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Background: Data characterising the long-term use and safety of emtricitabine plus tenofovir disoproxil fumarate as daily oral pre-exposure prophylaxis (PrEP) are scarce and there are uncertainties regarding the value of routine HIV-1 RNA testing during oral PrEP follow-up., Methods: The DISCOVER trial was a randomised, controlled, phase 3 trial in which cisgender men and transgender women aged 18 years and older with a high likelihood of acquiring HIV were recruited from 94 clinics in Europe and North America and randomly assigned to receive either emtricitabine plus tenofovir disoproxil fumarate (200/25 mg) tablets daily, with matched placebo tablets, or emtricitabine plus tenofovir alafenamide (200/300 mg) tablets daily, with matched placebo tablets, for at least 96 weeks. After completion of the trial, participants were offered enrolment in this 48-week open-label extension study of emtricitabine plus tenofovir alafenamide. In participants diagnosed with HIV during the randomised and open-label phases of the study, we characterised HIV-1 test results and measured HIV-1 RNA viral load retrospectively when available. Adherence based on tenofovir diphosphate concentrations in dried blood spots and genotypic resistance were assessed in participants diagnosed with HIV. Safety assessments included adverse events, laboratory parameters, and, in a subset of participants, bone mineral density. HIV-1 incidence in participants initially randomly assigned to receive emtricitabine plus tenofovir alafenamide was estimated using a Poisson distribution. Changes from baseline in safety endpoints were described in participants assigned to received emtricitabine plus tenofovir alafenamide and in those who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase. This trial is registered with ClinicalTrials.gov, NCT02842086, and is ongoing., Findings: Between Sept 13, 2016, and June 30, 2017, 5399 participants were enrolled and randomly assigned in DISCOVER. 2699 were assigned to receive emtricitabine plus tenofovir disoproxil fumarate and 2700 were assigned to receive emtricitabine plus tenofovir alafenamide, of whom 2693 and 2694, respectively, received at least one dose of study drug. 2115 (79%) assigned to emtricitabine plus tenofovir disoproxil fumarate switched to emtricitabine plus tenofovir alafenamide in the open-label phase, and 2070 (77%) continued with emtricitabine plus tenofovir alafenamide in the open-label phase. As of data cutoff (Dec 10, 2020), after 15 817 person-years of follow-up, 27 new HIV-1 diagnoses were observed across the total study period, with three occurring during the open-label phase. In participants who were initially assigned to emtricitabine plus tenofovir alafenamide, the incidence was 0·13 per 100 person-years (95% CI 0·061-0·23; ten of 2670). Stored plasma samples were available for 23 of 27 participants, including 22 with incident infection. In four (17%) of 23 participants, retrospective testing detected HIV-1 RNA before serological HIV-1 test positivity; one was a suspected baseline infection. Of the three incident cases, all three were non-adherent to PrEP and none developed drug resistance. Among participants taking emtricitabine plus tenofovir alafenamide for up to 144 weeks, markers of glomerular filtration and proximal renal tubule dysfunction (β2-microglobulin to creatinine ratio and retinol-binding protein to creatinine ratio) improved or remained stable at 144 weeks compared with baseline, bone mineral density in hip and lumbar spine increased or remained stable from baseline to week 144 (n=191), cholesterol and glucose concentrations remained stable, and median bodyweight increased by less than 1 kg per year. In participants who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase (2115 [79%] of 2693), markers of glomerular filtration and proximal renal tubule dysfunction improved or remained stable, bone mineral density increased, cholesterol concentrations increased, glucose concentrations were similar, and median bodyweight increased more compared with those who remained on emtricitabine and tenofovir alafenamide., Interpretation: Routine HIV-1 RNA testing for follow-up of individuals on daily oral PrEP provides modest additional clinical benefit. Long-term use of emtricitabine and tenofovir alafenamide as daily oral PrEP is safe and well tolerated and can be an especially appropriate choice for people with bone or renal morbidities., Funding: Gilead Sciences., Competing Interests: Declaration of interests DAW has received grants, consulting fees, and speaker honoraria from Gilead Sciences; grants from Merck; consulting fees and speaker honoraria from ViiV Healthcare; and consulting fees and speaker honoraria from Janssen Pharmaceuticals. CDS has received funding, grants, consulting fees, and non-financial support from Gilead Sciences; grants and speaker honoraria from AbbVie; grants and personal fees from Janssen-Cilag; grants and personal fees from MSD, ViiV Healthcare, BioNtech, and Eli Lilly; grants from Cepheid; grants, personal fees, and non-financial support from B Braun Melsungen; consulting fees from AstraZeneca; personal fees, non-financial support, and other support outside the submitted work from Apeiron Biologics; and personal fees from GSK, Formycon, Moderna, Molecular Partners, Novartis, Roche, Sobi, and Pfizer. JF, PJR, and RMG have received research funding from Gilead Sciences. CBH has