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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.)

Background: People with HIV (PWH) are at elevated risk for suicidal ideation (SI), yet few studies have examined how substance use, clinical and sociodemographic factors are associated with SI among PWH., Method: We used substance use (Tobacco, Alcohol, Prescription Medication, and Other Substance Use [TAPS]) and depression (PHQ-9) data from computerized screening of adult PWH in primary care clinics in Northern California, combined with health record data on psychiatric diagnoses, HIV diagnosis, treatment, and control (HIV RNA, CD4), insurance, and neighborhood deprivation index (NDI) to examine factors associated with SI (PHQ-9 item 9 score > 0). Adjusted odds ratios (aOR) for SI were obtained from logistic regression models., Results: Among 2829 PWH screened (92 % male; 56 % white; mean (SD) age of 54 (13) years; 220 (8 %) reported SI. Compared with no problematic use, SI was higher among those reporting one (aOR = 1.65, 95 % CI = 1.17, 2.33), two (aOR = 2.23, 95 % CI = 1.42, 3.49), or ≥ 3 substances (aOR = 4.49, 95 % CI = 2.41, 8.39). SI risk was higher for those with stimulant use (aOR = 3.55, 95 % CI = 2.25, 5.59), depression (aOR = 4.18, 95 % CI = 3.04, 5.74), and anxiety diagnoses (aOR = 1.67, 95 % CI = 1.19, 2.34), or Medicaid (aOR = 2.11, 95%CI = 1.24, 3.60) compared with commercial/other insurance. SI was not associated with HIV-related measures or NDI., Limitations: SI was assessed with a single PHQ-9 item. Simultaneous SI and exposure data collection restricts the ability to establish substance use as a risk factor., Conclusions: HIV care providers should consider multiple substance use, stimulant use, depression or anxiety, and public insurance as risk factors for SI and provide interventions when needed., Competing Interests: Declaration of competing interest The authors report no competing of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Management of hypertension, dyslipidemia, diabetes and other modifiable factors may mitigate the cardiovascular disease (CVD) risk in people with human immunodeficiency virus (HIV, PWH) compared with people without HIV (PWoH)., Methods: This was a retrospective cohort study of 8285 PWH and 170 517 PWoH from an integrated health system. Risk factor control was measured using a novel disease management index (DMI) accounting for amount/duration above treatment goals (0% to 100% [perfect control]), including 2 DMIs for hypertension (diastolic and systolic blood pressure), 3 for dyslipidemia (low-density lipoprotein, total cholesterol, triglycerides), and 1 for diabetes (HbA1c). CVD risk by HIV status was evaluated overall and in subgroups defined by DMIs, smoking, alcohol use, and overweight/obesity in adjusted Cox proportional hazards models., Results: PWH and PWoH had similar DMIs (80%-100%) except for triglycerides (worse for PWH) and HbA1c (better for PWH). In adjusted models, PWH had an elevated risk of CVD compared with PWoH (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.07-1.31). This association was attenuated in subgroups with controlled dyslipidemia and diabetes but remained elevated for PWH with controlled hypertension or higher total cholesterol. The strongest HIV status association with CVD was seen in the subgroup with frequent unhealthy alcohol use (HR, 2.13; 95% CI, 1.04-4.34)., Conclusions: Control of dyslipidemia and diabetes, but not hypertension, attenuated the HIV status association with CVD. The strong association of HIV and CVD with frequent unhealthy alcohol use suggests enhanced screening and treatment of alcohol problems in PWH is warranted., Competing Interests: Potential conflicts of interest. M. C. reports research grants from Gilead, MSD, and ViiV (paid to institution); payment for expert testimony from Gilead, MSD, and ViiV Healthcare (paid to institution); and support for attending meetings and/or travel from Gilead (paid to institution). C. B. H. reports grants or contracts from Gilead (payments to institution for unrelated research). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We characterized polysubstance use burden and associations with mental health problems across demographic subgroups of PWH. In 2018-2020, as part of a primary care-based intervention study, PWH in care at three medical centers in Kaiser Permanente Northern California were screened for depression (PHQ-9≥10), anxiety (GAD-2≥3), and substance use (Tobacco, Alcohol, Prescription medication, and other Substance use [TAPS]≥1 per substance). We used Poisson regression to estimate prevalence ratios (PRs) comparing polysubstance use prevalence (TAPS≥1 for ≥2 substances) between PWH with positive screens for depression or anxiety vs. neither, among all PWH, and stratified by race/ethnicity and age (restricted to men), adjusting for sociodemographics, CD4, and HIV load. Screened PWH (N = 2865) included 92% men, 56% White, 19% Black, and 15% Hispanic PWH, with a median age of 55 years. Overall, polysubstance use prevalence was 26.4% (95% CI 24.9%-28.1%). PWH with depression or anxiety (n = 515) had an adjusted polysubstance use PR of 1.26 (1.09-1.46) vs. PWH with neither (n = 2350). Adjusted PRs were 1.47 (1.11-1.96), 1.07 (0.74-1.54), and 1.10 (0.85-1.41) among Black, Hispanic, and White men, respectively. Adjusted PRs did not differ by age group. Interventions should consider jointly addressing mental health and substance use problems and potential drivers, e.g. stigma or socioeconomic factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Davy-Mendez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Since May 2022, mpox has been identified in 108 countries without endemic disease; most cases have been in gay, bisexual, or other men who have sex with men. To determine number of missed cases, we conducted 2 studies during June-September 2022: a prospective serologic survey detecting orthopoxvirus antibodies among men who have sex with men in San Francisco, California, and a retrospective monkeypox virus PCR testing of swab specimens submitted for other infectious disease testing among all patients across the United States. The serosurvey of 225 participants (median age 34 years) detected 18 (8.0%) who were orthopoxvirus IgG positive and 3 (1.3%) who were also orthopoxvirus IgM positive. The retrospective PCR study of 1,196 patients (median age 30 years; 54.8% male) detected 67 (5.6%) specimens positive for monkeypox virus. There are likely few undiagnosed cases of mpox in regions where sexual healthcare is accessible and patient and clinician awareness about mpox is increased.

