testing frequency and to reach high-risk MSM not currently accessing HIV-testing services.

BackgroundBlinded clinical trials have reported a modest and transient "start-up syndrome" with initiation of tenofovir-based pre-exposure prophylaxis (PrEP). We evaluate this phenomenon and its effect on adherence in an open-label PrEP study.MethodsIn the iPrEx open-label extension (OLE) study, an 18-month open-label, multi-site PrEP cohort taking daily oral co-formulated tenofovir/emtricitabine, we examined the prevalence and duration of PrEP-associated symptoms and their effect on adherence, assessed by drug levels in dried blood spots tested monthly for the first 3 months.ResultsSymptom reports peaked within the first month, with 39% reporting potentially PrEP-related symptoms compared to 22% at baseline. Symptoms largely resolved to pre-PrEP levels by 3 months.Symptoms varied substantially in frequency by study site (range in 1-month symptoms: 11% to 70%). Nongastrointestinal (GI) symptoms were not associated with adherence (odds ratio [OR] = 1.2, 95% confidence interval [CI], .4-3.7); however, GI-associated symptoms in the first 4 weeks were inversely associated with adherence at 4 weeks (OR = 0.47, 95% CI, .23-.96). Reports of GI symptoms were associated with 7% (95% CI, 4%-11%) of suboptimal adherence in this cohort.ConclusionsPrEP-associated symptoms in the open-label setting occur in a minority of users and largely resolve within 3 months. GI symptoms are associated with a modest reduction in PrEP adherence, but good adherence is possible even in the presence of frequent symptom reports.Clinical trials registrationClinicaltrials.govNCT00458393.

An estimated one in four transgender women (trans women) in the U.S. are infected with HIV. Rates of HIV testing are not commensurate with their risk, necessitating alternative strategies for early detection and care. We explored the feasibility and acceptability of HIV self-testing (HIVST) with 50 HIV-negative adult trans women in San Francisco. Participants received three self-test kits to perform once a month. Acceptability and behavioral surveys were collected as were 11 in-depth interviews (IDIs). Among 50 participants, 44 reported utilizing HIVST at least once; 94 % reported the test easy to use; 93 % said results were easy to read; and 91 % would recommend it to others. Most participants (68 %) preferred HIVST to clinic-based testing, although price was a key barrier to uptake. IDIs revealed a tension between desires for privacy versus support found at testing sites. HIVST for trans women was acceptable and feasible and requires careful consideration of linkage to support services.

We assessed whether economic, legal, and social hardships were associated with human immunodeficiency virus (HIV) risk among a sample of Black men who have sex with men (MSM) and whether associations were moderated by city of residence. The study analyzed baseline and follow-up data from HIV Prevention Trials Network 061 (N = 1553). Binary logistic regression assessed associations between hardships and HIV risk indicators. Multivariate regressions were used to test if city of residence had a moderating effect for hardships and HIV risks. Adjusted analyses showed that Black MSM with recent job loss were more likely to engage in condomless insertive anal intercourse (adjusted odds ratios (AOR) = 1.37, 95% CI 1.01-1.87) and that those with recent financial crisis were more likely to have had two or more male sexual partners in the past 6 months (AOR = 1.65; 95% CI 1.18-2.29). Black MSM with recent convictions were more likely to have a sexually transmitted infection at 6 months (AOR = 3.97; 95% CI 1.58-9.94), while those who were unstably housed were more likely to have a sexually transmitted infection at 12 months (AOR = 1.71; 95%CI 1.02 = 2.86). There were no city of residence and hardship interaction effects on HIV risks. Hardships are important factors that influence HIV risk for Black MSM. Integrating strategies that address structural factors that influence HIV risk may enhance HIV prevention interventions implementation efforts.

