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BackgroundPeople with HIV (PWH) are at increased risk of cardiovascular comorbidities and substance use is a potential predisposing factor. We evaluated associations of tobacco smoking and alcohol use with venous thromboembolism (VTE) in PWH.MethodsWe assessed incident, centrally adjudicated VTE among 12 957 PWH within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between January 2009 and December 2018. Using separate Cox proportional hazards models, we evaluated associations of time-updated alcohol and cigarette use with VTE, adjusting for demographic and clinical characteristics. Smoking was evaluated as pack-years and never, former, or current use with current cigarettes per day. Alcohol use was parameterized using categorical and continuous alcohol use score, frequency of use, and binge frequency.ResultsDuring a median of 3.6 years of follow-up, 213 PWH developed a VTE. One-third of PWH reported binge drinking and 40% reported currently smoking. In adjusted analyses, risk of VTE was increased among both current (HR: 1.44, 95% CI: 1.02-2.03) and former (HR: 1.44, 95% CI: 0.99-2.07) smokers compared to PWH who never smoked. Additionally, total pack-years among ever-smokers (HR: 1.10 per 5 pack-years; 95% CI: 1.03-1.18) was associated with incident VTE in a dose-dependent manner. Frequency of binge drinking was associated with incident VTE (HR: 1.30 per 7 days/month, 95% CI: 1.11-1.52); however, alcohol use frequency was not. Severity of alcohol use was not significantly associated with VTE.ConclusionsCurrent smoking and pack-year smoking history were dose-dependently associated with incident VTE among PWH in CNICS. Binge drinking was also associated with VTE. Interventions for smoking and binge drinking may decrease VTE risk among PWH.

Among 14 049 people with human immunodeficiency virus in care in 2019-2020, 96% were treated with antiretroviral therapy (ART). Current antiretroviral treatment patterns highlight high uptake of guideline-recommended ART regimens including second-generation integrase strand transfer inhibitors (dolutegravir and bictegravir) and tenofovir alafenamide, especially in antiretroviral-naive individuals initiating ART.

BackgroundUnderstanding the spectrum of COVID-19 in people with HIV (PWH) is critical to provide clinical guidance and risk reduction strategies.SettingCenters for AIDS Research Network of Integrated Clinic System, a US multisite clinical cohort of PWH in care.MethodsWe identified COVID-19 cases and severity (hospitalization, intensive care, and death) in a large, diverse HIV cohort during March 1, 2020-December 31, 2020. We determined predictors and relative risks of hospitalization among PWH with COVID-19, adjusted for disease risk scores.ResultsOf 16,056 PWH in care, 649 were diagnosed with COVID-19 between March and December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized, and 12 died. PWH with current CD4 count

ObjectivesTo define the incidence of clinically detected coronavirus disease 2019 (COVID-19) in people with HIV (PWH) in the United States and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19.DesignObservational study within the CFAR Network of Integrated Clinical Systems cohort in seven cities during 2020.MethodsWe calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4+ cell count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores.ResultsAmong 16 056 PWH in care, of whom 44.5% were black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4+ cell count less than 350 cells/μl, including 7% less than 200; 95.5% were on antiretroviral therapy (ART), and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and black PWH respectively, than non-Hispanic white PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or black identity, lowest historical CD4+ cell count less than 350 cells/μl (proxy for CD4+ nadir), current low CD4+ : CD8+ ratio, diabetes, and obesity.ConclusionOur results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWH. PWH with immune exhaustion as evidenced by lowest historical CD4+ cell count or current low CD4+ : CD8+ ratio had greater risk of COVID-19.

To assess atrial fibrillation risk factors in people with HIV, we identified incident atrial fibrillation in a large clinical cohort of people receiving care. Compared with 970 controls without atrial fibrillation, the 97 with adjudicated incident atrial fibrillation were older, less likely Hispanic, and had more coronary disease, heart failure, and chronic obstructive pulmonary disease. In multivariable analysis, nonuse of antiretroviral therapy and prescription of antiretroviral regimens with multiple core agents were associated with increased atrial fibrillation risk.

