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Describe engagement in HIV care over time after initial engagement in HIV care, by gender identity.Observational, clinical cohort study of people with HIV engaged in routine HIV care across the United States.We followed people with HIV who linked to and engaged in clinical care (attending ≥2 visits in 12 months) in cohorts in the North American Transgender Cohort Collaboration, 2000-2018. Within strata of gender identity, we estimated the 7-year (84-month) restricted mean time spent: lost-to-clinic (stratified by pre/postantiretroviral therapy (ART) initiation); in care prior to ART initiation; on ART but not virally suppressed; virally suppressed (≤200 copies/ml); or dead (pre/post-ART initiation).Transgender women ( N = 482/101 841) spent an average of 35.5 out of 84 months virally suppressed (this was 30.5 months for cisgender women and 34.4 months for cisgender men). After adjustment for age, race, ethnicity, history of injection drug use, cohort, and calendar year, transgender women were significantly less likely to die than cisgender people. Cisgender women spent more time in care not yet on ART, and less time on ART and virally suppressed, but were less likely to die compared with cisgender men. Other differences were not clinically meaningful.In this sample, transgender women and cisgender people spent similar amounts of time in care and virally suppressed. Additional efforts to improve retention in care and viral suppression are needed for all people with HIV, regardless of gender identity.

Overdoses continue to increase in the US, but the contribution of methamphetamine use is understudied in rural communities.To estimate the prevalence of methamphetamine use and its correlates among people who use drugs (PWUD) in rural US communities and to determine whether methamphetamine use is associated with increased nonfatal overdoses.From January 2018 through March 2020, the National Rural Opioid Initiative conducted cross-sectional surveys of PWUD in rural communities in 10 states (Illinois, Kentucky, New Hampshire, Massachusetts, North Carolina, Ohio, Oregon, Vermont, West Virginia, and Wisconsin). Participants included rural PWUD who reported any past-30-day injection drug use or noninjection opioid use to get high. A modified chain-referral sampling strategy identified seeds who referred others using drugs. Data analysis was performed from May 2021 to January 2022.Use of methamphetamine alone, opioids alone, or both.Unweighted and weighted prevalence of methamphetamine use, any past-180-day nonfatal overdose, and number of lifetime nonfatal overdoses.Among the 3048 participants, 1737 (57%) were male, 2576 (85%) were White, and 225 (7.4%) were American Indian; the mean (SD) age was 36 (10) years. Most participants (1878 of 2970 participants with any opioid or methamphetamine use [63%]) reported co-use of methamphetamine and opioids, followed by opioids alone (702 participants [24%]), and methamphetamine alone (390 participants [13%]). The estimated unweighted prevalence of methamphetamine use was 80% (95% CI, 64%-90%), and the estimated weighted prevalence was 79% (95% CI, 57%-91%). Nonfatal overdose was greatest in people using both methamphetamine and opioids (395 of 2854 participants with nonmissing overdose data [22%]) vs opioids alone (99 participants [14%]) or methamphetamine alone (23 participants [6%]). Co-use of methamphetamine and opioids was associated with greater nonfatal overdose compared with opioid use alone (adjusted odds ratio, 1.45; 95% CI, 1.08-1.94; P = .01) and methamphetamine use alone (adjusted odds ratio, 3.26; 95% CI, 2.06-5.14; P .001). Those with co-use had a mean (SD) of 2.4 (4.2) (median [IQR], 1 [0-3]) lifetime overdoses compared with 1.7 (3.5) (median [IQR], 0 [0-2]) among those using opioids alone (adjusted rate ratio, 1.20; 95% CI, 1.01-1.43; P = .04), and 1.1 (2.9) (median [IQR], 0 [0-1]) among those using methamphetamine alone (adjusted rate ratio, 1.81; 95% CI, 1.45-2.27; P .001). Participants with co-use most often reported having tried and failed to access substance use treatment: 827 participants (44%) for both, 117 participants (30%) for methamphetamine alone, and 252 participants (36%) for opioids alone (χ22 = 33.8; P .001). Only 66 participants (17%) using methamphetamine alone had naloxone.These findings suggest that harm reduction and substance use disorder treatment interventions must address both methamphetamine and opioids to decrease overdose in rural communities.

Direct-acting antivirals (DAA) are highly effective against hepatitis C virus (HCV) infection among persons with human immunodeficiency virus (PWH). However, alcohol use post-DAA treatment poses a continued threat to the liver. Whether the focus on liver health alone during HCV treatment can impact alcohol consumption is unclear. Therefore, we examined the change in alcohol use among HCV-coinfected PWH who received DAA therapy by non-addiction medical providers.In our longitudinal clinical cohort study, we identified HCV-coinfected PWH who received interferon-free DAA therapy between January 2014 and June 2019 in the Centers for AIDS Research Network of Integrated Clinical Systems. The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) was the alcohol screening instrument. We used mixed-effects logistic regression models to estimate the longitudinal change in alcohol use upon DAA therapy.Among 738 HCV-coinfected PWH, 339 (46 %) reported any alcohol use at the end of HCV treatment, including 113 (15 %) with high-risk use (i.e., AUDIT-C ≥3 for women, ≥4 for men). Concurrently, 280 (38 %) PWH noted active drug use, and 357 (48 %) were currently smoking. We observed no changes in the odds of any alcohol or high-risk alcohol use over time with DAA therapy. Findings were similar in the PWH subgroup with a history of alcohol use before DAA treatment.For PWH with HCV, alcohol use did not change following interferon-free DAA treatment by non-addiction medical providers. Thus, clinicians should consider integrating targeted alcohol use interventions into HCV care to motivate reduced alcohol consumption and safeguard future liver health.

In an analysis of randomized trials, use of efavirenz for treatment of human immunodeficiency virus (HIV) infection was associated with increased suicidal thoughts/behaviors. However, analyses of observational data have found no evidence of increased risk. To assess whether population differences might explain this divergence, we transported the effect of efavirenz use from these trials to a specific target population. Using inverse odds weights and multiple imputation, we transported the effect of efavirenz on suicidal thoughts/behaviors in these randomized trials (participants were enrolled in 2001–2007) to a trials-eligible cohort of US adults initiating antiretroviral therapy while receiving HIV clinical care at medical centers between 1999 and 2015. Overall, 8,291 cohort participants and 3,949 trial participants were eligible. Prescription of antidepressants (19% vs. 13%) and injection drug history (16% vs. 10%) were more frequent in the cohort than in the trial participants. Compared with the effect in trials, the estimated hazard ratio for efavirenz on suicidal thoughts/behaviors was attenuated in our target population (trials: hazard ratio (HR) = 2.3 (95% confidence interval (CI): 1.2, 4.4); transported: HR = 1.8 (95% CI: 0.9, 4.4)), whereas the incidence rate difference was similar (trials: HR = 5.1 (95% CI: 1.6, 8.7); transported: HR = 5.4 (95% CI: −0.4, 11.4)). In our target population, there was greater than 20% attenuation of the hazard ratio estimate as compared with the trials-only estimate. Transporting results from trials to a target population is informative for addressing external validity.

Rates of chronic pain and cigarette smoking are each substantially higher among people living with HIV (PLWH) than in the general population. The goal of these analyses was to examine the prevalence and impact of comorbid chronic pain and cigarette smoking among PLWH. Participants included 3289 PLWH (83% male) who were recruited from five HIV clinics. As expected, the prevalence of smoking was higher among PLWH with chronic pain (41.9%), than PLWH without chronic pain (26.6%, p < .0001), and the prevalence of chronic pain was higher among current smokers (32.9%), than among former (23.6%) or never (17%) smokers (ps < .0001). PLWH who endorsed comorbid chronic pain and smoking (vs. nonsmokers without chronic pain) were more likely to report cocaine/crack and cannabis use, be prescribed long-term opioid therapy, and have virologic failure, even after controlling for relevant sociodemographic and substance-related variables (ps < .05). These results contribute to a growing empirical literature indicating that chronic pain and cigarette smoking frequently co-occur, and extend this work to a large sample of PLWH. Indeed, PLWH may benefit from interventions that are tailored to address bidirectional pain-smoking effects in the context of HIV.

