Cardiovascular Disease Risk Factor Control in People With and Without HIV.

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.

Prevalence of Undiagnosed Monkeypox Virus Infections during Global Mpox Outbreak, United States, June-September 2022.

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.

Sexually Transmitted Infection Screening in Key Populations of Persons Living with HIV.

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.

Characterizing Unhealthy Alcohol Use Patterns and Their Association with Alcohol Use Reduction and Alcohol Use Disorder During Follow-Up in HIV Care.

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.

Mental health and substance use screening in HIV primary care before and during the early COVID-19 pandemic.

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.

Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial.

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.

HIV Stigma and Its Associations with Longitudinal Health Outcomes Among Persons Living with HIV with a History of Unhealthy Alcohol Use.

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.

RESUMEN: El objetivo de este estudio era examinar la correlación del estigma del VIH con aspectos demográficos y clínicos. Se buscaba evaluar la asociación del estigma del VIH con los efectos de la salud física y mental luego de un año en un cohorte de personas viviendo con VIH (PVV; N = 584) provenientes de una clínica de servicios primarios. El estigma del VIH se midió utilizando la escala modificada de estigma del VIH de Berger que incluye cuatro sub-escalas: (1) estigma personalizado; (2) preocupaciones por revelación de diagnóstico; (3) auto-imagen negativa; y (4) preocupaciones acerca de actitudes hacia PVV. La salud física y mental fue evaluada utilizando una encuesta corta de 12 ítems. En comparación con las personas blancas, entre las personas Afroamericanas había más probabilidad de obtener una mayor puntuación en las escalas de estigma personalizado (razón de prevalencia ajustada [aRP] 1.54 [95% intervalo de confianza 1.10­2.15]), preocupaciones por revelación de diagnóstico (aRP 1.40 [1.03­1.92]), y preocupacionespor actitudes negativas hacia PVV (aRP 1.61 [1.11­2.34]). Participantes Hispanos/Latinos tenían más probabilidad de tener preocupaciones por las actitudes negativas hacia PVV (aRP 1.50 [1.11­2.02]) en comparación con personas blancas. En comparación con los hombres, las mujeres tenían mayor probabilidad de tener un resultado más alto en la escala de auto-imagen negativa (aRP 1.50 [1.08­2.08]). Resultados mayores estuvieron asociados a estatus más pobres de funcionalidad de salud física y mental. Nuestros resultados destacan la necesidad substancial de atender asuntos de estigma por el VIH, particularmente en grupos minoritarios.

Early Adopters of Event-driven Human Immunodeficiency Virus Pre-exposure Prophylaxis in a Large Healthcare System in San Francisco.

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.

Prevalence of Spontaneous Clearance of Hepatitis C Virus Infection Doubled From 1998 to 2017.

Strategic planning for hepatitis C virus (HCV) screening and treatment requires up-to-date information on the prevalence of HCV spontaneous clearance. Published estimates of HCV spontaneous clearance range from 15% to 60%.1-3 We conducted an observational study over 20 years to evaluate trends in the prevalence of HCV spontaneous clearance. Our goals were to estimate the proportion of HCV-antibody-positive patients who were viremic, and to identify factors associated with viremia, thus facilitating prediction of the number of patients needing treatment.

Alcohol and drug use, partner PrEP use and STI prevalence among people with HIV.

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.

Interventions to Reduce Unhealthy Alcohol Use among Primary Care Patients with HIV: the Health and Motivation Randomized Clinical Trial.

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 ).

Successful Implementation of HIV Preexposure Prophylaxis: Lessons Learned From Three Clinical Settings.

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.

No New HIV Infections With Increasing Use of HIV Preexposure Prophylaxis in a Clinical Practice Setting.

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.

Factors associated with suicidal ideation among people with HIV engaged in care.

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.

HIV-1 infection kinetics, drug resistance, and long-term safety of pre-exposure prophylaxis with emtricitabine plus tenofovir alafenamide (DISCOVER): week 144 open-label extension of a randomised, controlled, phase 3 trial.

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 (ß2-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.

The setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1-infected individuals.

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.

Racial, ethnic, and age disparities in the association of mental health symptoms and polysubstance use among persons in HIV care.

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.

The effect of a "universal antiretroviral therapy" recommendation on HIV RNA levels among HIV-infected patients entering care with a CD4 count greater than 500/µL in a public health setting.

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.

Low rates of hepatitis screening and vaccination of HIV-infected MSM in HIV clinics.

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, transmission risk behavior and internet use among HIV-infected patients in medical care, San Francisco, 2008.

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.