BackgroundInsomnia is common among people with HIV (PWH) and may be associated with increased risk of myocardial infarction (MI). This study examines the association between insomnia and MI by MI type among PWH.SettingLongitudinal cohort study of PWH at 5 Centers for AIDS Research Network of Integrated Clinical Systems sites.MethodsClinical data and patient-reported measures and outcomes from PWH in care between 2005 and 2018 were used in this study. Insomnia, measured at baseline, was defined as having difficulty falling or staying asleep with bothersome symptoms. The Centers for AIDS Research Network of Integrated Clinical Systems centrally adjudicates MIs using expert reviewers, with distinction between type 1 MI (T1MI) and type 2 MI (T2MI). Associations between insomnia and first incident MI by MI type were measured using separate Cox proportional hazard models adjusted for age, sex, race/ethnicity, traditional cardiovascular disease risk factors (hypertension, dyslipidemia, poor kidney function, diabetes, and smoking), HIV markers (antiretroviral therapy, viral suppression, and CD4 cell count), and stimulant use (cocaine/crack and methamphetamine).ResultsAmong 12,448 PWH, 48% reported insomnia. Over a median of 4.4 years of follow-up, 158 T1MIs and 109 T2MIs were identified; approximately half of T2MIs were attributed to sepsis or stimulant use. After adjustment for potential confounders, we found no association between insomnia and T1MI (hazard ratio = 1.05, 95% confidence interval: 0.76 to 1.45) and a 65% increased risk of T2MI among PWH reporting insomnia compared with PWH without insomnia (hazard ratio = 1.65, 95% confidence interval: 1.11 to 2.45).ConclusionsPWH reporting insomnia are at an increased risk of T2MI, but not T1MI, compared with PWH without insomnia, highlighting the importance of distinguishing MI types among PWH.

Abstract: Background: Little is known about how race and ethnicity, imperfect (albeit accessible) proxies for structural racism, impact COVID-19 incidence among people with HIV (PWH). We report the cumulative incidence and incidence rate ratios (IRR) for COVID-19 in a long-term multi-site cohort of PWH across the US Figure 1. Cumulative incidence of COVID-19 in the CNICS cohort Methods: We examined COVID-19 cumulative incidence and IRR among PWH in care between 3/1/2020 and 12/31/2020 at seven sites in the CFAR Network of Integrated Clinical Systems (CNICS) cohort. We define COVID-19 incident case as having a laboratory-confirmed (RT-PCR/Ag) SARS-CoV-2 positive result or diagnosis verified by chart review. Reinfections were excluded. Results are presented as monthly and quarterly cumulative incidence and IRR with 95% CI stratified by CD4 count, self-reported race/ethnicity, and site. Follow-up was censored on the earliest of diagnosis of COVID-19 disease, loss to follow up, or 12/31/2020 Results: Among 15,780 PWH in care in the CNICS cohort during the study period, 62% were non-white, with a median (IQR) age of 52 (IQR 40-59), 95% were on antiretroviral therapy, 17% had a CD4 count less than 350, and 6% less than 200. Overall, 651 PWH tested positive for COVID-19 for a cumulative incidence of 4.13%. COVID-19 cumulative incidence increased from 0.77% at the end of the first quarter to 4.12% by the end of December 2020. At the peak of the pandemic in December 2020, the cumulative incidence in Black PWH was 1.68 fold higher than in white PWH (p=.033) and 2.35 fold higher in Hispanics than in whites (P< .0001), figure 1. Similarly, the IRR for COVID-19 was 1.71 (95% CI 1.42-2.07) for Black and 2.40 (95% CI 1.91-3.01) for Hispanic PWH relative to white. Although there was variation across sites, reflecting geographic differences in pandemic waves and access to COVID-19 testing, overall individual trends remained the same. COVID-19 cumulative incidence was similar across CD4 cell count strata Conclusion: Our results suggest effects of structural racial disparities on COVID-19 incidence in this diverse population of PWH across the US, with higher and disproportionate rates of COVID-19 in Black and Hispanic PWH. Incidence estimates are conservative because testing was not uniform, and no systematic testing was conducted Disclosures: Edward R. Cachay, MD, MAS, Gilead Science (Grant/Research Support, Advisor or Review Panel member)Merck Sharp & Dohme Corp (Grant/Research Support) Adrienne Shapiro, MD, PhD, Vir Biotechnology (Scientific Research Study Investigator) Darcy Wooten, MD, MS, Nothing to disclose Rachel A. Bender Ignacio, MD MPH, Abbvie (Individual(s) Involved: Self): Consultant; SeaGen (Individual(s) Involved: Self): Consultant Greer A. Burkholder, MD, MSPH, Eli Lilly (Grant/Research Support) Heidi Crane, MD, MPH, ViiV (Grant/Research Support)

Substance use in the U.S. varies by geographic region. Opioid prescribing practices and marijuana, heroin, and methamphetamine availability are evolving differently across regions. We examined self-reported substance use among people living with HIV (PLWH) in care at seven sites from 2017-2019 to understand current regional substance use patterns. We calculated the percentage and standardized percentage of PLWH reporting current drug use and at-risk and binge alcohol use by U.S. Census Bureau geographic region and examined associations in adjusted logistic regression analyses. Among 7,686 PLWH, marijuana use was the most prevalent drug (30%), followed by methamphetamine/crystal (8%), cocaine/crack (7%), and illicit opioids (3%). One-third reported binge alcohol use (32%). Differences in percent of current use by region were seen for marijuana (24-41%) and methamphetamine/crystal (2-15%), with more use in the West and Northeast, and binge alcohol use (26-40%). In adjusted analyses, PLWH in the Midwest were significantly less likely to use methamphetamine/crystal (aOR: 0.13;0.06-0.25) or illicit opioids (aOR:0.16;0.05-0.53), and PLWH in the Northeast were more likely to use cocaine/crack (aOR:1.59;1.16-2.17), compared to PLWH in the West. Understanding differences in substance use patterns in the current era, as policies continue to evolve, will enable more targeted interventions in clinical settings among PLWH.