Background: Mental health and substance use disorders disproportionately affect people with HIV (PWH), and may have been exacerbated during COVID-19. The Promoting Access to Care Engagement (PACE) trial was designed to assess the effectiveness of electronic screening for mental health and substance use in HIV primary care and enrolled PWH from October 2018 to July 2020. Our objective here was to compare screening rates and results for PWH before (October 2018 - February 2020) and early in the COVID-19 pandemic (March-July 2020)., Methods: Adult (≥ 18 years) PWH from 3 large HIV primary care clinics in a US-based integrated healthcare system were offered electronic screening online or via in-clinic tablet computer every 6 months. Screening completion and results (for depression, suicidal ideation, anxiety, and substance use) were analyzed using logistic regression with generalized estimating equations to estimate prevalence ratios (PR) before and after the start of the regional COVID-19 shelter-in-place orders on March 17, 2020. Models adjusted for demographics (age, sex, race/ethnicity), HIV risk factors (men who have sex with men, injection drug use, heterosexual, other), medical center, and modality of screening completion (online or tablet). We conducted qualitative interviews with providers participating in the intervention to evaluate how the pandemic impacted patient care., Results: Of 8,954 eligible visits, 3,904 completed screenings (420 during COVID, 3,484 pre-COVID), with lower overall completion rates during COVID (38% vs. 44%). Patients completing screening during COVID were more likely to be White (63% vs. 55%), male (94% vs. 90%), and MSM (80% vs., 75%). Adjusted PRs comparing COVID and pre-COVID (reference) were 0.70 (95% CI), 0.92 (95% CI), and 0.54 (95% CI) for tobacco use, any substance use, and suicidal ideation, respectively. No significant differences were found by era for depression, anxiety, alcohol, or cannabis use. These results were in contrast to provider-reported impressions of increases in substance use and mental health symptoms., Conclusion: Findings suggest PWH had modest declines in screening rates early in the COVID-19 pandemic which may have been affected by the shift to telemedicine. There was no evidence that mental health problems and substance use increased for PWH in primary care., Trial Registration: NCT03217058 (First registration date: 7/13/2017); https://clinicaltrials.gov/ct2/show/NCT03217058., (© 2023. The Author(s).)

Outcomes of PWH with unhealthy alcohol use, such as alcohol use reduction or progression to AUD, are not well-known and may differ by baseline patterns of unhealthy alcohol use. Among 1299 PWH screening positive for NIAAA-defined unhealthy alcohol use in Kaiser Permanente Northern California, 2013-2017, we compared 2-year probabilities of reduction to low-risk/no alcohol use and rates of new AUD diagnoses by baseline use patterns, categorized as exceeding: only daily limits (72% of included PWH), only weekly limits (17%), or both (11%), based on NIAAA recommendations. Overall, 73.2% (95% CI 70.5-75.9%) of re-screened PWH reduced to low-risk/no alcohol use over 2 years, and there were 3.1 (95% CI 2.5-3.8%) new AUD diagnoses per 100 person-years. Compared with PWH only exceeding daily limits at baseline, those only exceeding weekly limits and those exceeding both limits were less likely to reduce and likelier to be diagnosed with AUD during follow-up. PWH exceeding weekly drinking limits, with or without exceeding daily limits, may have a potential need for targeted interventions to address unhealthy alcohol use., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

Background: Only a few recent reports have examined longitudinal adherence patterns in US clinics and its impact on immunological and virological outcomes among large cohorts initiating contemporary antiretroviral therapy (ART) in US clinics., Methods: We followed all persons with HIV (PLWH) in a California clinic population initiating ART between 2010 and 2017. We estimated longitudinal adherence for each PLWH by calculating the medication possession ratio within multiple 6-month intervals using pharmacy refill records., Results: During the study, 2315 PWLH were followed for a median time of 210.8 weeks and only 179 (7.7%) were lost-to-follow-up. The mean adherence was 84.9%. Age (Hazard Ratio (HR): (95% confidence interval): 1.25 (1.20-1.31) per 10-year increase) and Black race (HR: 0.62 (0.53-0.73) vs. White) were associated with adherence in the cohort. A 10% percent increase in adherence increased the odds of being virally suppressed by 37% (OR and 95% CI: 1.37 [1.33-1.41]) and was associated with an increase in mean CD4 count by 8.54 cells/ul in the next 6-month interval (p-value <0.0001)., Conclusions: Our study shows that despite large improvements in retention in care, demographic disparities in adherence to ART persist. Adherence was lower among younger patients and black patients. Our study confirmed the strong association between adherence to ART and viral suppression but could only establish a weak association between adherence and CD4 count. These findings reaffirm the importance of adherence and retention in care and further highlight the need for tailored patient-centered HIV Care Models as a strategy to improve PLWH's outcomes., Competing Interests: The authors have read the journal’s policy and have the following competing interests to declare: RWS previously received a research grant from Janssen Scientific Affairs (https://www.janssen.com/). This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

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.)