Background Type 1 myocardial infarctions (T1MIs) result from atherosclerotic plaque instability, rupture, and/or erosion. Type 2 MIs (T2MIs) are secondary to causes such as sepsis and cocaine-induced vasospasm resulting in an oxygen demand-supply mismatch and are associated with higher mortality than T1MIs. T2MIs account for a higher proportion of MIs among people living with HIV (PLWH) compared with the general population. We compared MI rates by type among aging PLWH. We hypothesized that increases in MI rates with older age would differ by MI types, and T2MIs would be more common than T1MIs in younger individuals. Methods Potential MIs from 6 sites were centrally adjudicated using physician notes, electrocardiograms, procedure results, and laboratory results. Reviewers categorized MIs by type and identified causes of T2MIs. We calculated T1MI and T2MI incidence rates. Incidence rate ratios were calculated for T2MI vs. T1MI rates per decade of age. Results We included 462 T1MIs (52%) and 413 T2MIs (48%). T1MI rates increased with older age, although T1MIs occurred in all age decades including young adults. T2MI rates were significantly higher than T1MI rates for PLWH younger than 40 years. T1MI rates were similar or higher than T2MI rates among those older than 40 years (significantly higher for those aged 50-59 and 60-69 years). Conclusions Rates of T2MIs were higher than T1MIs until age 40 years among PLWH, differing from the general population, but rates of both were high among older PLWH. Given prognostic differences between MI types, these results highlight the importance of differentiating MI types among PLWH.

End-stage liver disease (ESLD) is a leading cause of non-AIDS-related death among people with HIV (PWH). Factors that increase the progression of liver disease include comorbidities and HIV-specific factors, but we currently lack a tool to apply this evidence into clinical practice.We developed and validated a risk prediction model for ESLD among PWH who received care in 12 cohorts of the North American AIDS Cohort Collaboration on Research and Design between 2000 and 2016 and had fibrosis-4 index1.45. The first occurrence of ascites, variceal bleed, spontaneous bacterial peritonitis, or hepatic encephalopathy was verified by standardized medical record review. The Bayesian model averaging was used to select predictors among biomarkers and diagnoses and the Harrell C statistic to assess model discrimination.Among 13,787 PWH in the training set, 82% were men and 54% were Black with a mean age of 48 years. Three hundred ninety ESLD events occurred over a mean 5.4 years. Among the ESLD cases, 52% had hepatitis C virus, 15% hepatitis B virus, and 31% alcohol use disorder. Twelve factors together predicted ESLD risk moderately well (C statistic 0.79, 95% confidence interval: 0.76 to 0.81): age, sex, race/ethnicity, chronic hepatitis B or C, and routinely collected laboratory values reflecting hepatic impairment (serum albumin, aspartate aminotransferase, total bilirubin, and platelets) and lipid metabolism (triglycerides, high-density lipoprotein, and total cholesterol). Our model performed well in the test set (C statistic 0.81, 95% confidence interval: 0.76 to 0.86).This model of readily accessible clinical parameters predicted ESLD in a large diverse population of PWH.

We assessed acceptability/usability of tablet-based patient-reported outcome (PRO) assessments among patients in HIV care, and relationships with health outcomes using a modified version of the 6-item Acceptability E-Scale (AES) within a self-administered PRO assessment. Using multivariable linear regression, we measured associations between patient characteristics and continuous combined AES score. Among 786 patients (median age=48; 91% male; 49% white; 17% Spanish-speaking) overall mean score was 26/30 points (SD: 4.4). Mean scores per dimension (max 5, 1=lowest acceptability, 5=highest): ease of use 4.7, understandability 4.7, time burden 4.3, overall satisfaction 4.3, helpfulness describing symptoms/behaviors 4.2, and enjoyability 3.8. Higher overall score was associated with race/ethnicity (+1.3 points/African-American patients (95%CI:0.3-2.3); +1.6 points/Latino patients (95%CI:0.9-2.3) compared to white patients). Patients completing PROs in Spanish scored +2.4 points on average (95%CI:1.6-3.3). Higher acceptability was associated with better quality of life (0.3 points (95%CI:0.2-0.5)) and adherence (0.4 points (95%CI:0.2-0.6)). Lower acceptability was associated with: higher depression symptoms (−0.9 points (95%CI:-1.4 to −0.4)); recent illicit opioid use (−2.0 points (95%CI:-3.9 to −0.2)); multiple recent sex partners (−0.8 points (95%CI:−1.5 to −0.1)). While patients endorsing depression symptoms, recent opioid use, condomless sex, or multiple sex partners found PROs to be less acceptable, overall, patients found self-administered, tablet-based PRO assessments to be highly acceptable and easy to use.

Objective: The objective of the study was to evaluate a novel measure of HIV care engagement in a large sample of non-Latino White, Latino, and African American patients. The Index of Engagement in HIV care (the Index) measures the degree to which a patient feels engaged/disengaged from HIV care. However, its measurement invariance, or the degree to which observed scores can be meaningfully compared across racial/ethnic groups, has not been established. Methods: The 10-item Index is a self-report measure initially validated in the Center for AIDS Research Network of Integrated Systems cohort study. Using Center for AIDS Research Network of Integrated Systems survey data, Index scores were linked to patients' electronic medical records, which included viral load (VL) and appointment attendance data. We conducted measurement invariance analyses to test the Index's performance in the 3 racial/ethnic groups and its cross-sectional association with VL and retention in HIV care (2 primary outcomes). Results: A total of 3,127 patients completed the Index, which showed good reliability across the 3 groups (alphas >.84). Confirmatory factor analysis model fit statistics showed that the Index demonstrated configural, metric, and scalar invariance, supporting the conclusion that the Index is a single factor construct. Lastly, lower Index scores associated with a concurrent detectable VL and poor retention in HIV care for all 3 groups. Conclusion: Having demonstrated invariance, the Index scores can be used to compare engagement levels across non-Latino Whites, Latinos, and African Americans in HIV care settings. Improving HIV care retention requires tools that can accurately identify people struggling to stay engaged in HIV care, especially racial/ethnic minorities. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: An optimal adherence to antiretroviral therapy (ART) is fundamental for suppression of HIV viral load and favourable treatment outcomes. Patient-reported outcomes (PROs) are effective tools for improving patient–provider communication and focusing providers’ awareness on current health problems. The objectives of this analysis were (1) to determine the feasibility of implementing an electronic screening tool to measure PROs in a Canadian HIV clinic to obtain information on ART adherence and related factors and (2) to determine the factors related to sub-optimal adherence. Methods: This implementation research with a convenience sample of 600 people living with HIV (PLWH) was conducted in a busy, academic, urban HIV clinic in Toronto, Canada. PLWH were approached to participate in PRO assessments just prior to their in-clinic appointments, including health-related domains such as mental health, housing, nutrition, financial stress and medication adherence, and responses were summarized on a single sheet available for providers to review. Feasibility of implementing PROs was assessed by quantifying response rate, completion rate, time taken and participation rate. Medication adherence was elicited by self-report of the percentage of prescribed HIV medications taken in the last month. Unadjusted and adjusted odds ratios were estimated from logistic regression models to identify factors associated with adherence of

Evidence suggests priorities differ between patients in HIV care and their providers regarding topics most important to address in care. At five U.S. sites, we asked patients and providers to prioritize 25 potential topic areas to address during routine visits, and invited patients to discuss selection rationale. Patients (n = 206) and providers (n = 17) showed high discordance in rank order priorities (X2 (24, 223) = 71.12; p

Background Self-reported antiretroviral therapy (ART) adherence measures that are associated with plasma viral load (VL) are valuable to clinicians and researchers, but are rarely examined among groups vulnerable to dropping out of care. One-seventh of all those living with HIV pass through incarceration annually and criminal-justice (CJ) involved people living with HIV (PLH) are vulnerable to falling out of care. We examined the association of self-reported ART adherence with VL in a criminal-justice sample compared to a routine-care sample. Methods Samples: We examined data from a multisite collaboration of studies addressing the continuum of HIV care among CjJ involved persons in the Seek, Test, Treat, and Retain cohort. Data pooled from seven CJ- studies (n = 414) were examined and compared with the routine-care sample from the Centers for AIDS Research Network of Integrated Clinical Systems’ seven sites (n = 11,698). Measures: In both samples, data on self-reported percent ART doses taken were collected via the visual analogue scale adherence measure. Viral load data were obtained by blood-draw. Analysis: We examined the associations of adherence with VL in both cohorts using mixed effects linear regression of log-VL, and mixed effects logistic regression of binary VL (≥ 200 copies/mL) outcomes. Interactions by CD4 count and self-reported health status were also tested. Results Among the CJ sample, the coefficient for log-VL was − 0.31 (95% CI = − 0.43, − 0.18; P P P P Conclusions The visual analogue scale is valid and useful to measure ART adherence, supporting treatment for CJ- involved PLH vulnerable to falling out of care. Research should examine adherence and VL in additional populations.