BackgroundInformation regarding the impact of substance use on the timing of entry into HIV care is lacking. Better understanding of this relationship can help guide approaches and policies to improve HIV testing and linkage.MethodsWe examined the effect of specific substances on stage of HIV disease at entry into care in over 5000 persons with HIV (PWH) newly enrolling in care. Substance use was obtained from the AUDIT-C and ASSIST instruments. We examined the association between early entry into care and substance use (high-risk alcohol, methamphetamine, cocaine/crack, illicit opioids, marijuana) using logistic and relative risk regression models adjusting for demographic factors, mental health symptoms and diagnoses, and clinical site.ResultsWe found that current methamphetamine use, past and current cocaine and marijuana use was associated with earlier entry into care compared with individuals who reported no use of these substances.ConclusionEarly entry into care among those with substance use suggests that HIV testing may be differentially offered to people with known HIV risk factors, and that individuals with substances use disorders may be more likely to be tested and linked to care due to increased interactions with the healthcare system.

BackgroundRates of stroke are higher in people living with HIV compared with age-matched uninfected individuals. Causes of elevated stroke risk, including the role of viremia, are poorly defined.MethodsBetween 1 January 2006 and 31 December 2014, we identified incident strokes among people living with HIV on antiretroviral therapy at five sites across the United States. We considered three parameterizations of viral load (VL) including (1) baseline (most recent VL before study entry), (2) time-updated, and (3) cumulative VL (copy-days/mL of virus). We used Cox proportional hazards models to estimate hazard ratios (HRs) for stroke risk comparing the 75th percentile ("high VL") to the 25th percentile ("low VL") of baseline and time-updated VL. We used marginal structural Cox models, with most models adjusted for traditional stroke risk factors, to estimate HRs for stroke associated with cumulative VL.ResultsAmong 15,974 people living with HIV, 139 experienced a stroke (113 ischemic; 18 hemorrhagic; eight were unknown type) over a median follow-up of 4.2 years. Median baseline VL was 38 copies/mL (interquartile interval: 24, 3,420). High baseline VL was associated with increased risk of both ischemic (HR: 1.3; 95% CI = 0.96-1.7) and hemorrhagic stroke (HR: 3.1; 95% CI = 1.6-5.9). In time-updated models, high VL was also associated with an increased risk of any stroke (HR: 1.8; 95% CI = 1.4-2.3). We observed no association between cumulative VL and stroke risk.ConclusionsOur findings are consistent with the hypothesis that elevated HIV VL may increase stroke risk, regardless of previous VL levels.

BackgroundMost 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.SettingCNICS, a U.S. multisite clinical cohort of PLWH in care.MethodsWe 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.ResultsAmong 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.ConclusionIschemic 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.

ObjectivesEvaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era.MethodsBetween 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time.ResultsMean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens.ConclusionsThere is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.

BackgroundType 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.MethodsPotential 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.ResultsWe 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).ConclusionsRates 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.

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

BackgroundAdvances 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.

ObjectiveAnaemia is common among people living with HIV (PLWH) and has been associated with certain, often older, antiretroviral medications. Information on current antiretroviral therapy (ART) and anaemia is limited. The objective was to compare the associations between anaemia incidence or haemoglobin change with core ART classes in the current ART era.DesignRetrospective cohort study.SettingUSA-based prospective clinical cohort of PLWH aged 18 and above receiving care at eight sites between January 2010 and March 2018.Participants16 505 PLWH were included in this study.Main outcome measuresAnaemia risk and haemoglobin change were estimated among PLWH for person-time on a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI)-based regimen, relative to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based reference. We also examined PLWH on regimens containing multiple core classes. Cox proportional hazards regression analyses were conducted to measure the associations between time-updated ART classes and incident anaemia or severe anaemia. Linear mixed effects models were used to examine the relationships between ART classes and haemoglobin change.ResultsDuring a median of 4.9 years of follow-up, 1040 developed anaemia and 488 developed severe anaemia. Compared with NNRTI use, INSTI-based regimens were associated with an increased risk of anaemia (adjusted HR (aHR) 1.26, 95% CI 1.00 to 1.58) and severe anaemia (aHR 1.51, 95% CI 1.07 to 2.11) and a decrease in haemoglobin level. Time on multiple core classes was also associated with increased anaemia risk (aHR 1.39, 95% CI 1.13 to 1.70), while no associations were found for PI use.ConclusionThese findings suggest INSTI use may increase the risk of anaemia. If confirmed, screening for anaemia development in users of INSTIs may be beneficial. Further research into the underlying mechanisms is warranted.