received research grant support from Gilead Sciences. SD-L has received research grant support (paid to their institution) from Gilead Sciences and Merck. J-MM has received grants (paid to their institution) from Gilead Sciences and Merck; consulting fees from Gilead Sciences, Merck, and ViiV Healthcare; and payments for participation on an advisory board from AELIX Therapeutics. AM has received research funding (paid to their institution) from Gilead Sciences, ViiV Healthcare, Merck, GSK, AbbVie, and TaiMed Biologics; speaker honoraria from Gilead Sciences, ViiV Healthcare, and EMD Serono; and payments for participation on an advisory board from Gilead Sciences and ViiV Healthcare. CB has received funding and speaker honoraria from Gilead Sciences; speaker honoraria from ViiV Healthcare; and support for attending principal investigator meetings from Gilead Sciences, ViiV Healthcare, GSK, PPD (Thermo Fisher Scientific), Merck, Viking Therapeutics, Syneos Health, Novo Nordisk, AbbVie, Regeneron Pharmaceuticals, Janssen, and Shionogi. MR has received funding and speaker and consulting fees from Gilead Sciences, speaker and consulting fees from ViiV Healthcare, consulting fees from MSD and Abbott, and speaker honoraria from AbbVie and Janssen. AC has received advisory boards fees from Gilead Sciences, ViiV Healthcare, MSD, and Theratechnologies; funding for clinical trials (paid to their institution) from Gilead Sciences, MSD, GSK, ViiV Healthcare, and Pfizer; speaker fees from MSD; and support for congress attendance from Gilead Sciences and ViiV Healthcare. GC has received research funding (paid to their institution) from Gilead Sciences for conducting research discussed in this manuscript. CM has received funding and speaker fees from Gilead Sciences and grants and speaker fees from ViiV Healthcare and Theratechnologies. CC, SC, JCH, YS, MD, AK, and JMB are shareholders and employees of Gilead Sciences. KMo has received funding from Gilead Sciences; speaker fees and advisory board fees from Gilead Sciences, ViiV Healthcare, Janssen Therapeutics, Theratechnologies, and Epividian; and funding for clinical trials (paid to their institution) from Gilead Sciences, ViiV Healthcare, and Janssen Therapeutics. KMa has received research funding from Gilead Sciences, and unrestricted grants and advisory board fees from Gilead Sciences and Merck., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

There are approximately 90 000 lesbian, gay, bisexual, and transgender (LGBT) individuals in Orange County, California. LGBT individuals have significant health disparities, particularly if they are from racial or ethnic minority groups and/or have a disability. There are structural and access barriers in the health care system that increase these health disparities. These individuals experience discriminatory situations when accessing health care and mental health services, which may affect their health-seeking behaviors. The purpose of this pilot quantitative cross-sectional study was to gather information about the current health care experiences and needs of this LGBT population including priority health issues, physical and mental health care utilization, and perceived adequacy of LGBT-friendly physical and mental health care providers. These findings will inform organizational strategies for nursing administrators and other health care leaders when tailoring, planning, and redesigning structures that meaningfully address the service needs of this at-risk group. Seventy-five participants were recruited from 2 organizations serving the LGBT community to complete an online survey. Findings include trouble finding an LGBT competent provider, delays or being unable to access care, and worried about losing insurance. Most participants needed to visit multiple different locations to receive care and preferred a 1-stop shop., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: People living with HIV (PWH) have seen reduction in HIV-associated morbidity and increase in near-normal life expectancy, yet unhealthy alcohol use poses substantial risks to older as well as younger adults. Further research regarding age-associated physical and mental health concerns among PWH who drink alcohol is needed to inform services, given the expanding age range of patients in care. Methods: We compared age group differences (18-34, 35-44, 45-54, ≥55 years old) in two-year patient-reported outcomes and HIV viral control among PWH enrolled in a primary care-based behavioral alcohol intervention trial; with 90% follow up from baseline. Results: Of 553 PWH, 50 (9%) were 18-34, 85 (15%) were 35-44, 197 (36%) were 45-54, and 221 (40%) were ≥55 years old. Most were men (97%) and White (64%). At two years, PWH ≥55 reported less substance use in the prior 30 days, fewer social contacts, and more pain; younger PWH had lower antiretroviral therapy (ART) adherence. In adjusted analyses, PWH ages 18-34 had higher odds of unhealthy alcohol use, tobacco, cannabis, or other substances compared to those ≥55; with higher odds of anxiety among PWH 35-44 compared with those ≥55; and physical quality of life was worse among those ≥55 compared with younger groups. Conclusions: While older PWH report less substance use than younger PWH and have better ART adherence post-treatment, they are more likely to experience limited social support and worse physical quality of life. Findings can inform interventions to address varying needs of PWH across the lifespan.