Background: There are few descriptions of virologic failure (VF) and acquired drug resistance (HIVDR) in large cohorts initiating contemporary antiretroviral therapy (ART)., Methods: We studied all persons with HIV (PWH) in a California clinic population initiating ART between 2010 and 2017. VF was defined as not attaining virologic suppression, discontinuing ART, or virologic rebound prompting change in ART., Results: During the study, 2315 PWH began ART. Six companion drugs were used in 93.3% of regimens: efavirenz, elvitegravir/c, dolutegravir, b-darunavir, rilpivirine, and raltegravir. During a median follow-up of 36 months, 214 (9.2%) PWH experienced VF (2.8 per 100 person-years) and 62 (2.7%) experienced HIVDR (0.8 per 100 person-years). In multivariable analyses, younger age, lower CD4 count, higher virus load, and b-atazanavir were associated with increased VF risk; lower CD4 count, higher virus load, and nevirapine were associated with increased HIVDR risk. Compared with efavirenz, dolutegravir, raltegravir, and b-darunavir were associated with reduced HIVDR risk. Risks of VF and HIVDR were not significantly associated with ART initiation year. Of the 62 PWH with HIVDR, 42 received an non-nucleoside RT inhibitor (NNRTI), 15 an integrase-strand transfer inhibitor (INSTI), and 5 a protease inhibitor (PI). Among those with HIVDR on an NNRTI or first-generation INSTI, 59% acquired dual class resistance and 29% developed tenofovir resistance; those receiving a PI or dolutegravir developed just M184V., Conclusions: Despite the frequent use of contemporary ART regimens, VF and HIVDR continue to occur. Further efforts are required to improve long-term ART virological responses to prevent the consequences of ongoing HIV-1 replication including virus transmission and HIVDR., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Tenofovir alafenamide shows high antiviral efficacy and improved renal and bone safety compared with tenofovir disoproxil fumarate when used for HIV treatment. Here, we report primary results from a blinded phase 3 study evaluating the efficacy and safety of pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir alafenamide versus emtricitabine and tenofovir disoproxil fumarate for HIV prevention., Methods: This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in regions of Europe and North America, where there is a high incidence of HIV or prevalence of people living with HIV, or both. We enrolled adult cisgender men who have sex with men and transgender women who have sex with men, both with a high risk of acquiring HIV on the basis of their self-reported sexual behaviour in the past 12 weeks or their recent history (within 24 weeks of enrolment) of bacterial sexually transmitted infections. Participants with current or previous use of PrEP with emtricitabine and tenofovir disoproxil fumarate were not excluded. We used a computer-generated random allocation sequence to randomly assign (1:1) participants to receive either emtricitabine (200 mg) and tenofovir alafenamide (25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine (200 mg) and tenofovir disoproxil fumarate (300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). As such, all participants were given two tablets. The trial sponsor, investigators, participants, and the study staff who provided the study drugs, assessed the outcomes, and collected the data were masked to group assignment. The primary efficacy outcome was incident HIV infection, which was assessed when all participants had completed 48 weeks of follow-up and half of all participants had completed 96 weeks of follow-up. This full analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug and had at least one post-baseline HIV test. Non-inferiority of emtricitabine and tenofovir alafenamide to emtricitabine and tenofovir disoproxil fumarate was established if the upper bound of the 95·003% CI of the HIV incidence rate ratio (IRR) was less than the prespecified non-inferiority margin of 1·62. We prespecified six secondary bone mineral density and renal biomarker safety endpoints to evaluate using the safety analysis set. This analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02842086, and is no longer recruiting., Findings: Between Sept 13, 2016, and June 30, 2017, 5387 (92%) of 5857 participants were randomly assigned and received emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693). At the time of the primary efficacy analysis (ie, when all participants had completed 48 weeks and 50% had completed 96 weeks) emtricitabine and tenofovir alafenamide was non-inferior to emtricitabine and tenofovir disoproxil fumarate for HIV prevention, as the upper limit of the 95% CI of the IRR, was less than the prespecified non-inferiority margin of 1·62 (IRR 0·47 [95% CI 0·19-1·15]). After 8756 person-years of follow-up, 22 participants were diagnosed with HIV, seven participants in the emtricitabine and tenofovir alafenamide group (0·16 infections per 100 person-years [95% CI 0·06-0·33]), and 15 participants in the emtricitabine and tenofovir disoproxil fumarate group (0·34 infections per 100 person-years [0·19-0·56]). Both regimens were well tolerated, with a low number of participants reporting adverse events that led to discontinuation of the study drug (36 [1%] of 2694 participants in the emtricitabine and tenofovir alafenamide group vs 49 [2%] of 2693 participants in the emtricitabine and tenofovir disoproxil fumarate group). Emtricitabine and tenofovir alafenamide was superior to emtricitabine and tenofovir disoproxil fumarate in all six prespecified bone mineral density and renal biomarker safety endpoints., Interpretation: Daily emtricitabine and tenofovir alafenamide shows non-inferior efficacy to daily emtricitabine and tenofovir disoproxil fumarate for HIV prevention, and the number of adverse events for both regimens was low. Emtricitabine and tenofovir alafenamide had more favourable effects on bone mineral density and biomarkers of renal safety than emtricitabine and tenofovir disoproxil fumarate., Funding: Gilead Sciences., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.)

Background: Unhealthy alcohol use has adverse effects on HIV treatment. Screening, brief intervention, and referral to treatment (SBIRT) has some evidence of efficacy but may not be sufficient for those with low motivation or comorbid substance use., Objective: To examine the effectiveness of motivational interviewing (MI) and emailed feedback (EF) among primary care HIV-positive patients, compared with treatment as usual care (UC) only, which included SBIRT., Design: Randomized clinical trial., Participants: Six hundred fourteen adult HIV-positive patients in Kaiser Permanente Northern California who reported prior-year unhealthy alcohol use., Intervention: Participants were randomized to either three sessions of MI (one in person and two by phone), information regarding alcohol risks via EF through a patient portal, or UC alone. MI and EF participants who reported unhealthy alcohol use at 6 months were offered additional MI and EF treatment, respectively., Main Measures: Participant-reported unhealthy alcohol use (defined as ≥ 4/≥ 5 drinks per day for women/men), alcohol problems at 12 months, based on blinded telephone interviews. Secondary outcomes included drug use and antiretroviral (ART) adherence., Key Results: At 12 months, there were no overall group differences, but in all three arms, there were declines in unhealthy alcohol use and alcohol-related problems (p < 0.001). Participants reporting low motivation to reduce drinking at baseline were less likely to report unhealthy alcohol use if they received MI vs. EF and UC (p = 0.013). At 6 months, reported illegal drug use/misuse of prescription drugs other than marijuana was lower in the MI arm than EF or UC (p = 0.012). There were no differences in ART adherence between groups., Conclusions: In a randomized trial of HIV-positive patients using two behavioral interventions compared with SBIRT alone, participants in all three conditions reduced unhealthy alcohol use. MI may provide added benefit for patients with low motivation or who report illegal drug use/misuse of prescription drugs., Trial Registration: NCT01671501 ( ClinicalTrials.gov ).