Background The relationship of internalized HIV stigma to key care cascade metrics in the United States is not well established using large-scale, geographically diverse data. Setting Center for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort study. Methods Beginning in February 2016, we administered a yearly, validated 4-item internalized HIV stigma scale (response scale 1 = strongly disagree to 5 = strongly agree, Cronbach's alpha 0.91) at 7 CNICS sites and obtained cohort data through November 2017. We compared mean stigma levels by sociodemographic characteristics and used multivariable logistic regression, controlling for the same sociodemographic covariates, to evaluate the association between mean stigma and (1) concurrent viremia; (2) missed visits; and (3) poor visit constancy. We used inverse probability weighting (IPW) to account for differences between patients who did and did not undergo stigma assessment. Results Of 13,183 CNICS patients, 6448 (49%) underwent stigma assessment. Mean stigma was 1.99 (SD 1.07), and 28.6% agreed/strongly agreed with at least 1 stigma question. Patients younger than 50 years, racial/ethnic minorities, cis-women, and heterosexuals had higher mean stigma. Mean stigma score was associated with concurrent viremia [adjusted odds ratio (AOR) 1.13, 95% confidence interval (CI): 1.02 to 1.25, P 0.02], missed visits (AOR 1.10, 95% CI: 1.02 to 1.19, P 0.01), and poor visit constancy, although the effect on visit constancy was attenuated in the IPW model (AOR 1.05, 95% CI: 0.98 to 1.13, P 0.17). Conclusions Higher internalized HIV stigma had a modest but statistically significant association with concurrent viremia and poor retention in care. Further inquiry with prospective analyses is warranted.

Low perceived social support negatively impacts health outcomes. HIV-related stigma may hinder social support. We developed a measure of perceived social support for use in HIV care. We developed a pool of legacy social support items based on literature review. We categorized items similar in content and winnowed items within each of these categories to the strongest alternatives using a qualitative item review process. We designed an interview guide representative of content areas, conducted concept elicitation interviews with patients in English/Spanish, and coded transcripts to match item pool content. We developed new items for salient unrepresented content. In focus groups, patients prioritized highly matched items. We performed cognitive interviews with patients on resulting high-priority items. We performed validity testing on final items against two legacy social support measures. From concept elicitation interviews (n=32), we matched the following concepts: sense of belonging/inclusion (e.g., feeling part of a community/group); communication (e.g., sharing thoughts/feelings with others, and vice-versa); emotional support (feeling loved/liked/cared about); feeling accepted by others as a person; companionship (e.g., fun with others); practical support (e.g., feeling that others in your life would offer tangible support). We identified a new concept: feeling supported by friends/family in remaining healthy. Focus groups (n=23) prioritized highly emotional support, communication, and support to remain healthy. Cognitive interviews (n=30) found most items were well-understood; we revised or omitted those that were not. The final 8-item measure performed well when administered to patients (n=708), with good construct validity. We used an Item Response Theory program to create a 3-item Short Form version of the measure, which captures 96% of patients indicating low social support. We developed the Multifactoral Assessment of Perceived Social Support (MAPSS) and Short Form (MAPSS-SF), which are brief, clinically relevant, sufficiently unidimensional measures of social support for use with patients living with HIV.

BACKGROUND: People living with HIV (PLWH) commonly report marijuana use for chronic pain, though there is limited empirical evidence to support its use. There is hope that marijuana may reduce prescription opioid use. Our objective was to investigate whether marijuana use among PLWH who have chronic pain is associated with changes in pain severity and prescribed opioid use (prescribed opioid initiation and discontinuation). METHODS: Participants completed self-report measures of chronic pain and marijuana use at an index visit and were followed for one year in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). Self-reported marijuana use was the exposure variable. Outcome variables were changes in pain and initiation or discontinuation of opioids during the study period. The relationship between exposure and outcomes was assessed using generalized linear models for pain and multivariable binary logistic regression models for opioid initiation/discontinuation. RESULTS: Of 433 PLWH and chronic pain, 28% reported marijuana use in the past 3 months. Median pain severity at the index visit was 6.3/10 (IQR 4.7–8.0). Neither increases nor decreases in marijuana use were associated with changes in pain severity and marijuana use was not associated with either lower odds of opioid initiation or higher odds of opioid discontinuation. CONCLUSIONS: We did not find evidence that marijuana use in PLWH is associated with improved pain outcomes, or reduced opioid prescribing. This suggests that caution is warranted when counseling PLWH about potential benefits of recreational or medical marijuana.

BackgroundEngagement in care is critical to achieving and sustaining optimal benefits of efficacious antiretroviral therapies for HIV infection. Current metrics of engagement in care, including problematic patterns of retention in care, adherence to treatment, and viral suppression, are often detected late in the disengagement process. We sought to develop and validate a patient-centered screener of engagement in care that can be used to identify deficits in patient perceptions of engagement before the development of poor outcomes, including loss to follow-up, treatment nonadherence, virologic failure, and the resulting increased likelihood of HIV-associated morbidity and mortality and onward transmission of HIV.Setting and methodsUsing input from patients, providers, and researchers through in-person focus groups and an online Delphi process, we developed a self-report measure of engagement in care that was validated with 3296 patients from 7 clinics across the United States.ResultsResults supported a single dimension of engagement in care measured by 10 items. Lower scores on the HIV Index were related to higher depression and anxiety symptoms, greater use of alcohol and stimulants, and increased likelihood of reporting internalized HIV stigma. Higher Index scores were positively associated with self-report measures of antiretroviral therapy adherence, corroborative clinic records documenting appointment attendance, and increased likelihood of recent viral load suppression.ConclusionsThe HIV Index offers promise as a patient-centered diagnostic and prognostic screener for engagement in care that can be used to trigger interventions to promote better clinical outcomes for persons living with HIV.

Background The updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)–specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality. Methods Because complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age 500 copies/mL, CD4 count Results Among 37230 PWH in VACS and 8061 PWH in the NA-ACCORD subset, median age was 53 and 44 years; 3% and 19% were women; and 48% and 39% were black. Discrimination in NA-ACCORD (C-statistic = 0.842 [95% confidence interval {CI}, .830–.854]) was better than in VACS (C-statistic = 0.813 [95% CI, .809–.817]). Predicted and observed mortality largely overlapped in VACS and the NA-ACCORD subset, overall and within subgroups. Conclusions Based on this validation, VACS Index 2.0 can reliably estimate probability of all-cause mortality, at various follow-up times, among PWH in North America.

Advances in antiretroviral therapies have greatly improved the survival of people living with human immunodeficiency virus (HIV) infection (PLWH); yet, PLWH have a higher risk of cardiovascular disease than those without HIV. While numerous genetic loci have been linked to cardiometabolic risk in the general population, genetic predictors of the excessive risk in PLWH are largely unknown.We screened for common and HIV-specific genetic variants associated with variation in lipid levels in 6284 PLWH (3095 European Americans [EA] and 3189 African Americans [AA]), from the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Genetic hits found exclusively in the PLWH cohort were tested for association with other traits. We then assessed the predictive value of a series of polygenic risk scores (PRS) recapitulating the genetic burden for lipid levels, type 2 diabetes (T2D), and myocardial infarction (MI) in EA and AA PLWH.We confirmed the impact of previously reported lipid-related susceptibility loci in PLWH. Furthermore, we identified PLWH-specific variants in genes involved in immune cell regulation and previously linked to HIV control, body composition, smoking, and alcohol consumption. Moreover, PLWH at the top of European-based PRS for T2D distribution demonstrated a 2-fold increased risk of T2D compared to the remaining 95% in EA PLWH but to a much lesser degree in AA. Importantly, while PRS for MI was not predictive of MI risk in AA PLWH, multiethnic PRS significantly improved risk stratification for T2D and MI.Our findings suggest that genetic loci involved in the regulation of the immune system and predisposition to risky behaviors contribute to dyslipidemia in the presence of HIV infection. Moreover, we demonstrate the utility of the European-based and multiethnic PRS for stratification of PLWH at a high risk of cardiometabolic diseases who may benefit from preventive therapies.