Annual screening for bacterial sexually transmitted infections (STI), including gonorrhea/chlamydia (GC/CT) and syphilis, is recommended for persons with HIV (PWH). We used the prevention index to quantify the extent to which STI screening was completed at guideline-recommended frequency in African American and Latinx persons, women, persons with alcohol (AUD) and substance (SUD) use disorders. Data from PWH at Kaiser Permanente Northern California were collected from electronic health records. We defined receipt of GC/CT and syphilis screening consistent with recommendations as a prevention index score ≥ 75%. Among 9655 PWH (17.7% Latinx; 16.2% African American; 9.6% female; 12.4% AUD; 22.1% SUD), prevention index scores for GC/CT and syphilis increased from 2015 to 2019. African American PWH had lower odds of receiving an annual syphilis screen (aOR 0.87 [95% CI 0.79-0.97]). Female sex was associated with lower odds of GC/CT (aOR 0.30 [95% CI 0.27-0.34]) and syphilis (aOR 0.27 [95% CI 0.24-0.310) screening. AUD and SUD were not associated with differences in annual GC/CT or syphilis screening. Key PWH subgroups experience ongoing challenges to annual STI screening despite comparable healthcare access., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: 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., Design: 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., Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Black and Hispanic/Latinx cisgender men who have sex with men (MSM), transgender women, transgender men, and gender nonbinary (TGNB) individuals have been historically underrepresented in HIV pre-exposure prophylaxis (PrEP) clinical trials. There is an urgent need for ongoing engagement with communities that have been the most impacted by HIV and diverse representation in clinical trials. Here we describe strategic approaches undertaken in the PURPOSE 2 trial to optimize engagement of underrepresented individuals., Methods and Results: PURPOSE 2 is an ongoing Phase 3 trial evaluating the safety and efficacy of lenacapavir as PrEP in cisgender MSM and TGNB individuals. In PURPOSE 2, we used a multipronged approach aimed at enriching participation of underrepresented individuals. We conducted a review to identify evidence-informed recommendations from literature, engaged with stakeholders, and established the Global Community Advisory and Accountability Group (GCAG) to represent the needs of the community. Insights from stakeholders and GCAG members resulted in an expansion of the study population to include transgender men, gender nonbinary persons, and adolescents, and evaluation of population-specific outcomes. Feedback from stakeholders and GCAG members also informed investigator and site selection; these were selected based on prior experience working with persons from diverse racial, ethnic and gender identities, and estimates of local HIV incidence. Site selection was also expanded to include community-based clinics with services tailored towards Black, Hispanic/Latinx, and TGNB populations. We established a study-wide recruitment goal of 50% Black MSM and 20% Hispanic/Latinx MSM in US sites and 20% transgender women globally. Site-specific recruitment goals were also developed based on local demographics and HIV incidence. Mandatory trainings included Good Participatory Practice guidelines, gender inclusivity, and antiracism., Conclusion: While further work is needed to achieve equitable representation, the strategies we describe may serve as a framework for future clinical trials., Trial Registration: Clinical Trial Number: NCT04925752., Competing Interests: MC, JB, KM, MR, TH, and OO are investigators on this study and have received funding from Gilead Sciences. MD, JCH, AE, ACD, LC, CCW, CC, AK, and JMB are employees and shareholders of Gilead Sciences. JB reports grants paid to the University of California San Diego from Gilead Sciences and served on an advisory board for ViiV Healthcare. TH has served on speakers’ bureaus for Janssen, ViiV Healthcare, and Gilead Sciences. TST received compensation from Gilead Sciences as a member of the study’s Global Community Advisory and Accountability Group and funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro, outside the submitted work. SS received compensation from Gilead Sciences as a member of the study’s Global Community Advisory and Accountability Group. OO has served on the speakers’ bureau for Gilead Sciences and on advisory boards for Gilead Sciences and ViiV Healthcare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: There are over 150,000 transgender adolescents in the United States, yet research on outcomes following gender-affirming mastectomy in this age group is limited. We evaluated gender-affirming mastectomy incidence, as well as postoperative complications, including regret, in adolescents within our integrated health care system., Methods: Gender-affirming mastectomies performed from January 1, 2013 - July 31, 2020 in adolescents 12-17 years of age at the time of referral were identified. The incidence of gender-affirming mastectomy was calculated by dividing the number of patients undergoing these procedures by the number of adolescents assigned female at birth ages 12-17 within our system at the beginning of each year and amount of follow-up time within that year. Demographic information, clinical characteristics (comorbidities, mental health history, testosterone use), surgical technique, and complications, including mention of regret, of patients who underwent surgery were summarized. Patients with and without complications were compared to evaluate for differences in demographic or clinical characteristics using chi-squared tests., Results: The incidence of gender-affirming mastectomy increased 13-fold (3.7 to 47.7 per 100,000 person-years) during the study period. Of the 209 patients who underwent surgery, the median age at referral was 16 years (range 12-17) and the most common technique was double-incision (85%). For patients with greater than 1-year follow-up (n=137, 65.6%), at least one complication was found in 7.3% (n=10), which included hematoma (3.6%), infection (2.9%), hypertrophic scars requiring steroid injection (2.9%), seroma (0.7%), and suture granuloma (0.7%); 10.9 % underwent revision (n=15). There were no statistically significant differences in patient demographics and clinical characteristics between those with and without complications (p>0.05). Two patients (0.95%) had documented postoperative regret but neither underwent reversal surgery at follow-up of 3 and 7 years postoperatively., Conclusion: Between 2013-2020, we observed a marked increase in gender-affirming mastectomies in adolescents. The prevalence of surgical complications was low and of over 200 adolescents who underwent surgery, only two expressed regret, neither of which underwent a reversal operation. Our study provides useful and positive guidance for adolescent patients, their families, and providers regarding favorable outcomes with gender-affirming mastectomy., Competing Interests: Conflicts of Interests: The authors have no conflicts of interests.