Background: Substance use disorders (SUDs) and psychiatric disorders are common among people with HIV (PWH) and lead to poor outcomes. Yet these conditions often go unrecognized and untreated in primary care., Methods: The Promoting Access to Care Engagement (PACE) trial currently in process examines the impact of self-administered electronic screening for SUD risk, depression and anxiety in three large Kaiser Permanente Northern California primary care clinics serving over 5000 PWH. Screening uses validated measures (Tobacco, Alcohol, Prescription medication, and other Substance use [TAPS]; and the Adult Outcomes Questionnaire [AOQ], which includes the Patient Health Questionnaire [PHQ-9] and Generalized Anxiety Disorder [GAD-2]) delivered via three modalities (secure messaging, tablets in waiting rooms, and desktop computers in exam rooms). Results are integrated automatically into the electronic health record. Based on screening results and physician referrals, behavioral health specialists embedded in primary care initiate motivational interviewing- and cognitive behavioral therapy-based brief treatment and link patients to addiction and psychiatry clinics as needed. Analyses examine implementation (screening and treatment rates) and effectiveness (SUD, depression and anxiety symptoms; HIV viral control) outcomes using a stepped-wedge design, with a 12-month intervention phase implemented sequentially in the clinics, and a 24-month usual care period prior to implementation in each clinic functioning as sequential observational phases for comparison. We also evaluate screening and treatment costs and implementation barriers and facilitators., Discussion: The study examines innovative, technology-facilitated strategies for improving assessment and treatment in primary care. Results may help to inform substance use, mental health, and HIV services., Trial Registration: NCT03217058., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Limited primary care-based research has examined hazardous drinking risk factors and motivation to reduce use in persons with HIV (PWH)., Methods: We computed prevalence ratios (PR) for factors associated with recent (<30 days) hazardous alcohol use (i.e., 4+/5+ drinks in a single day for women/men), elevated Alcohol Use Disorders Identification Test (AUDIT) scores, and importance and confidence (1-10 Likert scales) to reduce drinking among PWH in primary care., Results: Of 614 participants, 48% reported recent hazardous drinking and 12% reported high alcohol use severity (i.e., AUDIT zone 3 or higher). Factors associated with greater alcohol severity included moderate/severe anxiety (PR: 2.07; 95% CI: 1.18, 3.63), tobacco use (PR: 1.79; 1.11, 2.88), and other substance use (PR: 1.72; 1.04, 2.83). Factors associated with lower alcohol severity included age 50-59 years (PR: 0.46; 0.22, 2.00) compared with age 20-39 years, and having some college/college degree (PR: 0.61; 0.38, 0.97) compared with ≤high school. Factors associated with greater importance to reduce drinking (scores >5) included: moderate/severe depression (PR: 1.43; 1.03, 2.00) and other substance use (PR: 1.49; 1.11, 2.01). Lower importance was associated with incomes above $50,000 (PR: 0.65; 0.46, 0.91) and marijuana use (PR: 0.65; 0.49, 0.87). HIV-specific factors (e.g., CD4 and HIV RNA levels) were not associated with alcohol outcomes., Conclusions: This study identified modifiable participant characteristics associated with alcohol outcomes in PWH, including anxiety and depression severity, tobacco use, and other substance use., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: The goal of this pharmacist-led study was to utilize two validated instruments, Beers Criteria and Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP), to assess potentially inappropriate prescribing (PIP) in older patients infected with the human immunodeficiency virus (HIV) and evaluate pharmacist interventions., Design: Prospective randomized interventional trial., Setting: Large urban clinic providing interdisciplinary primary and HIV care for ~2700 HIV-positive publicly insured patients., Data Source: A computerized electronic record search was conducted for all patients who met the two search criteria: 50 years and older, and a primary care appointment within the last 12 months., Patients: After identification of 857 patients meeting the search criteria, 324 patients were randomly selected and contacted, resulting in 248 patients assessed., Measurements and Main Results: Patients had a mean age of 58 years, 71% male, 44% white, and a mean CD4 count of 536 cells/mm 3 . Common comorbidities included hypertension (56%), depression (52%), asthma/chronic obstructive pulmonary disease (48%), dyslipidemia (39%), coronary artery disease (27%), and diabetes (22%). Patients sampled were prescribed a mean of 11.6 ± 5.7 concomitant medications (excluding antiretrovirals) with 35% receiving at least 16 medications. PIP was identified in 54% and 63% of patients using the STOPP and Beers Criteria, respectively. Twenty-five contraindicated drug interactions were identified in 20 patients. After the pharmacist visit, at least 69% of patients had at least one medication discontinued with almost 10% having six or more medications discontinued. More than 40% of patients had at least one Beers or STOPP criteria that required immediate correction by the pharmacist., Conclusions: Results suggest that targeting individuals with 11 or more chronic medications would have the highest yield and greatest impact. Pharmacist-led review of medication prescribing using Beers and STOPP criteria revealed a large number of PIP, many amenable to immediate clinical pharmacist intervention., (© 2017 Pharmacotherapy Publications, Inc.)

Objectives: To perform geriatric assessments in older HIV-infected adults in San Francisco and examine the association with age and the Veterans Aging Cohort Study (VACS) index scores., Methods: A cross-sectional study was conducted from 2012 to 2014 among HIV-infected patients ≥50 years at 2 San Francisco-based HIV clinics. We evaluated 4 health domains: (1) physical health and function (activities of daily living), instrumental activities of daily living (IADL), falls, gait speed, (2) social support (physical and perceived support, loneliness), (3) mental health (depression, anxiety, posttraumatic stress disorder) and cognition, and (4) behavioral and general health (antiretroviral adherence and quality of life). Contingency table and rank-sum analyses examined associations between these domains with age and VACS index scores., Results: Three hundred fifty-nine patients completed assessments (median age 57; 85% male; 57% white; 72% >high school education). On functional assessment, 39% reported dependence with ≥1 IADL, and 40% reported falls in the previous year. Fifty-eight percent experienced loneliness, 60% the lowest levels of perceived social support, 55% depression, and 12% posttraumatic stress disorder. Forty percent had possible mild cognitive impairment. Thirty percent reported poor or fair quality of life. Older age was associated with lower CD4 counts, balance problems, slower gait, lower anxiety, poorer general health, and higher antiretroviral adherence. VACS Index score was associated with dependence in ≥1 IADL and antiretroviral adherence., Conclusion: In a large sample of older HIV-infected adults, multiple significant aging-related conditions were identified. Integrating geriatric assessment tools into HIV/AIDS clinical care may help target interventions to optimize clinical care and quality of life for older HIV-infected individuals.

The past 3 years have marked a transition from research establishing the safety and efficacy of HIV preexposure prophylaxis (PrEP) to questions about how to optimize its implementation. Until recently, PrEP was primarily offered as part of randomized controlled trials or open-label studies. These studies highlighted the key components of PrEP delivery, including regular testing for HIV and other sexually transmitted infections (STIs), adherence and risk-reduction support, and monitoring for renal toxicity. PrEP is now increasingly provided in routine clinical settings. This review summarizes models for PrEP implementation from screening through initiation and follow-up, focusing on the strengths and weaknesses of three delivery systems: a health maintenance organization, an STI clinic, and a primary care practice. These early implementation experiences demonstrate that PrEP can be successfully delivered across a variety of settings and highlight strategies to streamline PrEP delivery in clinical practice.

Referrals for and initiation of preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection increased dramatically in a large clinical practice setting since 2012. Despite high rates of sexually transmitted infections among PrEP users and reported decreases in condom use in a subset, there were no new HIV infections in this population., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

We sought to understand patient perceptions of the emergency department/urgent care (ED/UC) HIV diagnosis experience as well as factors that may promote or discourage linkage to HIV care. We conducted in-depth interviews with patients (n=24) whose HIV infection was diagnosed in the ED/UC of a public hospital in San Francisco at least six months prior and who linked to HIV care at the hospital HIV clinic. Key diagnosis experience themes included physical discomfort and limited functionality, presence of comorbid diagnoses, a wide spectrum of HIV risk perception, and feelings of isolation and anxiety. Patients diagnosed with HIV in the ED/UC may not have their desired emotional supports with them, either because they are alone or they are with family members or friends to whom they do not want to immediately disclose. Other patients may have no one they can rely on for immediate support. Nearly all participants described compassionate disclosure of test results by ED/UC providers, although several noted logistical issues that complicated the disclosure experience. Key linkage to care themes included the importance of continuity between the testing site and HIV care, hospital admission as an opportunity for support and HIV education, and thoughtful matching by linkage staff to a primary care provider. ED/UC clinicians and testing programs should be sensitive to the unique roles of sickness, risk perception, and isolation in the ED/UC diagnosis experience, as these things may delay acceptance of HIV diagnosis. The disclosure and linkage to care experience is crucial in forming patient attitudes towards HIV and HIV care, thus staff involved in disclosure and linkage activities should be trained to deliver compassionate, informed, and thoughtful care that bridges HIV testing and treatment sites.