Author(s): Satyanarayana, Satyanand; Safren, Steven A; Rogers, Brooke G; Bainter, Sierra A; Christopoulos, Katerina A; Fredericksen, Rob J; Mathews, William C; Moore, Richard D; Mugavero, Michael J; Napravnik, Sonia; Carrico, Adam W; Mimiaga, Matthew J; Mayer, Kenneth H; Crane, Heidi M | Abstract: IntroductionLittle is known about onward HIV transmissions from people living with HIV (PLWH) in care. Antiretroviral therapy (ART) has increased in potency, and treatment as prevention (TasP) is an important component of ending the epidemic. Syndemic theory has informed modelling of HIV risk but has yet to inform modelling of HIV transmissions.MethodsData were from 61,198 primary HIV care visits for 14,261 PLWH receiving care through the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) at seven United States (U.S.) sites from 2007 to 2017. Patient-reported outcomes and measures (PROs) of syndemic conditions - depressive symptoms, anxiety symptoms, drug use (opiates, amphetamines, crack/cocaine) and alcohol use - were collected approximately four to six months apart along with sexual behaviours (meann=n4.3 observations). Counts of syndemic conditions, HIV sexual risk group and time in care were modelled to predict estimated HIV transmissions resulting from sexual behaviour and viral suppression status (HIV RNAnln400/mL) using hierarchical linear modelling.ResultsPatients averaged 0.38 estimated HIV transmissions/100 patients/year for all visits with syndemic conditions measured (down from 0.83, first visit). The final multivariate model showed that per 100 patients, each care visit predicted 0.05 fewer estimated transmissions annually (95% confidence interval (CI): 0.03 to 0.06; pnln0.0005). Cisgender women, cisgender heterosexual men and cisgender men of undisclosed sexual orientation had, respectively, 0.47 (95% CI: 0.35 to 0.59; pnln0.0005), 0.34 (95% CI: 0.20 to 0.49; pnln0.0005) and 0.22 (95% CI: 0.09 to 0.35; pnln0.005) fewer estimated HIV transmissions/100 patients/year than cisgender men who have sex with men (MSM). Each within-patient syndemic condition predicted 0.18 estimated transmissions/100 patients/year (95% CI: 0.12 to 0.24; pnln0.0005). Each between-syndemic condition predicted 0.23 estimated HIV transmissions/100 patients/year (95% CI: 0.17 to 0.28; pnln0.0005).ConclusionsEstimated HIV transmissions among PLWH receiving care in well-resourced U.S. clinical settings varied by HIV sexual risk group and decreased with time in care, highlighting the importance of TasP efforts. Syndemic conditions remained a significant predictor of estimated HIV transmissions notwithstanding the effects of HIV sexual risk group and time in care.

Author(s): Wagman, Jennifer A; Wynn, Adriane; Matsuzaki, Mika; Gnatienko, Natalia; Metsch, Lisa R; Del Rio, Carlos; Feaster, Daniel J; Nance, Robin M; Whitney, Bridget M; Delaney, Joseph AC; Kahana, Shoshana Y; Crane, Heidi M; Chandler, Redonna K; Elliott, Jennifer C; Altice, Frederick; Lucas, Gregory M; Mehta, Shruti H; Hirsch-Moverman, Yael; El-Sadr, Wafaa M; Vu, Quan; Nguyen Thanh, Binh; Springer, Sandra A; Tsui, Judith I; Samet, Jeffrey H | Abstract: ObjectivesIn high-income countries, hazardous alcohol use is associated with reduced receipt of antiretroviral therapy (ART) and viral suppression among people living with HIV (PLHIV) who inject drugs. These associations are less understood in lower middle-income countries (LMIC) and upper middle-income countries.DesignWe examined associations between hazardous alcohol use, ART receipt, and viral suppression among PLHIV who reported current or former injection drug use. Participants were from nine studies in the United States (high-income country), India (LMIC), Russia (upper middle-income country), and Vietnam (LMIC).MethodsHazardous alcohol use was measured via Alcohol Use Disorders Identification Test. Outcomes were HIV viral suppression (viral load of l1000 RNA copies/ml) and self-reported ART receipt. Logistic regression assessed associations between hazardous alcohol use and both outcome variables, controlling for age and sex, among participants with current and former injection drug use.ResultsAmong 2790 participants, 16% were women, mean age was 37.1 ± 9.5 years. Mean Alcohol Use Disorders Identification Test scores were 4.6 ± 8.1 (women) and 6.2 ± 8.3 (men); 42% reported ART receipt; 40% had viral suppression. Hazardous alcohol use was significantly associated with reduced ART receipt in India (adjusted odds ratio = 0.59, 95% confidence interval: 0.45-0.77, P l 0.001); and lower rates of viral suppression in Vietnam (adjusted odds ratio = 0.51, 95% confidence interval: 0.31-0.82, P = 0.006).ConclusionAssociations between hazardous alcohol use, ART receipt, and viral suppression varied across settings and were strongest in LMICs. Addressing hazardous alcohol use holds promise for improving HIV continuum of care outcomes among PLHIV who inject drugs. Specific impact and intervention needs may differ by setting.

Background Advances in antiretroviral therapies have greatly improved the survival of people living with human immunodeficiency virus (HIV) infection (PLWH); yet, PLWH have a higher risk of cardiovascular disease than those without HIV. While numerous genetic loci have been linked to cardiometabolic risk in the general population, genetic predictors of the excessive risk in PLWH are largely unknown. Methods We screened for common and HIV-specific genetic variants associated with variation in lipid levels in 6284 PLWH (3095 European Americans [EA] and 3189 African Americans [AA]), from the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Genetic hits found exclusively in the PLWH cohort were tested for association with other traits. We then assessed the predictive value of a series of polygenic risk scores (PRS) recapitulating the genetic burden for lipid levels, type 2 diabetes (T2D), and myocardial infarction (MI) in EA and AA PLWH. Results We confirmed the impact of previously reported lipid-related susceptibility loci in PLWH. Furthermore, we identified PLWH-specific variants in genes involved in immune cell regulation and previously linked to HIV control, body composition, smoking, and alcohol consumption. Moreover, PLWH at the top of European-based PRS for T2D distribution demonstrated a > 2-fold increased risk of T2D compared to the remaining 95% in EA PLWH but to a much lesser degree in AA. Importantly, while PRS for MI was not predictive of MI risk in AA PLWH, multiethnic PRS significantly improved risk stratification for T2D and MI. Conclusions Our findings suggest that genetic loci involved in the regulation of the immune system and predisposition to risky behaviors contribute to dyslipidemia in the presence of HIV infection. Moreover, we demonstrate the utility of the European-based and multiethnic PRS for stratification of PLWH at a high risk of cardiometabolic diseases who may benefit from preventive therapies.

Background Most studies of stroke in people living with HIV (PLWH) do not use verified stroke diagnoses, are small, and/or do not differentiate stroke types and subtypes. Setting CNICS, a U.S. multisite clinical cohort of PLWH in care. Methods We implemented a centralized adjudication stroke protocol to identify stroke type, subtype, and precipitating conditions identified as direct causes including infection and illicit drug use in a large diverse HIV cohort. Results Among 26,514 PLWH, there were 401 strokes, 75% of which were ischemic. Precipitating factors such as sepsis or same-day cocaine use were identified in 40% of ischemic strokes. Those with precipitating factors were younger, had more severe HIV disease, and fewer traditional stroke risk factors such as diabetes and hypertension. Ischemic stroke subtypes included cardioembolic (20%), large vessel atherosclerosis (13%), and small vessel (24%) ischemic strokes. Individuals with small vessel strokes were older, were more likely to have a higher current CD4 cell count than those with cardioembolic strokes and had the highest mean blood pressure of the ischemic stroke subtypes. Conclusion Ischemic stroke, particularly small vessel and cardioembolic subtypes, were the most common strokes among PLWH. Traditional and HIV-related risk factors differed by stroke type/subtype. Precipitating factors including infections and drug use were common. These results suggest that there may be different biological phenomena occurring among PLWH and that understanding HIV-related and traditional risk factors and in particular precipitating factors for each type/subtype may be key to understanding, and therefore preventing, strokes among PLWH.