Competing Interests: We declare no competing interests. JCH is supported by a grant from the National Institutes of Health (T32 DA007250).

Importance: Long-term follow-up is needed to evaluate gaps in HIV preexposure prophylaxis (PrEP) care delivery and to identify individuals at risk for falling out of care., Objective: To characterize the PrEP continuum of care, including prescription, initiation, discontinuation, and reinitiation, and evaluate incident HIV infections., Design, Setting, and Participants: This retrospective cohort study used data from the electronic health records (EHR) at Kaiser Permanente Northern California to identify individuals aged 18 years and older who received PrEP care between July 2012 and March 2019. Individuals were followed up from date of linkage (defined as a PrEP referral or PrEP-coded encounter) until March 2019, HIV diagnosis, discontinuation of health plan membership, or death. Data were analyzed from December 2019 to January 2021., Exposures: Sociodemographic factors included age, sex, race and ethnicity, and neighborhood deprivation index, and clinical characteristics were extracted from the EHR., Main Outcomes and Measures: The primary outcomes were attrition at each step of the PrEP continuum of care and incident HIV infections., Results: Among 13 906 individuals linked to PrEP care, the median (interquartile range [IQR]) age was 33 (27-43) years, 6771 individuals (48.7%) were White, and 13 227 (95.1%) were men. Total follow-up was 26 210 person-years (median [IQR], 1.6 [0.7-2.8] years). Of individuals linked to PrEP care, 88.1% (95% CI, 86.1%-89.9%) were prescribed PrEP and of these, 98.2% (95% CI, 97.2%-98.8%) initiated PrEP. After PrEP initiation, 52.2% (95% CI, 48.9%-55.7%) discontinued PrEP at least once during the study period, and 60.2% (95% CI, 52.2%-68.3%) of these individuals subsequently reinitiated. Compared with individuals aged 18 to 25 years, older individuals were more likely to receive a PrEP prescription (eg, age >45 years: hazard ratio [HR], 1.21 [95% CI, 1.14-1.29]) and initiate PrEP (eg, age >45 years: HR, 1.09 [95% CI, 1.02-1.16]) and less likely to discontinue (eg, age >45 years: HR, 0.46 [95% CI, 0.42-0.52]). Compared with White patients, African American and Latinx individuals were less likely to receive a PrEP prescription (African American: HR, 0.74 [95% CI, 0.69-0.81]; Latinx: HR, 0.88 [95% CI, 0.84-0.93]) and initiate PrEP (African American: HR, 0.87 [95% CI, 0.80-0.95]; Latinx: HR, 0.90 [95% CI, 0.86-0.95]) and more likely to discontinue (African American: HR, 1.36 [95% CI, 1.17-1.57]; Latinx: 1.33 [95% CI, 1.22-1.46]). Similarly, women, individuals with lower neighborhood-level socioeconomic status (SES), and persons with a substance use disorder (SUD) were less likely to be prescribed (women: HR, 0.56 [95% CI, 0.50-0.62]; lowest SES: HR, 0.72 [95% CI, 0.68-0.76]; SUD: HR, 0.88 [95% CI, 0.82-0.94]) and initiate PrEP (women: HR, 0.71 [95% CI, 0.64-0.80]; lower SES: HR, 0.93 [95% CI, 0.87-.0.99]; SUD: HR, 0.88 [95% CI, 0.81-0.95]) and more likely to discontinue (women: HR, 1.99 [95% CI, 1.67-2.38]); lower SES: HR, 1.40 [95% CI, 1.26-1.57]; SUD: HR, 1.23 [95% CI, 1.09-1.39]). HIV incidence was highest among individuals who discontinued PrEP and did not reinitiate PrEP (1.28 [95% CI, 0.93-1.76] infections per 100 person-years)., Conclusions and Relevance: These findings suggest that gaps in the PrEP care continuum were concentrated in populations disproportionately impacted by HIV, including African American individuals, Latinx individuals, young adults (aged 18-25 years), and individuals with SUD. Comprehensive strategies to improve PrEP continuum outcomes are needed to maximize PrEP impact and equity.