Objective: To describe the prevalence and location of new and acute HIV diagnoses in a large urban medical center. Secondary objectives were to evaluate rapid HIV test performance, the added yield of acute HIV screening, and linkage-to-care outcomes., Design: Cross-sectional study from November 1, 2008, to April 30, 2009., Methods: The hospital laboratory performed round-the-clock rapid HIV antibody testing on venipuncture specimens from patients undergoing HIV testing in hospital and community clinics, inpatient settings, and the emergency department (ED). For patients with negative results, a public health laboratory conducted pooled HIV RNA testing for acute HIV infection. The laboratories communicated positive results from the hospital campus to a linkage team. Linkage was defined as 1 outpatient HIV-related visit., Results: Among 7927 patients, 8550 rapid tests resulted in 137 cases of HIV infection [1.7%, 95% confidence interval (CI): 1.5% to 2.0%], of whom 46 were new HIV diagnoses (0.58%, 95% CI: 0.43% to 0.77%). Pooled HIV RNA testing of 6704 specimens (78.4%) resulted in 3 cases of acute HIV infection (0.05%, 95% CI: 0.01% to 0.14%) and increased HIV case detection by 3.5%. Half of new HIV diagnoses and two thirds of acute infections were detected in the ED and urgent care clinic. Rapid test sensitivity was 98.9% (95% CI: 93.8% to 99.8%) and the specificity 99.9% (95% CI: 99.7% to 99.9%). More than 95% of newly diagnosed and out-of-care HIV-infected patients were linked to care., Conclusions: Patients undergoing HIV testing in EDs and urgent care clinics may benefit from being simultaneously screened for acute HIV infection.

Background: On 1 January 2010, a large, publicly funded clinic in San Francisco announced a "universal ART" approach to initiate antiretroviral therapy (ART) in all human immunodeficiency virus (HIV)-infected persons. The effect of changing guidance on real-world patient outcomes has not been evaluated., Methods: We evaluated untreated adult patients (defined as going >90 days without ART use) visiting clinic from 2001 to 2011. The cumulative incidence of HIV RNA suppression (viral load, <500 copies/mL), stratified by CD4 cell count at entry and calendar dates representing guideline issuance, were estimated using a competing risk framework. A multivariate Poisson-based model identified factors associated with HIV RNA suppression 6 months after clinic entry., Results: Of 2245 adults, 87% were male, and the median age was 39 years (interquartile range, 33-45 years). In 534 patients entering clinic with a CD4 cell count of >500 cells/µL, the 1-year incidence of HIV RNA suppression was 10.1% (95% confidence interval [CI], 6.6%-14.6%) before 4 April 2005; 9.1% (95% CI, 3.6%-17.4%) from 4 April 2005 to 1 December 2007; 14.1% (95% CI, 7.5%-22.8%) from 1 December 2007 to the universal ART recommendation and 52.8% (95% CI, 38.2%-65.4%) after. After adjustment, the SFGH policy was associated with a 6-fold increase in the probability of HIV RNA suppression 6 months after clinic entry., Conclusions: Recommendations to initiate ART in all HIV-infected patients increased the rate of HIV RNA suppression for patients enrolling in care with a CD4 cell count of >500 cells/µL and may foreshadow national trends given the March 2012 revision of national treatment guidelines to favor ART initiation for persons with CD4 cell counts of >500 cells/µL.

Background: HIV-infected men who have sex with men (MSM) are at increased risk of viral hepatitis because of similar behavioral risk factors for acquisition of these infections. Our objective was to estimate adherence to HIV management guidelines that recommend screening HIV-infected persons for hepatitis A, B, and C infection, and vaccinating for hepatitis A and B if susceptible., Methods: We evaluated hepatitis prevention services received by a random sample of HIV-infected MSM in 8 HIV clinics in 6 US cities. We abstracted medical records of all visits made by the patients to the clinic during the period from 2004 to 2007, to estimate hepatitis screening and vaccination rates overall and by clinic site., Results: Medical records of 1329 patients who had 14,831 visits from 2004 to 2006 were abstracted. Screening rates for hepatitis A, B, and C were 47%, 52%, and 54%, respectively. Among patients who were screened and found to be susceptible, 29% were vaccinated for hepatitis A and 25% for hepatitis B. The percentage of patients screened and vaccinated varied significantly by clinic., Conclusions: Awareness of hepatitis susceptibility and hepatitis coinfection status in HIV-infected patients is essential for optimal clinical management. Despite recommendations for hepatitis screening and vaccination of HIV-infected MSM, rates were suboptimal at all clinic sites. These low rates highlight the importance of routine review of adherence to recommended clinical services. Such reviews can prompt the development and implementation of simple and sustainable interventions to improve the quality of care.

Methamphetamine use is associated with adverse health outcomes and HIV incidence. Few studies have assessed methamphetamine use, sexual behavior and Internet use among HIV-infected patients. Surveys were administered to a sample of HIV-infected patients seeking medical care in a San Francisco county hospital and university-based clinic. In 2008, 35% of homosexual participants, 26% of heterosexual participants and 11% of female participants reported methamphetamine use in the past year. Of participants, 29% reported using the Internet to find sex partners; Internet-users versus non-Internet-users reported a higher median number of sex partners in 6 months (4 vs. 1), were more likely to report unprotected sex (32 vs. 10%), and higher rates of methamphetamine use in the past 12 months (48 vs. 24%). Given the association among methamphetamine use, increased sex partners and Internet use, the Internet may present a new and effective medium for interventions to reduce methamphetamine-associated sexual risk behavior.

Background: The benefits of antiretroviral therapy during early human immunodeficiency virus type 1 (HIV-1) infection remain unproved., Methods: A5217 study team randomized patients within 6 months of HIV-1 seroconversion to receive either 36 weeks of antiretrovirals (immediate treatment [IT]) or no treatment (deferred treatment [DT]). Patients were to start or restart antiretroviral therapy if they met predefined criteria. The primary end point was a composite of requiring treatment or retreatment and the log(10) HIV-1 RNA level at week 72 (both groups) and 36 (DT group)., Results: At the June 2009 Data Safety Monitoring Board (DSMB) review, 130 of 150 targeted participants had enrolled. Efficacy analysis included 79 individuals randomized ≥72 weeks previously. For the primary end point, the IT group at week 72 had a better outcome than the DT group at week 72 (P = .005) and the DT group at week 36 (P = .002). The differences were primarily due to the higher rate of progression to needing treatment in the DT group (50%) versus the IT (10%) group. The DSMB recommended stopping the study because further follow-up was unlikely to change these findings., Conclusions: Progression to meeting criteria for antiretroviral initiation in the DT group occurred more frequently than anticipated, limiting the ability to evaluate virologic set point. Antiretrovirals during early HIV-1 infection modestly delayed the need for subsequent treatment., Clinical Trials Registration: NCT00090779.