To further explore genetic links between complex traits, we developed a comprehensive framework to harmonize and integrate extensive genotype and phenotype data from the four well-characterized cohorts with the focus on cardiometabolic diseases deposited to the database of Genotypes and Phenotypes (dbGaP). We generated a series of polygenic risk scores (PRS) to investigate pleiotropic effects of loci that confer genetic risk for 19 common diseases and traits on body height, type 2 diabetes (T2D), and myocardial infarction (MI). In a meta-analysis of 20,021 subjects, we identified shared genetic determinants of Crohn’s Disease (CD), a type of inflammatory bowel disease, and body height (p = 5.5 × 10–5). The association of PRS-CD with height was replicated in UK Biobank (p = 1.1 × 10–5) and an independent cohort of 510 CD cases and controls (1.57 cm shorter height per PRS-CD interquartile increase, p = 5.0 × 10−3 and a 28% reduction in CD risk per interquartile increase in PRS-height, p = 1.1 × 10–3, with the effect independent of CD diagnosis). A pathway analysis of the variants overlapping between PRS-height and PRS-CD detected significant enrichment of genes from the inflammatory, immune-mediated and growth factor regulation pathways. This finding supports the clinical observation of growth failure in patients with childhood-onset CD and demonstrates the value of using individual-level data from dbGaP in searching for shared genetic determinants. This information can help provide a refined insight into disease pathogenesis and may have major implications for novel therapies and drug repurposing.

Objective We sought to examine the prospective association between internalized HIV stigma and unsuppressed viral load and to investigate whether this relationship was sequentially mediated by depressive symptoms and antiretroviral therapy (ART) adherence. Design Longitudinal study in a multisite observational clinical cohort. Methods The Center for AIDS Research Network of Integrated Clinical Systems patient-reported outcomes survey measures internalized HIV stigma yearly using a four-item assessment (response scale 1 = strongly disagree to 5 = strongly agree). We obtained patient-reported outcome, lab, and appointment data from six center for AIDS research network of integrated clinical systems sites. We used multivariable logistic regression to examine the association between mean stigma and subsequent viremia. We then used Bayesian sequential mediation to fit a longitudinal sequential path model spanning four time points to test if depressive symptoms at T1 and ART adherence at T2 mediated the effect of stigma at T0 on viral load at T3, adjusting for baseline covariates. Results Between February 2016 and November 2018, 6859 patients underwent stigma assessment and were 81% cis-men, 38% Black, 16% Latinx, 32% heterosexual-identified, and 49% at least 50 years of age. Mean stigma level was 2.00 (SD 1.08). Stigma was significantly associated with subsequent viremia (adjusted odds ratio = 1.16, 95% confidence interval: 1.05-1.28, P = 0.004), as were younger age and Black race. The chained indirect effect from stigma to unsuppressed viral load through depressive symptoms and then adherence was significant (standardized β = 0.002; SD = 0.001). Conclusion Internalized HIV stigma positively predicts subsequent viremia through depressive symptoms and ART adherence. Addressing the link between stigma and depressive symptoms could help improve viral suppression.

Background We analyzed the association between substance use (SU) and condomless sex (CS) among HIV-negative adults reporting heterosexual sex in the Seek, Test, Treat, and Retain (STTR) consortium. We describe the impact of SU as well as person/partner and context-related factors on CS, identifying combinations of factors that indicate the highest likelihood of CS. Methods We analyzed data from four US-based STTR studies to examine the effect of SU on CS using two SU exposures: 1) recent SU (within 3 months) and 2) SU before/during sex. Behavioral data were collected via 1:1 or self-administered computerized interviews. Adjusted individual-study, multivariable relative risk regression was used to examine the relationship between CS and SU. We also examined interactions with type of sex and partner HIV status. Pooled effect estimates were calculated using traditional fixed-effects meta-analysis. We analyzed data for recent SU (n = 6781; 82% men, median age = 33 years) and SU before/during sex (n = 2915; 69% men, median age = 40 years). Results For both exposure classifications, any SU other than cannabis increased the likelihood of CS relative to non-SU (8–16%, p-valuesp p p p = 0.002). Single- and poly-SU before/during sex increased the likelihood of CS for those with exclusively HIV-negative partners (7–8%, p ≤ 0.02), and for those reporting HIV-negative and HIV-status unknown partners (9–13%, p ≤ 0.03). Conclusion Except for cannabis, any SU increased the likelihood of CS. CS was associated with having perceived HIV-negative partners and with having had both anal/vaginal sex.

HIV disclosure is an important behavior with implications for HIV treatment and prevention but understudied among new to HIV care patients who face unique challenges adjusting to a new diagnosis. This study evaluated the factors associated with HIV disclosure status and patterns of HIV disclosure among new to HIV care patients. A cross-sectional study was conducted evaluating the iENGAGE (integrating ENGagement and Adherence Goals upon Entry) cohort. Participants were enrolled in this randomized behavioral trial between December 2013 and June 2016. The primary and secondary outcomes included HIV disclosure status (Yes/No) and patterns of disclosure (Broad, Selective and Nondisclosure), respectively. Logistic and Multinomial Logistic Regression were used to evaluate the association of participant factors with HIV disclosure and patterns of HIV disclosure, respectively. Of 371 participants, the average age was 37 ± 12 years, 79.3% were males, and 62.3% were African Americans. A majority of participants (78.4%) disclosed their HIV status at baseline, 63.1% were broad disclosers and 15.2% were selective disclosers. In multivariable regression, black race, emotional support, and unmet needs predicted any HIV and broad disclosure, whereas males, emotional support, active coping, and acceptance were associated with selective disclosure. Interventions to promote early disclosure should focus on coping strategies and unmet needs, particularly among black and male people living with HIV initiating care.

Author(s): Bourgi, Kassem; Jenkins, Cathy A; Rebeiro, Peter F; Palella, Frank; Moore, Richard D; Altoff, Keri N; Gill, John; Rabkin, Charles S; Gange, Stephen J; Horberg, Michael A; Margolick, Joseph; Li, Jun; Wong, Cherise; Willig, Amanda; Lima, Viviane D; Crane, Heidi; Thorne, Jennifer; Silverberg, Michael; Kirk, Gregory; Mathews, William C; Sterling, Timothy R; Lake, Jordan; Koethe, John R; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) | Abstract: IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naive PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naive PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with g10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of g10% body weight increase at two years (adjusted odds ration=n1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.

BackgroundAnemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking.MethodsWithin a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010–3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin ResultsThis retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range [IQR] 4.3–7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR.ConclusionBecause anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.