Background: Obesity can often be a barrier to gender-affirming top surgery in transmasculine patients because of concern for increased surgical site complications., Study Design: All adult patients (N = 948) within an integrated health care system who underwent gender-affirming mastectomy from 2013 to 2018 were retrospectively reviewed to evaluate the relationship between obesity and surgical site complications or revisions., Results: One third of patients (n = 295) had obese body mass index (BMI), and those patients were further stratified into obesity class I (BMI of 30-34.9 kg/m2, 9.4%), class II (BMI of 35-39.9 kg/m2, 8.9%), and class III (BMI of ≥40 kg/m2, 2.9%). A majority of patients across BMI categories underwent double incision surgery. There were no significant differences in complications or revisions between patients with obesity versus those with normal BMI, when BMI was treated as a categorical or continuous variable and when evaluating only patients who underwent double incision surgery., Conclusions: Obesity alone should not be considered a contraindication for gender-affirming mastectomy. Attention should be given to several modifiable risk factors identified in this study, including lesser incision surgical techniques, tobacco use, and testosterone use. Further research is needed to understand risks associated with the highest BMI (≥40 kg/m2) patients and to assess patient satisfaction with surgical outcome., Competing Interests: Conflicts of interest and sources of funding: The authors have no financial disclosures., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aimed to pilot systematic gender identity screening during adolescent well checks and examine perceptions of feasibility and acceptability of screening from adolescents, parents/guardians, and clinicians., Methods: Adolescents aged 12-18 years with a well visit between July 1, 2018, and June 30, 2019 (n = 134,114; 817 pilot and 133,297 usual care) in Kaiser Permanente Northern California (KPNC) pediatric primary care clinics. "What is your gender?" was added to the previsit questionnaire in pilot clinics; all other KPNC clinics provided usual care. Additional anonymous surveys were administered to adolescents and parents/guardians in the pilot clinics and to all KPNC pediatric clinicians. Multivariable logistic regression examined associations between clinics and patients reporting as transgender and gender diverse (TGD). Descriptive statistics summarized patient, parent/guardian, and clinician perceptions of gender identity screening., Results: Adjusting for age and race/ethnicity, adolescents had higher odds of reporting as TGD in pilot clinics than in usual care (odds ratio = 6.91, 95% confidence interval = 3.76-12.74). Two thirds of adolescents, 75.5% of parents/guardians, and 92.5% of clinicians felt it was important to screen for gender identity in primary care. Less than 2% of adolescents found the question confusing, offensive, or uncomfortable, and 2.8% of parents/guardians felt it was offensive. In addition, 36.4% of clinicians and 3.6% of parents/guardians were concerned it would affect visit workflow/time., Conclusions: Most adolescents, parents/guardians, and pediatric clinicians viewed systematic gender identity screening as both feasible and acceptable. Standardized gender identity screening during adolescent well checks could facilitate and increase identification of TGD adolescents and the delivery of gender-affirming care for adolescents and families in need., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The pre-exposure prophylaxis (PrEP) cascade outlines sequential steps to maximize PrEP's impact and highlights potential intervention targets to improve PrEP implementation. We evaluate the PrEP cascade in the Together 5000 study (T5K)., Methods: T5K is an internet-based, US national cohort study of PrEP-eligible men and trans persons who have sex with men who were not taking PrEP at enrollment. Using longitudinal data from baseline (2017-2018) and year 1 follow-up (2018-2019, n = 4229), we evaluated 5 steps of the PrEP cascade-PrEP contemplation: believes they are a good candidate for PrEP; PrEParation: plans to initiate PrEP; PrEP action: speaks to a provider about PrEP; PrEP initiation: receives a prescription for PrEP; and PrEP maintenance: continues to take PrEP. We compared the cascade across geographic region and identified factors associated with gaps in the cascade., Results: After 1 year, 1092 (26%) participants had initiated PrEP, 709 (17%) were still using PrEP, and 177 (4%) were no longer clinically indicated for PrEP. Participants in the South and Midwest were less likely to speak to a provider about PrEP or initiate PrEP. Baseline characteristics associated with lower odds of PrEP initiation at year 1 include: not having a college degree; earning <$20,000/year; not having health insurance; having very low food security; and not having a primary care doctor., Conclusions: Lack of health care access is a major barrier to PrEP implementation and may exacerbate disparities in PrEP uptake across geographic regions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare risk of dementia after age 50 by HIV status among individuals in a primary care setting., Design: Observational cohort study; participants were identified from 2013 to 2017 and followed through 2019., Methods: Participants were people with HIV (PWH) on antiretroviral therapy (ART) and demographically similar people without HIV (PWOH), all at least 50 years old and with no prior diagnosis of dementia. The study setting was Kaiser Permanente Northern California, an integrated healthcare delivery system in the United States. Incident dementia diagnoses and baseline data on sociodemographics, smoking, alcohol use, other substance use, and clinical factors were gathered from the electronic health record. Cumulative proportion of incident dementia by HIV status was assessed using Kaplan--Meier curves. Unadjusted and adjusted hazard ratios for incident dementia