Background: Diffusion, dissemination, and implementation of scientific evidence into routine clinical practice is not well understood. The Adult AIDS Clinical Trials Group (ACTG) Protocol 5164 showed that early antiretroviral therapy (ART; ie, within 14 days) after diagnosis of an opportunistic infection improved clinical outcomes, compared with later initiation. Subsequently, the San Francisco General Hospital (SFGH) HIV/AIDS Service performed the SFGH 5164 Initiative to disseminate and implement the findings of ACTG 5164., Methods: We evaluated patients who received a diagnosis of Pneumocystis jirovecii pneumonia (PCP) from 1 January 2001 through 30 March 2011. Survival analyses were used to assess changes in the time to initiation of ART after PCP, and logistic regression was used to evaluate changes in the odds of early ART (ie, within 14 days) because of ACTG 5164 and SFGH 5164 Initiative., Results: Among 162 patients, the adjusted hazard of ART initiation increased by 3.05 (95% confidence interval [CI], 1.86-5.02) after ACTG 5164 and by 4.89 (95% CI, 2.76-8.67) after the SFGH Initiative, compared with before ACTG 5164. When compared with before ACTG 5164, the proportion of patients who received ART within the 14 days after PCP diagnosis increased from 7.4% to 50.0% (P < .001) after ACTG 5164 and from 50.0% to 83.0% (P = .02) after the SFGH 5164 Initiative., Conclusions: Diffusion of findings from of a randomized trial changed practice at an academic medical center, but dissemination and implementation efforts were required to establish early ART at acceptable levels. Early ART initiation can be achieved in real-world patient populations.

Background: Advances in antiretroviral therapy (ART) over the last decade have improved clinical outcomes for people living with human immunodeficiency virus (HIV), but whether these improvements are experienced by disadvantaged urban populations is less clear., Methods: We evaluated mortality among a clinical cohort in a public safety-net HIV specialty clinic in San Francisco, California., Results: Among 1651 ART-eligible patients attending an urban US HIV clinic, 4-year mortality was 10.0% in 2000-2004 and 11.0% in 2005-2009. Despite universal ART availability, only 72 (42%) of 172 patients who died, compared with 69% of survivors, ever achieved an HIV viral load, 400 copies per cubic millimeter. The leading causes of death were acquired immunodeficiency syndrome (56%), violence/overdose (16%), and pulmonary disease (6%)., Conclusions: Disadvantaged subpopulations in the developed world can experience high mortality rates despite accessing specialty HIV clinical services with full ART availability. New strategies are needed to improve the outcomes in these populations.

Although commercial tests are approved for detection of HIV-1 plasma viral loads ≥ 20 copies per milliliter (ml), only one specialized research assay has been reported to detect plasma viral loads as low as 1 copy/ml. This manuscript describes a method of concentrating HIV-1 virions from up to 30 ml of plasma, which can be combined with a commercial viral load test to create a widely available, reproducible assay for quantifying plasma HIV RNA levels less than 1 copy/ml. Using this pre-analytically modified assay, samples with a known level of 0.5 copy/ml were detected in 8 of 12 replicates (mean 0.47 copy/ml; 95% confidence interval (CI) 0.14-0.81 copy/ml) and samples with a known level of 1.0 copy/ml were detected in 13 of 13 replicates (mean 1.96 copy/ml; 95% CI 1.42-2.50 copy/ml). By concentrating virus from 30 ml of plasma, HIV RNA could be measured in 16 of 19 samples (84%) from 12 of 12 subjects (mean 2.77 copy/ml; 95% CI 0.86-4.68 copy/ml). The measured viral load correlated inversely (r = -0.78; p = 0.028) with the total duration of viral suppression (viral load<40 copies/ml)., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objectives: Although targeted screening of patients at high risk for human immunodeficiency virus (HIV) infection in the emergency department (ED) improves patient outcomes and may prevent HIV transmission, ED-based screening programs incur additional costs and have thus not been widely scaled up. The objective of this study was to evaluate the cost-effectiveness of ED-based targeted HIV screening as implemented in actual practice., Methods: This was a cost-utility analysis of a rapid HIV screening program in an urban ED. Physicians were encouraged to screen patients undergoing inpatient admission or who had HIV risk factors. The authors measured costs directly and estimated quality-adjusted life expectancy using chart review, literature assumptions, and mathematical modeling. Incremental cost utility was evaluated from a societal perspective using a lifetime time horizon., Results: From June 2008 through September 2009, a total of 3,766 HIV tests were ordered (235 tests per month), of which an estimated 2,406 (64%) represented screening in patients without HIV-related signs or symptoms. Nineteen (0.8%) patients were newly diagnosed through screening during the study period, of whom nine (47%) were eligible for antiretroviral therapy (ART) and maintained consistent outpatient follow-up. Estimated screening costs were $82,300 per year, or $45.53 per screening test, of which $28.01 (62%) was for program management. Targeted screening prevented an estimated 2.1 HIV transmission events over 16 months. Per patient screened, targeted screening saved $112 (95% uncertainty range [UR] = $20 to $225) and resulted in 2.71 quality-adjusted life-days gained (95% UR = 1.71 to 4.01). Cost-utility was most sensitive to the prevalence of undiagnosed HIV in the screened population., Conclusions: Targeted HIV screening, as implemented in an urban ED, is cost saving and increases quality-adjusted life expectancy., (© 2011 by the Society for Academic Emergency Medicine.)

The urban emergency department is an important site for the detection of HIV infection. Current research has focused on strategies to increase HIV testing in the emergency department. As more emergency department HIV cases are identified, there need to be well-defined systems for linkage to care. We conducted a retrospective study of rapid HIV testing in an urban public emergency department and level I trauma center from June 1, 2008, to March 31, 2010. The objectives of this study were to evaluate the increase in the number of tests and new HIV diagnoses resulting from the addition of targeted testing to clinician-initiated diagnostic testing, describe the demographic and clinical characteristics of patients with newly diagnosed HIV infection, and assess the effectiveness of an HIV clinic based linkage to care team. Of 96,711 emergency department visits, there were 5340 (5.5%) rapid HIV tests performed, representing 4827 (91.3%) unique testers, of whom 62.4% were male and 60.8% were from racial/ethnic minority groups. After the change in testing strategy, the median number of tests per month increased from 114 to 273 (p=0.004), and the median number of new diagnoses per month increased from 1.5 to 4 (p=0.01). From all tests conducted, there were 65 new diagnoses of HIV infection (1.2%, 95% confidence interval [CI] 0.9%, 1.5%). The linkage team connected over 90% of newly diagnosed and out-of-care HIV-infected patients to care. In summary, the addition of targeted testing to diagnostic testing increased new HIV case identification, and an HIV clinic-based team was effective at linkage to care.