Despite its potential to improve metabolic health outcomes, longitudinal physical activity (PA) patterns and their association with cardiometabolic disease among people living with HIV (PLWH) have not been well characterized. We investigated this relationship among PLWH in the Centers for AIDS Research Network of Integrated Clinical Systems with at least one PA self-report between 2008 and 2015. The 4-item Lipid Research Clinics PA instrument was used to categorize habitual PA levels as: Very Low, Low, Moderate, or High. We analyzed demographic differences in PA patterns. Multivariable generalized estimating equation regression models were fit to assess longitudinal associations of PA with blood pressure, lipid, and glucose levels. Logistic regression modeling was used to assess the odds of being diagnosed with obesity, cardiovascular disease (CVD), cerebrovascular disease, hypertension, diabetes, or multimorbidity. A total of 40,462 unique PA assessments were provided by 11,719 participants. Only 13% of PLWH reported High PA, while 68% reported Very Low/Low PA at baseline and did not increase PA levels during the study period. Compared to those reporting High PA, participants with Very Low PA had almost 2-fold increased risk for CVD. Very Low PA was also associated with several risk factors associated with CVD, most notably elevated triglycerides (odds ratio 25.4), obesity (odds ratio 1.9), hypertension (odds ratio 1.4), and diabetes (odds ratio 2.3; all p&nbsp

INTRODUCTION: Despite the issuance of evidence-based and evidence–informed guidelines to improve engagement in HIV care and adherence-related outcomes, few studies have assessed contemporary adherence or engagement support practices of HIV care providers in US clinics. As a result, the standard of HIV care in the US and globally remains poorly understood. OBJECTIVE: This programmatic assessment approach aimed to identify the strengths and gaps in the current standard of HIV care from the perspective of HIV care providers. METHODS: A self-administered Standard of Care measure was developed and delivered through Qualtrics to HIV care providers at four different HIV care sites as a part of a multisite intervention study to improve engagement in HIV care and ART adherence. Providers were asked to provide demographic and clinic specific information, identify practices/strategies applied during typical initial visits with HIV-positive patients and visits prior to and at ART initiation, as well as their perceptions of patient behaviors and adequacy of HIV care services at their clinics. RESULTS: Of the 75 surveys which were completed, the majority of respondents were physicians, and on average, providers have worked in HIV care for 13.5 years. Across the sites, 91% of the providers’ patient panels consist of HIV-positive patients, the majority of whom are virally suppressed and 1/5 are considered “out of care.” Few resources were routinely available to providers by other staff related to monitoring patient adherence and engagement in care. During typical initial visits with HIV positive patients, the majority of providers report discussing topics focused on behavioral/life contexts such as sexual partnerships, sexual orientation, disclosure, and other sources of social support. Nearly all providers emphasize the importance of adherence to treatment recommendations and nearly 90% discuss outcomes of good adherence and managing common side effects during ART start visits. Overall, providers do not report often implementing practices to improve retention in care. CONCLUSIONS: Survey results point to opportunities to enhance engagement in HIV care and improve ART adherence through systematic data monitoring and increased collaboration across providers and other clinic staff, specifically when identifying patients defined as “in need” or “out of care.”

Symptom distress remains a challenging aspect of living with HIV. Physical activity is a promising symptom management strategy, but its effect on symptom distress has not been examined in a large, longitudinal HIV-infected cohort. We hypothesized that higher physical activity intensity would be associated with reduced symptom distress. We included 5,370 people living with HIV (PLHIV) who completed patient-reported assessments of symptom distress, physical activity, alcohol and substance use, and HIV medication adherence between 2005 and 2016. The most frequent and burdensome symptoms were fatigue (reported by 56%), insomnia (50%), pain (46%), sadness (45%), and anxiety (45%), with women experiencing more symptoms and more burdensome symptoms than men. After adjusting for age, sex, race, time, HIV medication adherence, alcohol and substance use, site, and HIV RNA, greater physical activity intensity was associated with lower symptom intensity. Although individual symptoms may be a barrier to physical activity (e.g. pain), the consistent association between symptoms with physical activity suggests that more intense physical activity could mitigate symptoms experienced by PLHIV.

We examined adherence, medication-taking practices, and preferences to inform development of a wrist-worn adherence system. Two convenience samples of persons taking antiretroviral therapy and HIV pre-exposure prophylaxis completed a survey. Additional online questions asked about willingness to use a wrist-worn device and reminder and feedback preferences. Among 225 participants, 13% reported adherence < 90% this was associated with younger age and clinic sample. Compared to pill bottle–using participants, mediset users less commonly reported adherence < 90% (aOR = 0.16, p = .02), and blister pack users (aOR = 6.3, p = .02) and pill roll users (aOR = 3.3, p = .04) more commonly reported adherence < 90%. Sixty-two percent of the online participants reporting adherence (< 100%) had some interest in receiving adherence reminders, including 42% with interest in receiving reminders by smartwatch notifications. Although confounders are likely, formative work identified potential users and interest in using a wrist-worn adherence system. Future work will determine its acceptability and efficacy.

INTRODUCTION: Few studies examine how depression and substance use interact to affect HIV control. METHODS: In 14,380 persons with HIV (PWH), we used logistic regression and generalized estimating equations to evaluate how symptoms of depression interact with alcohol, cocaine, opioid, and methamphetamine use to affect subsequent retention in care, maintaining an active prescription for ART, and consistent virologic suppression. RESULTS: Among PWH with no or mild depressive symptoms, heavy alcohol use had no association with virologic suppression (OR 1.00 [0.95–1.06]); among those with moderate or severe symptoms, it was associated with reduced viral suppression (OR 0.80 [0.74–0.87]). We found no interactions with heavy alcohol use on retention in care or maintaining ART prescription or with other substances for any outcome. DISCUSSION: These results highlight the importance of treating moderate or severe depression in PWH, especially with comorbid heavy alcohol use, and support multifaceted interventions targeting alcohol use and depression.

Background The United States National HIV/AIDS Strategy established goals to reduce disparities in retention in human immunodeficiency virus (HIV) care, antiretroviral therapy (ART) use, and viral suppression. The impact of sex, age, and sexual HIV acquisition risk (ie, heterosexual vs same-sex contact) on the magnitude of HIV-related racial/ethnic disparities is not well understood. Methods We estimated age-stratified racial/ethnic differences in the 5-year restricted mean percentage of person-time spent in care, on ART, and virally suppressed among 19 521 women (21.4%), men who have sex with men (MSM; 59.0%), and men who have sex with women (MSW; 19.6%) entering HIV care in the North American AIDS Cohort Collaboration on Research and Design between 2004 and 2014. Results Among women aged 18-29 years, whites spent 12.0% (95% confidence interval [CI], 1.1%-20.2%), 9.2% (95% CI, .4%-20.4%), and 13.5% (95% CI, 2.7%-22.5%) less person-time in care, on ART, and virally suppressed, respectively, than Hispanics. Black MSM aged ≥50 years spent 6.3% (95% CI, 1.3%-11.7%), 11.0% (95% CI, 4.6%-18.1%), and 9.7% (95% CI, 3.6%-16.8%) less person-time in these stages, respectively, than white MSM ≥50 years of age. Among MSM aged 40-49 years, blacks spent 9.8% (95% CI, 2.4%-16.5%) and 11.9% (95% CI, 3.8%-19.3%) less person-time on ART and virally suppressed, respectively, than whites. Conclusions Racial/ethnic differences in HIV care persist in specific populations defined by sex, age, and sexual HIV acquisition risk. Clinical and public health interventions that jointly target these demographic factors are needed.

Missed HIV medical visits predict poor clinical outcomes. We sought to identify patients at high risk of missing visits. We analyzed 2002-2014 data from six large US HIV clinics. At each visit, we predicted the likelihood of missing the next scheduled visit using demographic, clinical, and patient-reported psychosocial variables. Overall, 10,374 participants contributed 105,628 HIV visits. For 17% of visits, the next scheduled appointment was missed. The strongest predictor of a future missed visit was past-year missed visits. A model with only this predictor had area under the receiver operator curve = 0.65; defining "high risk" as those with any past-year missed visits had 73% sensitivity and 51% specificity in correctly identifying a future missed visit. Inclusion of other clinical and psychosocial predictors only slightly improved performance. Past visit attendance can identify those at increased risk for future missed visits, allowing for proactive allocation of resources to those at greatest risk.

Cigarette smoking is particularly harmful for sexual minority men living with HIV. This study aimed to find benefits of quitting by examining relationships between smoking and sustained HIV RNA suppression, recent CD4 count, ART medication adherence, and engagement in HIV medical care. Sexual minority men (n = 346), former or current smokers, received HIV care at a community health center. Survey responses were combined with electronic health record data in adjusted regression models. Most patients were Caucasian (87%) and 148 (46%) had incomes below the poverty level and 80% had sustained HIV RNA suppression. Compared to current smokers, former smokers had increased odds of sustaining HIV RNA suppression (OR 1.89; 95% CI 1.02–3.48) of reporting > 90% adherence (OR 2.25; 95% CI 1.21–4.17), and were less likely to miss appointments (OR 0.37; 95% CI 0.17–0.82). Heavier smokers (OR 0.36; 95% CI 0.17–0.77) and patients who smoked the longest (OR 0.31; 95% CI 0.14–0.68) had reduced odds of sustaining HIV RNA suppression. Smoking assessment, treatment, and referral could augment HIV outcomes for sexual minority men with HIV.