by HIV status were generated using Cox proportional hazards models with age as the time scale., Results: The study included 5381 PWH and 119 022 PWOH (average age at baseline: 57 and 58 years, respectively). Incident dementia was diagnosed in 117 PWH and 2427 PWOH. By age 80, 25.8% of PWH and 13.8% of PWOH had been diagnosed with dementia, corresponding with an unadjusted hazard ratio of 1.98 (95% CI 1.64-2.39). After adjustment for sociodemographic, substance use, and clinical factors, including frequency of outpatient visits, the risk of dementia among PWH remained elevated (vs. PWOH, adjusted hazard ratio = 1.58, 95% CI 1.31-1.92)., Conclusion: Compared with PWOH, PWH were at 58% higher risk for dementia despite HIV treatment with ART. Research is needed to investigate the potential benefits of targeted risk factor management or earlier cognitive screening in this population., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Smoking tobacco and unhealthy alcohol use may negatively influence HIV care continuum outcomes but have not been examined in combination., Methods: Participants were people with HIV (PWH) in Kaiser Permanente Northern California. Predictors included smoking status and unhealthy alcohol use (exceeding daily and/or weekly limits) reported by patients during primary care screening (index date). Outcomes were based on not achieving the following steps in the care continuum: linkage to HIV care (≥1 visit within 90 days of newly identified HIV diagnosis), retention (2+ in-person visits, 60+ days apart) and HIV RNA control (<75 copies/mL). Adjusted odds ratios (ORs) were obtained from separate logistic regression models for each outcome associated with smoking and unhealthy alcohol use independently and combined., Results: The overall sample (N = 8958) had a mean age of 48.0 years; was 91.3 % male; 54.0 % white, 17.6 % Latino, 15.1 % black, and 9.6 % other race/ethnicity. Smoking was associated with higher odds of not being linked to HIV care (OR = 1.60 [95 % CI 1.03-2.48]), not retained (OR = 1.30 [95 % CI 1.13-1.50]), and HIV RNA not in control (OR = 1.91 [95 % CI 1.60-2.27]). Alcohol measures were not independently associated with outcomes. The combination of unhealthy alcohol use and smoking (versus neither) was associated with higher odds of not being linked to care (OR = 2.83 [95 % CI 1.40-5.71]), although the interaction did not reach significance (p = 0.18)., Conclusions: In this large sample of PWH in an integrated health care system, smoking, both independently and in combination with unhealthy alcohol use, was associated with worse HIV care continuum outcomes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study examined the demographic and clinical correlates of HIV stigma and evaluated how HIV stigma was associated with physical and mental health outcomes one year later in a primary-care based cohort of persons living with HIV (PLHIV; N = 584). HIV stigma was measured using a modified Berger HIV stigma scale, which includes four subscales: (1) personalized stigma; (2) disclosure concerns; (3) negative self-image; and (4) concerns around public attitudes towards PLHIV. Physical and mental health were assessed using the 12-item short form survey (SF-12). Compared to whites, African Americans were more likely to have higher personalized stigma scores (adjusted prevalence ratio [aPR] 1.54 [95% confidence interval 1.10-2.15]), disclosure concerns (aPR 1.40 [1.03-1.92]), and concerns with public attitudes about PLHIV (aPR 1.61 [1.11-2.34]). Hispanic/Latinx participants were more likely to have concerns around public attitudes towards PLHIV (aPR 1.50 [1.11-2.02]) than whites. Compared to men, women were more likely to have higher negative self-image scores (aPR 1.50 [1.08-2.08]). Higher stigma scores were associated with poorer subsequent self-reported physical and mental health functional status. Our findings highlight the substantial need for addressing HIV stigma, particularly among minority subgroups.

Among 279 patients within a large healthcare system in San Francisco, event-driven HIV pre-exposure prophylaxis using a 2-1-1 regimen was a desirable alternative to daily dosing. Problems with adherence, planning sex in advance, or side effects were infrequent (13.9%). We found no new HIV infections over 136 person-years of follow-up., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The objective was to describe levels and predictors of knowledge, attitudes, and willingness to prescribe pre-exposure prophylaxis (PrEP) among Brazilian Infectious Disease (ID) Physicians. The design was a cross-sectional study. We collected information on demographics and attitudes/knowledge about PrEP using an anonymous electronic survey. Willingness to prescribe PrEP, fear of adherence issues, and concerns about risk compensation were addressed in three case vignettes that varied by a single characteristic (i.e., by gender identity, drug use, and socioeconomic status) randomly assigned to physicians. Three hundred seventy ID physicians responded to the survey. Although most identified as informed/well informed about PrEP (75%) and believed PrEP availability to be necessary (38%), concerns with adherence (49%), side effects (38%), risk compensation (28%), and increase in sexually transmitted infection incidence (38%) were raised. We found no statistically significant differences in willingness to prescribe PrEP and concerns around risk compensation across the three case vignettes. ID physicians who declared having a religion reported more concerns about risk compensation compared to those self-identified as atheists (72% vs. 46%, p  < .001). Most Brazilian ID physicians reported a positive attitude toward PrEP. Patients' gender identity, drug use, and socioeconomic status were not associated with willingness to prescribe PrEP. However, ID physicians who declared having a religion were more frequently concerned about risk compensation among PrEP users, suggesting that personal beliefs can influence PrEP implementation.