Background: The gut is a major reservoir for human immunodeficiency virus (HIV) in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV., Methods: In 8 HIV-1-positive adults who were receiving ART and had CD4(+) T cell counts of >200 cells/μL and plasma viral loads of <40 copies/mL, levels of HIV and T cell activation were measured in blood samples and endoscopic biopsy specimens from the duodenum, ileum, ascending colon, and rectum., Results: HIV DNA and RNA levels per CD4(+) T cell were higher in all 4 gut sites compared with those in the blood. HIV DNA levels increased from the duodenum to the rectum, whereas the median HIV RNA level peaked in the ileum. HIV DNA levels correlated positively with T cell activation markers in peripheral blood mononuclear cells (PBMCs) but negatively with T cell activation markers in the gut. Multiply spliced RNA was infrequently detected in gut, and ratios of unspliced RNA to DNA were lower in the colon and rectum than in PBMCs, which reflects paradoxically low HIV transcription, given the higher level of T cell activation in the gut., Conclusions: HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA levels and T cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut., Trial Registration: ClinicalTrials.gov identifier: NCT00884793 (PLUS1).

Objective: To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut., Design: Open-label study in HIV-positive adults on ART with plasma HIV RNA below 40 copies/ml., Methods: Seven HIV-positive adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from peripheral blood mononuclear cells (PBMC) and four gut sites, T-cell subsets, and activation markers., Results: Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, five of seven participants had a decrease in unspliced HIV RNA per 10 CD4(+) T cells in the ileum. There was a trend towards decreased T-cell activation in all sites, which was greatest for CD8(+) T cells in the ileum and PBMC, and a trend towards increased CD4(+) T cells in the ileum., Conclusion: Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible.

Acute human immunodeficiency virus type 1 (HIV-1) infection is characterized by high levels of immune activation. Immunomodulation with cyclosporine combined with antiretroviral therapy (ART) in the setting of acute and early HIV-1 infection has been reported to result in enhanced immune reconstitution. Fifty-four individuals with acute and early infection were randomized to receive ART with 4 weeks of cyclosporine versus ART alone. In 48 subjects who completed the study, there were no significant differences between treatment arms in levels of proviral DNA or CD4(+) T cell counts. Adjunctive therapy with cyclosporine in this setting does not provide apparent virologic or immunologic benefit.

This publication contains information from a conference titled "Individual Perspectives on the Silent Epidemic of Viral Hepatitis in Hawai'i" held in October of 2007 with updates and additional contributions from annual conferences in 2008 and 2009. These conferences were sponsored by the Hepatitis Support Network of Hawai'i and held in Honolulu, Hawai'i at the Queen's Conference Center. The primary objectives of the conferences have been to heighten awareness of viral hepatitis in Hawai'i and to bring together health care professionals to learn about these infections and to help them respond to the challenges they bring to the people of Hawai'i. The initial conference was oriented to present the unique and individual perspectives of patients, physicians, and other healthcare providers specific to the complex issues of hepatitis in an effort to help them understand their role in the context of others and to develop a team approach in responding to this epidemic.

Personal health records (PHRs) are information repositories; however, PHRs may be less available to persons in the safety net setting. We deployed a free, secure, internet-based PHR for persons receiving care at the AIDS/HIV clinic at San Francisco General Hospital. In our initial rollout, 221 persons registered for the PHR. Compared to the entire clinic, these initial users were more likely to be Caucasian, male, non-Hispanic, on antiretroviral medications, and have better control of their HIV infection. The median number of online sessions was 7 and the median session length was 4 min. Laboratory results were the most commonly accessed feature. Patients were satisfied with the PHR and more than 80% of users agreed that the PHR helped them manage their medical problems; however, some users were concerned that their health information was not accurate or secure. Patients in a safety net setting will access and use an online PHR.

While numerous studies examine methamphetamine use and associated risky sexual behaviors in HIV-uninfected individuals, few studies have surveyed HIV-infected individuals in the health care setting. To assess the frequency and trends of methamphetamine use, sexual activity, injection drug use, patient-provider communication, and medication adherence among HIV-infected persons in care, we administered a one-page anonymous survey in 2004 and 2006. The survey was conducted at the two University of California, San Francisco outpatient HIV clinics: at Moffitt Hospital (Moffitt), serving primarily privately insured patients, and at San Francisco General Hospital (SFGH), a county hospital serving primarily patients who are uninsured or publicly insured. In 2006, 39% of men who have sex with men (MSM), 33% of heterosexual men, and 11% of women reported methamphetamine use in the prior 12 months. Methamphetamine use was significantly associated with an increased number of sex partners among MSM and heterosexual men, and poor anti-retroviral medication adherence. Among MSM, methamphetamine use was more common at the SFGH clinic. Between 2004 and 2006, reported methamphetamine use in the last 12 months decreased among MSM at Moffitt (38 to 20%, p<0.01), but increased at SFGH (40 to 50%, p<0.05). Among methamphetamine users we found a high frequency of injection of methamphetamine, which increased at SFGH from 38 to 55%, p<0.05. Patient-provider communication regarding methamphetamine use has increased from 2004 to 2006 but no significant change has been found for providers asking patients about sexual activity. Overall, we found methamphetamine use to be common among HIV-infected patients in care, and associated with an increased number of sex partners, a high frequency of injection drug use, and poor adherence to anti-retroviral medications. These findings support the need for improved screening and clinic-based interventions to reduce and treat methamphetamine abuse and associated high risk sexual behaviors.

Background: Linkage to care after HIV diagnosis is associated with both clinical and public health benefits. However, ensuring and monitoring linkage to care by public health departments has proved to be a difficult task. Here, we report the usefulness of routine monitoring of CD4 T cell counts and plasma HIV viral load as measures of entry into care after HIV diagnosis., Methods: Since July 1, 2006, the San Francisco Department of Public Health (SFDPH) incorporated monitoring initial primary care visit into standard HIV public health investigation for newly diagnosed HIV-infected patients in select clinics. Entry into care was defined as having at least one visit to a primary HIV care provider after the initial diagnosis of HIV infection. Investigators collected reports from patients, medical providers, laboratories and reviewed medical records to determine the date of the initial health care visit after HIV diagnosis. We identified factors associated with increased likelihood of entering care after HIV diagnosis., Results: One -hundred and sixty new HIV-infected cases were diagnosed between July 1, 2006 and June 30, 2007. Routine surveillance methods found that 101 of those cases entered HIV medical care and monitoring of CD4 T cell counts and plasma HIV viral load confirmed entry to care of 25 more cases, representing a 25% increase over routine data collection methods. We found that being interviewed by a public health investigator was associated with higher odds of entry into care after HIV diagnosis (OR 18.86 [1.83-194.80], p = .001) compared to cases not interviewed. Also, HIV diagnosis at the San Francisco county hospital versus diagnosis at the county municipal STD clinic was associated with higher odds of entry into care (OR 101.71 [5.29-1952.05], p < .001)., Conclusion: The time from HIV diagnosis to initial CD4 T cell count, CD4 T cell value and HIV viral load testing may be appropriate surveillance measures for evaluating entry into care, as well as performance outcomes for local public health departments' HIV testing programs. Case investigation performed by the public health department or case management by clinic staff was associated with increased and shorter time to entry into HIV medical care.