BACKGROUND: Age-associated conditions are increasingly common among persons living with human immunodeficiency virus (HIV) (PLWH). A longitudinal investigation of their accrual is needed given their implications on clinical care complexity. We examined trends in the co-occurrence of age-associated conditions among PLWH receiving clinical care, and differences in their prevalence by demographic subgroup. METHODS: This cohort study was nested within the North American AIDS Cohort Collaboration on Research and Design. Participants from HIV outpatient clinics were antiretroviral therapy–exposed PLWH receiving clinical care (ie, ≥1 CD4 count) in the United States during 2000–2009. Multimorbidity was irreversible, defined as having ≥2: hypertension, diabetes mellitus, chronic kidney disease, hypercholesterolemia, end-stage liver disease, or non–AIDS-related cancer. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) comparing demographic subgroups were obtained by Poisson regression with robust error variance, using generalized estimating equations for repeated measures. RESULTS: Among 22969 adults, 79% were male, 36% were black, and the median baseline age was 40 years (interquartile range, 34–46 years). Between 2000 and 2009, multimorbidity prevalence increased from 8.2% to 22.4% (P(trend) < .001). Adjusting for age, this trend was still significant (P < .001). There was no difference by sex, but blacks were less likely than whites to have multimorbidity (aPR, 0.87; 95% CI, .77–.99). Multimorbidity was the highest among heterosexuals, relative to men who have sex with men (aPR, 1.16; 95% CI, 1.01–1.34). Hypertension and hypercholesterolemia most commonly co-occurred. CONCLUSIONS: Multimorbidity prevalence has increased among PLWH. Comorbidity prevention and multisubspecialty management of increasingly complex healthcare needs will be vital to ensuring that they receive needed care.

In the United States, little is known about interventions that rely on mobile phones and/or text messaging to improve engagement in HIV care for vulnerable populations. Domestic studies using these technologies as part of the National Institute on Drug Abuse "Seek, Test, Treat, Retain" research initiative were queried regarding intervention components, implementation issues, participant characteristics, and descriptive statistics of mobile phone service delivery. Across five studies with 1,135 predominantly male, minority participants, implementation challenges occurred in three categories: (1) service interruptions; (2) billing/overage issues, and; (3) the participant user experience. Response rules for automated text messages frequently frustrated participants. The inability to reload minutes/texting capacity remotely was a significant barrier to intervention delivery. No study encountered confidentiality breaches. Service interruption was common, even if studies provided mobile phones and plans. Future studies should attend to the type of mobile phone and service, the participant user experience, and human subjects concerns.

Summary Background Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. Methods In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3–6 months (when below the threshold) or every 9–12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. Findings 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86–1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95–1·22) for threshold 200 and 1·03 (0·96–1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17–3·43) for threshold 200 and 1·24 (0·89–1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (−25·5 to 26·3) cells per μL for threshold 200 and −3·5 (−16·0 to 8·9) cells per μL for threshold 350. Interpretation Decreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies. Funding National Institutes of Health.

Objective The aim of this study was to assess whether ever reporting depressive symptoms affects mortality in the modern HIV treatment era. Design A cohort study of HIV-infected adults in routine clinical care at seven sites in the USA. Methods We examined the effect of ever reporting depressive symptoms on all-cause mortality using data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort. We included individuals with at least one depression measure between 2005 and 2014. Depressive symptoms were measured with the Patient Health Questionnaire (PHQ)-9. We used weighted Kaplan-Meier curves and marginal structural Cox models with inverse probability weights to estimate the effect of ever reporting depressive symptoms (PHQ-9 ≥10) on all-cause mortality. Results A total of 10 895 individuals were included. Participants were followed for a median of 3.1 years (35 621 total person-years). There were 491 (4.5%) deaths during the follow-up period (crude incidence rate 13.8/1000 person-years). At baseline, 28% of the population reported depressive symptoms. In the weighted analysis, there was no evidence that ever reporting depressive symptoms increased the hazard of all-cause mortality (hazard ratio 0.82, 95% confidence interval 0.55-1.24). Conclusion In a large cohort of HIV-infected adults in care in the modern treatment era, we observed no evidence that ever reporting depressive symptoms increased the likelihood of all-cause mortality, controlling for a range of time-varying factors. Antiretroviral therapy that is increasingly robust to moderate adherence and improved access to depression treatment may help to explain changes in the relationship between depressive symptoms and mortality in the modern treatment era.

Hazardous alcohol use is associated with detrimental health outcomes among persons living with HIV (PLWH). We examined the prevalence and factors associated with hazardous alcohol use in the current era using several hazardous drinking definitions and binge drinking defined as ≥5 drinks for men versus ≥4 for women. We included 8567 PLWH from 7 U.S. sites from 2013 to 2015. Current hazardous alcohol use was reported by 27% and 34% reported binge drinking. In adjusted analyses, current and past cocaine/crack (odd ratio [OR] 4.1:3.3–5.1, p < 0.001 and OR 1.3:1.1–1.5, p < 0.001 respectively), marijuana (OR 2.5:2.2–2.9, p < 0.001 and OR 1.4:1.2–1.6, p < 0.001), and cigarette use (OR 1.4:1.2–1.6, p < 0.001 and OR 1.3:1.2–1.5, p < 0.001) were associated with increased hazardous alcohol use. The prevalence of hazardous alcohol use remains high in the current era, particularly among younger men. Routine screening and targeted interventions for hazardous alcohol use, potentially bundled with interventions for other drugs, remain a key aspect of HIV care.

Background Providers are often unaware of poor adherence to prescribed medications for their patients with chronic diseases. Objective To develop brief, computer-administered patient-reported measures in English and Spanish assessing adherence behaviors and barriers. Design, Participants, and Main Measures: Item pools were constructed from existing measures of medication adherence behaviors and barriers, which informed development of a patient concept elicitation interview guide to identify medication adherence behavior and barrier-related concepts. Two hundred six patients either living with HIV (PLWH) or without were interviewed. Interviews were coded, concepts matched to item pool content, and new items were developed for novel concepts. A provider/investigator team highlighted clinically relevant items. Cognitive interviews were conducted with patients on final candidate items (n = 37). The instruments were administered to 2081 PLWH. Key results Behavioral themes from concept elicitation interviews included routines incorporating time of day, placement, visual cues, and intentionality to miss or skip doses. Barrier themes included health-related (e.g. depressed mood, feeling ill), attitudes/beliefs (e.g., need for medication), access (e.g., cost/insurance problems), and circumstantial barriers (e.g., lack of privacy, disruption of daily routine). The final instruments included 6 behavior items, and 1 barrier item with up to 23 response options. PLWH endorsed a mean (SD) of 3.5 (1.1) behaviors. The 201 PLWH who missed ≥2 doses in the previous week endorsed a mean (SD) of 3.1 (2.5) barriers. The intraclass correlation coefficient (ICC) for the numbers of behaviors endorsed in 61 PLWH after 4–16 days was 0.54 and for the number of barriers for the 20 PLWH with ≥2 missed doses the ICC was 0.89, representing fair and excellent test-retest reliability. Conclusion Measures of medication adherence behaviors and barriers were developed for use with patients living with chronic diseases focusing on clinical relevance, brevity, and content validity for use in clinical care.