In a sample of people with HIV (PWH) enrolled in an alcohol intervention trial and followed for 12 months, we examined the association of changes in days (i.e., decrease, increase, no change [reference]) of unhealthy drinking (consuming ≥ 4/≥ 5 drinks for women/men) with antiretroviral therapy adherence (≥ 95% adherent), viral suppression (HIV RNA < 75 copies/mL), condomless sex with HIV-negative/unknown status partners, and dual-risk outcome (HIV RNA ≥ 75 copies/mL plus condomless sex). The sample included 566 PWH (96.8% male; 63.1% White; 93.9% HIV RNA < 75 copies/mL) who completed baseline, 6-, and 12-month assessments. Decrease in days of unhealthy drinking was associated with increased likelihood of viral suppression (odds ratio [OR] 3.78; 95% confidence interval [CI] 1.06, 13.51, P = .04) versus no change. Increase in days of unhealthy drinking was associated with increased likelihood of condomless sex (OR 3.13; 95% CI 1.60, 6.12, P < .001). Neither increase nor decrease were associated with adherence or dual-risk outcome. On a continuous scale, for each increase by 1 day of unhealthy drinking in the prior month, the odds of being 95% adherent decreased by 6% (OR 0.94, 95% CI 0.88, 1.00, P = 0.04).

Objectives: People with HIV (PWH) have a high burden of bacterial sexually transmitted infections (STIs). We examined the relationship of alcohol and drug use and partner pre-exposure prophylaxis (PrEP) use to STI prevalence in a cohort of PWH with a history of unhealthy alcohol use., Methods: We analysed data from a primary care-based alcohol intervention study at Kaiser Permanente Northern California (KPNC). Participants were recruited between April 2013 and May 2015 and were followed for up to 24 months. We linked participant responses to questions from the 24 month follow-up interview, including alcohol and drug use and partner PrEP use, with STI test results (ie, syphilis, chlamydia, gonorrhoea) in the KPNC electronic health record. Prevalence ratios (PR) were estimated using Poisson models fitted with robust variance estimators to evaluate the association of substance use and partner use of PrEP with STIs., Results: In the analytic sample (n=465), the median age was 52 years (IQR 45-59); 67% were white; 95% were men who have sex with men. Thirty-two per cent of participants had HIV-positive partners only; 31% had HIV-negative partners with at least one on PrEP in the previous year and 37% had HIV-negative partners without any on PrEP. Twenty-three per cent reported alcohol and drug use prior to sex in the last 6 months. Eight per cent of participants had an STI. Partner PrEP use (adjusted PR (aPR) 2.99 (95% CI 1.11 to 8.08)) was independently associated with higher STI prevalence. Participants who reported use of alcohol (aPR 1.53 (0.61 to 3.83)), drugs (aPR 1.97 (0.71 to 5.51)) or both (aPR 1.93 (0.75 to 4.97)) prior to sex had a higher STI prevalence., Conclusions: The higher prevalence of STIs among PWH with unhealthy alcohol use who have partners on PrEP suggests that this subgroup may be a high-yield focus for targeted outreach, STI screening and sexual health counselling., Competing Interests: Competing interests: JM has received research grant support from Merck and has consulted on a research grant to Kaiser Permanente Northern California from Gilead Sciences. All other authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We characterized referral trends over time at a transgender clinic within an integrated health system in Northern California. We identified the transition-related requests of pediatric transgender and gender-nonconforming patients and evaluated differences in referrals by age group., Methods: Medical records were analyzed for all patients <18 years of age in the Kaiser Permanente Northern California health system who were referred to a specialty transgender clinic between February 2015 and June 2018. Trends in treatment demand, demographic data, service requests, and surgical history were abstracted from medical charts and analyzed by using descriptive statistics., Results: We identified 417 unique transgender and gender-nonconforming pediatric patients. The median age at time of referral was 15 years (range 3-17). Most (62%) identified on the masculine spectrum. Of the 203 patients with available ethnicity data, 68% were non-Hispanic. During the study period, the clinic received a total of 506 referrals with a significant increase over time ( P < .001). Most referrals were for requests to start cross-sex hormones and/or blockers (34%), gender-affirming surgery (32%), and mental health (27%). Transition-related requests varied by age group: younger patients sought more mental health services, and older patients sought hormonal and surgical services. Eighty-nine patients underwent gender-affirming surgeries, mostly before age 18 and most frequently mastectomies (77%)., Conclusions: The increase in referrals supports the need for expanded and accessible health care services for this population. The transition-related care of patients in this large sample varied by age group, underscoring the need for an individualized approach to gender-affirming care., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Background: Concomitant use of cocaine and HIV pre-exposure prophylaxis (PrEP) raises important clinical questions around adherence, retention in care, and renal toxicity., Methods: We assessed the associations of confirmed cocaine use with PrEP adherence (both ascertained through objective measures), care engagement, and renal function in the iPrEx open-label extension. Cocaine use was measured in scalp hair samples and categorized as light (500-3000 pg/mg) and moderate to heavy (>3000 pg/mg). PrEP adherence in the first 3 months was measured through plasma tenofovir concentrations. Disengagement from PrEP care was defined as a gap in follow-up greater than 4 months. Serum creatinine was assessed at baseline and quarterly visits., Results: Of the 400 participants included in this analysis, 90% were men who have sex with men, 10% transgender women, 74% Hispanic/Latino; 21% tested positive for cocaine use in the last 3 months. In adjusted analysis, light cocaine use [adjusted odds ratio 2.10 (95% confidence interval: 1.07 to 4.14)] and moderate to heavy use [adjusted odds ratio 2.32 (1.08 to 5.00)] were associated with greater odds of having plasma tenofovir concentrations below the level of quantitation. Participants with moderate to heavy use had a nearly 3-fold higher rate of disengagement from PrEP care compared with nonusers (adjusted hazard ratio 2.90 [1.48 to 5.66]). We found no statistically or clinically significant differences in creatinine clearance and serum creatinine between participants who tested positive for cocaine and those who did not., Conclusions: Cocaine use decreases PrEP adherence and care engagement. Comprehensive approaches are needed to reduce cocaine use and enhance engagement along the PrEP care continuum.