UnlabelledHuman leukocyte antigen (HLA) class I-associated polymorphisms in HIV-1 that persist upon transmission to HLA-mismatched hosts may spread in the population as the epidemic progresses. Transmission of HIV-1 sequences containing such adaptations may undermine cellular immune responses to the incoming virus in future hosts. Building upon previous work, we investigated the extent of HLA-associated polymorphism accumulation in HIV-1 polymerase (Pol) through comparative analysis of linked HIV-1/HLA class I genotypes sampled during historic (1979 to 1989; n = 338) and modern (2001 to 2011; n = 278) eras from across North America (Vancouver, BC, Canada; Boston, MA; New York, NY; and San Francisco, CA). Phylogenies inferred from historic and modern HIV-1 Pol sequences were star-like in shape, with an inferred most recent common ancestor (epidemic founder virus) sequence nearly identical to the modern North American subtype B consensus sequence. Nevertheless, modern HIV-1 Pol sequences exhibited roughly 2-fold-higher patristic (tip-to-tip) genetic distances than historic sequences, with HLA pressures likely driving ongoing diversification. Moreover, the frequencies of published HLA-associated polymorphisms in individuals lacking the selecting HLA class I allele was on average ∼2.5-fold higher in the modern than in the historic era, supporting their spread in circulation, though some remained stable in frequency during this time. Notably, polymorphisms restricted by protective HLA alleles appear to be spreading to a greater relative extent than others, though these increases are generally of modest absolute magnitude. However, despite evidence of polymorphism spread, North American hosts generally remain at relatively low risk of acquiring an HIV-1 polymerase sequence substantially preadapted to their HLA profiles, even in the present era.ImportanceHLA class I-restricted cytotoxic T-lymphocyte (CTL) escape mutations in HIV-1 that persist upon transmission may accumulate in circulation over time, potentially undermining host antiviral immunity to the transmitted viral strain. We studied >600 experimentally collected HIV-1 polymerase sequences linked to host HLA information dating back to 1979, along with phylogenetically reconstructed HIV-1 sequences dating back to the virus' introduction into North America. Overall, our results support the gradual spread of many-though not all-HIV-1 polymerase immune escape mutations in circulation over time. This is consistent with recent observations from other global regions, though the extent of polymorphism accumulation in North America appears to be lower than in populations with high seroprevalence, older epidemics, and/or limited HLA diversity. Importantly, the risk of acquiring an HIV-1 polymerase sequence at transmission that is substantially preadapted to one's HLA profile remains relatively low in North America, even in the present era.

ImportanceSeveral randomized clinical trials have demonstrated the efficacy of preexposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) acquisition. Little is known about adherence to the regimen, sexual practices, and overall effectiveness when PrEP is implemented in clinics that treat sexually transmitted infections (STIs) and community-based clinics serving men who have sex with men (MSM).ObjectiveTo assess PrEP adherence, sexual behaviors, and the incidence of STIs and HIV infection in a cohort of MSM and transgender women initiating PrEP in the United States.Design, setting, and participantsDemonstration project conducted from October 1, 2012, through February 10, 2015 (last date of follow-up), among 557 MSM and transgender women in 2 STI clinics in San Francisco, California, and Miami, Florida, and a community health center in Washington, DC. Data were analyzed from December 18, 2014, through August 8, 2015.InterventionsA combination of daily, oral tenofovir disoproxil fumarate and emtricitabine was provided free of charge for 48 weeks. All participants received HIV testing, brief client-centered counseling, and clinical monitoring.Main outcomes and measuresConcentrations of tenofovir diphosphate in dried blood spot samples, self-reported numbers of anal sex partners and episodes of condomless receptive anal sex, and incidence of STI and HIV acquisition.ResultsOverall, 557 participants initiated PrEP, and 437 of these (78.5%) were retained through 48 weeks. Based on the findings from the 294 participants who underwent measurement of tenofovir diphosphate levels, 80.0% to 85.6% had protective levels (consistent with ≥4 doses/wk) at follow-up visits. African American participants (56.8% of visits; P = .003) and those from the Miami site (65.1% of visits; P

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. Keywords: PrEP; HIV seroconversion; Adherence; PrEP persistence; mixed methods; PrEP discontinuation, 1 | INTRODUCTION Pre-exposure prophylaxis (PrEP) is a highly effective biomedical prevention strategy when taken during periods of HIV risk [1,2]. Although PrEP persistence (sustained PrEP use over time) was [...]

BackgroundDaily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women.MethodsDual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF.ResultsIn 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, -0.91% [95% confidence interval {CI}, -1.44% to -.38%]; P = .001) and hip (-0.61% [95% CI, -.96% to -.27%], P = .001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged -1.42% ± 29% and -0.85% ± 19% in the spine and hip, respectively (P < .001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P = .62) or incidence of low BMD.ConclusionsIn HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter.Clinical trials registrationNCT00458393.