BACKGROUND: Guidelines for initial antiretroviral treatment (ART) regimens have evolved, with integrase strand transfer inhibitors (INSTI) increasingly prominent. Research on virologic failure (VF) with INSTI therapy is predominantly from clinical trials not care settings, especially for recently approved medications including dolutegravir. We compared outcomes among people living with HIV (PLWH) who initiated recommended regimens in clinical care across the United States. SETTING: We examined two groups of PLWH at eight clinics who initiated ART regimens (August 1, 2013–March 31, 2017): those ART treatment-naive at initiation, and those treatment-experienced. METHODS: The outcome in this longitudinal cohort study was VF, defined as a viral load of ≥400 copies/mL ≥6 months after ART initiation. We examined the proportion of individuals who remained on, switched, or discontinued the regimen. Associations between regimens and outcomes were examined with adjusted Cox proportional hazards models. RESULTS: Among 5177 PLWH, a lower proportion experienced VF on dolutegravir- versus other INSTI- or darunavir-based regimens for previously treatment-naive (7% vs. 12% vs. 28%) and treatment-experienced PLWH (6% vs. 10% vs. 21%). In adjusted analyses, hazard ratios (HRs) were similar across regimens for the combined outcome of regimen discontinuation or treatment switch. The HR for VF comparing dolutegravir- to darunavir-based regimens was 0.30 (95%CI:0.2–0.6) among previously treatment-naive PLWH and was 0.60 (95%CI:0.4–0.8) among treatment-experienced PLWH. CONCLUSIONS: The proportion of previously treatment-naïve PLWH remaining on recommended ART regimens did not differ by regimen. The likelihood of VF was lower with dolutegravir- than darunavir-based regimens for previously treatment-naïve and treatment-experienced PLWH.

Objective: Bilirubin is an antioxidant that may suppress lipid oxidation. Elevated bilirubin is associated with decreased cardiovascular events in HIV-uninfected populations. We examined these associations in people living with HIV (PLWH). Methods: Potential myocardial infarctions (MIs) and strokes were centrally adjudicated. We examined MI types: type 1 MI (T1MI) from atherosclerotic plaque instability and type 2 MI (T2MI) in the setting of oxygen demand/supply mismatch such as sepsis. We used multivariable Cox regression analyses to determine associations between total bilirubin levels and outcomes adjusting for traditional and HIV-specific risk factors. To minimize confounding by hepatobiliary disease, we conducted analyses limited to bilirubin values

Background Persons with human immunodeficiency virus (HIV) have higher risks for myocardial infarction (MI) than the general population. This is driven in part by higher type 2 MI (T2MI, due to coronary supply-demand mismatch) rates among persons with HIV (PWH). In the general population, T2MI has higher mortality than type 1 MI (T1MI, spontaneous and generally due to plaque rupture and thrombosis). PWH have a greater burden of comorbidities and may therefore have an even greater excess risk for complication and death in the setting of T2MI. However, mortality patterns after T1MI and T2MI in HIV are unknown. Methods We analyzed mortality after MI among PWH enrolled in the multicenter, US-based Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort (N = 28,186). Incident MIs occurring between January 1, 1996, and December 31, 2014, were centrally adjudicated and classified as T1MI or T2MI. We first compared mortality following T1MI vs. T2MI among PWH. Cox survival analyses and Bayesian model averaging were then used to evaluate pre-MI covariates associated with mortality following T1MI and T2MI. Results Among the 596 out of 28,186 PWH who experienced MI (2.1%; 293 T1MI and 303 T2MI), mortality rates were significantly greater after T2MI (22.2/100 person-years; 1-, 3-, and 5-year mortality 39%, 52%, and 62%) than T1MI (8.2/100 person-years; 1-, 3-, and 5-year mortality 15%, 22%, and 30%). Significant mortality predictors after T1MI were higher HIV viral load, renal dysfunction, and older age. Significant predictors of mortality after T2MI were low body-mass index (BMI) and detectable HIV viral load. Conclusions Mortality is high following MI for PWH and substantially greater after T2MI than T1MI. Predictors of death after MI differed by type of MI, reinforcing the different clinical scenarios associated with each MI type and the importance of considering MI types separately. Electronic supplementary material The online version of this article (10.1186/s12916-019-1385-7) contains supplementary material, which is available to authorized users.

Entering HIV care is a vulnerable time for newly diagnosed individuals that necessitates frequent medical visits and initiation of life-long antiretroviral therapy (ART). At this time, there is potential to exacerbate psychosocial difficulties, such as depression and stigma. These psychosocial difficulties contribute to poor health-related quality of life (HRQOL) that in turn, may influence health behaviors including ART adherence, the driver of viral suppression. Understanding HRQOL in people newly entering HIV care is critical and has the potential to guide practice and research. This exploratory cross-sectional study examined demographic, clinical, and psychosocial factors associated with limitations in four specific domains of HRQOL (mobility, usual activities, pain, and depression/anxiety or mood) among persons initially entering outpatient HIV care at four sites in the United States (n = 335). In the unadjusted analysis, female gender was significantly associated with sub-optimal HRQOL with women having increased odds of reporting HRQOL challenges with pain, mood, mobility, and usual activity when compared to men. The adjusted models demonstrated attenuation of parameter estimates and loss of statistical significance for the associations with impaired HRQOL observed among women in unadjusted analyses, suggesting psychosocial factors related to HRQOL are complex and interrelated. Findings are consistent with a robust literature documenting gender-related health disparities. Programs aimed at improving HRQOL for persons initially entering HIV care are warranted generally, and specifically for women, and must address modifiable psychosocial factors such as stigma, via mechanisms including coping and social support.

Among people with HIV, alcohol use is associated with increased prevalence of sexual transmission behaviors. We examined associations between alcohol use in the prior year and sexual behaviors approximately six months later among 1857 women, 6752 men who have sex with men (MSM) and 2685 men who have sex with women (MSW). Any alcohol use was associated with increased risk of unsafe vaginal sex among women; anal sex and =>2 anal sex partners among MSM; and anal sex, =>2 anal or vaginal sex partners, and unsafe vaginal sex among MSW. In particular, among women >7 alcoholic drinks/week and among MSW =>5 alcoholic drinks/drinking day increased the likelihood of certain subsequent sexual behaviors. For all groups, especially women, the risk of sex under the influence of drugs/alcohol markedly increased with increases in quantity and frequency of alcohol consumption. These different patterns of drinking and sexual behaviors indicate the importance of tailored counseling messages to women, MSM and MSW.

Background People living with HIV ( PLWH ) have an increased risk of myocardial infarction ( MI ). Changes in the gut microbiota that occur with chronic HIV infection could play a role in HIV ‐associated atherosclerosis. Choline, carnitine, betaine, and trimethylamine N‐oxide are small molecules that are, in part, metabolized or produced by the gut microbiome. We hypothesized that these metabolites would be associated with carotid artery intima‐media thickness and MI in PLWH . Methods and Results Carotid artery intima‐media thickness was measured at baseline and at a median interval of 4 years in 162 PLWH from the SCOPE (Study of the Consequences of the Protease Inhibitor Era) cohort in San Francisco, CA . Separately, 105 PLWH (36 cases with type I adjudicated MI and 69 controls without MI ) were selected from the Center for AIDS Research Network of Integrated Clinical Systems, a multicenter clinic‐based cohort. Controls were matched by demographics, CD 4 cell count, and duration of viral suppression. In the SCOPE cohort, higher carnitine levels had a significant association with presence of carotid plaque and greater baseline and progression of mean carotid artery intima‐media thickness after adjusting for traditional cardiovascular disease risk factors. In the treated and suppressed subgroup, these associations with carnitine remained significant after adjustment for cardiovascular disease risk factors. In the Center for AIDS Research Network of Integrated Clinical Systems cohort, the risk of MI was significantly increased in subjects with carnitine levels in the highest quartile after adjustment for cardiovascular disease risk factors. Conclusions In PLWH , including the treated and suppressed subgroup, carnitine is independently associated with carotid artery intima‐media thickness, carotid plaque, and MI in 2 separate cohorts. These results emphasize the potential role of gut microbiota in HIV ‐associated atherosclerosis and MI , especially in relation to carnitine metabolism.

BackgroundResearch is needed to better understand relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma, a common cancer in people living with HIV. We aimed to identify key CD4 count and HIV RNA (viral load) predictors of risk for non-Hodgkin lymphoma, overall and by subtype.MethodsWe studied people living with HIV during 1996-2014 from 21 Canadian and US cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. To determine key independent predictors of risk for non-Hodgkin lymphoma, we assessed associations with time-updated recent, past, cumulative, and nadir or peak measures of CD4 count and viral load, using demographics-adjusted, cohort-stratified Cox models, and we compared models using Akaike's information criterion.FindingsOf 102 131 people living with HIV during the study period, 712 people developed non-Hodgkin lymphoma. The key independent predictors of risk for overall non-Hodgkin lymphoma were recent CD4 count (ie, lagged by 6 months