In a community-based clinic serving men who have sex with men in San Francisco, California, this study characterized key steps of the pre-exposure prophylaxis (PrEP) cascade and identified correlates of retention in care. In total, 344 patients were evaluated for PrEP. Three-fourths (78%) of those who sought PrEP services initiated PrEP. The overall cumulative incidence of discontinuing PrEP at 13 months was 38%. Men with a sexually transmitted infection (STI) were 44% less likely to be retained (adjusted hazard ratio [aHR] 0.56, 95% confidence interval [0.33-0.95]). Comprehensive retention efforts for men with STIs are crucial to optimize the benefits of PrEP.

HIV pre-exposure prophyalxis (PrEP) might lead individuals to view serodisclosure as unnecessary. We examined the prevalence of non-disclosure and lack of knowledge of partner status in a global cohort of men who have sex with men (MSM) and transgender women (TW) enrolled in the iPrEx Open Label Extension (OLE). We calculated prevalence ratios by fitting a logistic model and estimating predicted probabilities using marginal standardization. Prevalence of non-disclosure and lack of knowledge of partner status were highest in Thailand (73% and 74%, respectively) and lowest in the USA (23% and 37%, respectively). In adjusted analyses, PrEP use was not significantly associated with non-disclosure or lack of knowledge of partner status (p-values>0.05). We found that relationship characteristics were significantly associated with both outcomes. Non-disclosure was higher among casual (adjusted prevalence ratio [aPR] 1.54, [95% confidence interval 1.24-1.84]) and transactional sex partners (aPR 2.03, [1.44-2.62]), and among partners whom participants have known only minutes or hours before their first sexual encounter (aPR 1.62, [1.33-1.92]). Similarly, participants were less likely to know the HIV status of casual partners (aPR 1.50, [1.30-1.71]), transactional sex partners (aPR 1.62, [1.30-1.95]), and those they have known for only days or weeks (aPR 1.13, [0.99-1.27]) or minutes or hours (aPR 1.27, [1.11-1.42]). Our findings underscore the role of dyadic factors in influencing serodisclosure. Comprehensive risk reduction counseling provided in conjunction with PrEP that address relationship characteristics are needed to help patients navigate discussions around HIV status.

Introduction: Stimulant and heavy alcohol use are prevalent and associated with elevated risk for HIV seroconversion among men who have sex with men (MSM) and transgender women. In addition, each can pose difficulties for antiretroviral adherence among people living with HIV. Scant research has examined the associations of stimulant and heavy alcohol use with adherence to daily oral pre-exposure prophylaxis (PrEP) among MSM and transgender women. To address this gap in the literature, we evaluated the hypothesis that stimulant use and binge drinking are prospectively associated with sub-optimal PrEP adherence., Methods: We analysed data from participants in a nested case-cohort in the iPrEx open label extension. Stimulant use (i.e. powder cocaine, crack-cocaine, cocaine paste, methamphetamine, cathinone) and binge drinking (i.e. ≥5 drinks in a single day) in the last 30 days were assessed. Baseline urine was tested for stimulants using immunoassays to reduce misclassification. Sub-optimal adherence was defined as tenofovir drug concentrations in dried blood spots less than 700 fmol per punch, indicative of less than four doses per week. We tested the prospective association of stimulant use and binge drinking with sub-optimal adherence at the 4-week follow-up visit., Results and Discussion: Data from 330 participants were analysed. The majority of the participants were MSM (89%) with a median age at baseline of 29 years (interquartile range 24 to 39). Approximately 16% (52/330) used stimulants and 22% (72/330) reported binge drinking in the last 30 days. Stimulant users had fivefold greater odds of sub-optimal PrEP adherence compared to non-users in adjusted analysis (adjusted odds ratio [aOR] 5.04; [95% CI 1.35 to 18.78]). Self-reported binge drinking was not significantly associated with sub-optimal adherence after adjusting for stimulant use and baseline confounders (aOR 1.16 [0.49 to 2.73]). Depressive symptoms, being transgender, and number of sex partners were also not significantly associated with sub-optimal PrEP adherence (p > 0.05)., Conclusions: Stimulant use is a risk factor for sub-optimal PrEP adherence in the month following PrEP initiation. Comprehensive prevention approaches that reduce stimulant use may optimize PrEP adherence. Creating adherence plans that specifically address PrEP dosing in the context of ongoing stimulant use should also be considered., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)