Using standard and ultrasensitive techniques, we detected nonnucleoside reverse-transcriptase inhibitor-associated resistance mutations in 11 (20%) of 54 subjects who discontinued virologically suppressive nonnucleoside reverse-transcriptase inhibitor-containing antiretroviral therapy. Resistance was detected in 45% and 14% of subjects with a baseline human immunodeficiency virus type 1 RNA level of 51-400 copies/mL and

Background: Populations at highest risk for HIV infection face multiple barriers to HIV testing. To facilitate HIV testing procedures, the San Francisco General Hospital Medical Center eliminated required written patient consent for HIV testing in its medical settings in May 2006. To describe the change in HIV testing rates in different hospital settings and populations after the change in HIV testing policy in the SFDH medical center, we performed an observational study using interrupted time series analysis., Methods: Data from all patients aged 18 years and older seen from January 2003 through June 2007 at the San Francisco Department of Public Health (SFDPH) medical care system were included in the analysis. The monthly HIV testing rate per 1000 had patient-visits was calculated for the overall population and stratified by hospital setting, age, sex, race/ethnicity, homelessness status, insurance status and primary language., Results: By June 2007, the average monthly rate of HIV tests per 1000 patient-visits increased 4.38 (CI, 2.17-6.60, p<0.001) over the number predicted if the policy change had not occurred (representing a 44% increase). The monthly average number of new positive HIV tests increased from 8.9 (CI, 6.3-11.5) to 14.9 (CI, 10.6-19.2, p<0.001), representing a 67% increase. Although increases in HIV testing were seen in all populations, populations at highest risk for HIV infection, particularly men, the homeless, and the uninsured experienced the highest increases in monthly HIV testing rates after the policy change., Conclusions: The elimination of the requirement for written consent in May 2006 was associated with a significant and sustained increase in HIV testing rates and HIV case detection in the SFDPH medical center. Populations facing the higher barriers to HIV testing had the highest increases in HIV testing rates and case detection in response to the policy change.

The US HIV epidemic began in 1981. The number of HIV-infected individuals in the United States and throughout the world is increasing each year. Given the increasing number of HIV-infected individuals, knowledge of the basic pathogenesis of HIV disease and the principles of antiretroviral therapy is important for all healthcare professionals. This article describes epidemiologic trends in HIV and reviews HIV transmission, testing, and treatment. It also discusses the risk of HIV transmission to healthcare workers from occupational exposures and reviews the principles of postexposure prophylaxis used to reduce the likelihood of HIV transmission in appropriate circumstances.

Background: In response to increases in methamphatemine-associated sexually transmitted diseases, the San Francisco Department of Public Health implemented a contingency management (CM) field program called the Positive Reinforcement Opportunity Project (PROP)., Methods: Methamphetamine-using men who have sex with men (MSM) in San Francisco qualified for PROP following expressed interest in the program, provision of an observed urine sample that tested positive for methamphetamine metabolites and self-report of recent methamphetamine use. For 12 weeks, PROP participants provided observed urine samples on Mondays, Wednesdays and Fridays and received vouchers of increasing value for each consecutive sample that tested negative to metabolites of methamphetamine. Vouchers were exchanged for goods and services that promoted a healthy lifestyle. No cash was provided. Primary outcomes included acceptability (number of enrollments/time), impact (clinical response to treatment and cost-effectiveness as cost per patient treated)., Results: Enrollment in PROP was brisk indicating its acceptability. During the first 10 months of operation, 143 men sought treatment and of these 77.6% were HIV-infected. Of those screened, 111 began CM treatment and averaged 15 (42%) methamphetamine-free urine samples out of a possible 36 samples during the 12-week treatment period; 60% completed 4 weeks of treatment; 48% 8 weeks and 30% 12 weeks. Across all participants, an average of $159 (SD = $165) in vouchers or 35.1% of the maximum possible ($453) was provided for these participants. The average cost per participant of the 143 treated was $800., Conclusion: Clinical responses to CM in PROP were similar to CM delivered in drug treatment programs, supporting the adaptability and effectiveness of CM to non-traditional drug treatment settings. Costs were reasonable and less than or comparable to other methamphetamine outpatient treatment programs. Further expansion of programs like PROP could address the increasing need for acceptable, feasible and cost-effective methamphetamine treatment in this group with exceptionally high rates of HIV-infection.

Background: We assessed human immunodeficiency virus (HIV) antibody seroreversion among individuals initiating antiretroviral therapy (ART) during acute/early HIV infection and determined whether seroreversion was associated with loss of cytotoxic T lymphocyte responses., Methods: Subjects in a cohort with acute/early HIV infection (<12 months into infection) who initiated ART within 28 days after study entry and maintained HIV type 1 ribonucleic acid levels of < or =500 copies/mL for >24 weeks were selected. Two clinically available second-generation enzyme immunoassays (EIAs) and a confirmatory Western blot were used to screen subjects for antibody reversion. Those with negative screening test results underwent additional antibody testing, including a third-generation EIA, and were assessed for cytotoxic T lymphocyte responses., Results: Of 87 subjects identified, 12 (14%) had negative antibody test results at the start of ART; all 12 had seroconversion, although 1 had seroconversion only on a third-generation EIA. Of the 87 subjects, 6 (7%) had seroreversion on at least 1 EIA antibody assay while receiving ART during a median follow-up of 90 weeks. The only clinical predictor of seroreversion was a low baseline "detuned" (less sensitive) antibody. Cytotoxic T lymphocyte responses to HIV Gag peptides were detected in 4 of 5 subjects with seroreversion who could be tested. All 5 who had seroreversion who stopped ART experienced virologic rebound and antibody evolution., Conclusions: HIV antibody seroconversion on second-generation EIA antibody tests may fail to occur when ART is initiated early. Seroreversion was not uncommon among subjects treated early, although cytotoxic T lymphocyte responses to HIV antigens remained detectable in most subjects. Antibody seroreversion did not indicate viral eradication. A third-generation EIA was the most sensitive test for HIV antibodies.