BackgroundSubstance use is common among people living with human immunodeficiency virus (PLWH) and a barrier to achieving viral suppression. Among PLWH who report illicit drug use, we evaluated associations between HIV viral load (VL) and reduced use of illicit opioids, methamphetamine/crystal, cocaine/crack, and marijuana, regardless of whether or not abstinence was achieved.MethodsThis was a longitudinal cohort study of PLWH from 7 HIV clinics or 4 clinical studies. We used joint longitudinal and survival models to examine the impact of decreasing drug use and of abstinence for each drug on viral suppression. We repeated analyses using linear mixed models to examine associations between change in frequency of drug use and VL.ResultsThe number of PLWH who were using each drug at baseline ranged from n = 568 (illicit opioids) to n = 4272 (marijuana). Abstinence was associated with higher odds of viral suppression (odds ratio [OR], 1.4-2.2) and lower relative VL (ranging from 21% to 42% by drug) for all 4 drug categories. Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with VL suppression (OR, 2.2, 1.6, respectively). Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with lower relative VL (47%, 38%, respectively).ConclusionsAbstinence was associated with viral suppression. In addition, reducing use of illicit opioids or methamphetamine/crystal, even without abstinence, was also associated with viral suppression. Our findings highlight the impact of reducing substance use, even when abstinence is not achieved, and the potential benefits of medications, behavioral interventions, and harm-reduction interventions.

BackgroundGuidelines for initial antiretroviral treatment (ART) regimens have evolved, with integrase strand transfer inhibitors (INSTIs) 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.SettingWe examined 2 groups of PLWH at 8 clinics who initiated ART regimens (August 1, 2013-March 31, 2017): those ART treatment-naive at initiation, and those treatment-experienced.MethodsThe 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.ResultsAmong 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 were similar across regimens for the combined outcome of regimen discontinuation or treatment switch. The hazard ratios for VF comparing dolutegravir- to darunavir-based regimens was 0.30 (95% CI: 0.2 to 0.6) among previously treatment-naive PLWH and was 0.60 (95% CI: 0.4 to 0.8) among treatment-experienced PLWH.ConclusionsThe proportion of previously treatment-naive 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-naive and treatment-experienced PLWH.

ObjectiveBilirubin 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).MethodsPotential 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

BackgroundPeople living with HIV are at risk of increased myocardial infarction (MI). Cumulative HIV viral load (VL) has been proposed as a better measure of HIV inflammation than other measures of VL, like baseline VL, but its associations with MI are not known.MethodsThe multisite Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort includes clinical data and centrally adjudicated MI with distinction between atheroembolic MI (type 1) and MI related to supply-demand mismatch (type 2). We examined CNICS participants who were not on antiretroviral therapy (ART) at enrollment. Cumulative VL (copy-days of virus) from 6 months after enrollment was estimated with a time-weighted sum using the trapezoidal rule. We modeled associations of cumulative and baseline VL with MI by type using marginal structural Cox models. We contrasted the 75% percentile of the VL distribution with the 25% percentile.ResultsAmong 11,324 participants, 218 MIs occurred between 1996 and 2016. Higher cumulative VL was associated with risk of all MI (hazard ratio [HR] = 1.72; 95% confidence interval [CI] = 1.26, 2.36), type 1 MI (HR = 1.23; 95% CI = 0.78, 1.96), and type 2 MI (HR = 2.52; 95% CI = 1.74, 3.66). While off ART, cumulative VL had a stronger association with type 1 MI (HR = 2.13; 95% CI = 1.15, 3.94) than type 2 MI (HR = 1.25; 95% CI = 0.70, 2.25). Baseline VL was associated with all MI (HR = 1.60; 95% CI = 1.28, 2.01), type 1 MI (HR = 1.73; 95% CI = 1.26, 2.38), and type 2 MI (HR = 1.51; 95% CI = 1.10, 2.08).ConclusionsHigher cumulative and baseline VL is associated with all MI, with a particularly strong association between cumulative VL and type 2 MI.

PurposeSubstance use is linked with poor outcomes among people living with HIV (PLWH) and is associated with mental health disorders. This analysis examines the impact of decreasing substance use, even without abstinence, on depressive symptoms among PLWH.MethodsData are from PLWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Sites cohort. Participants completed longitudinal assessments of substance use (modified ASSIST) and depressive symptoms (PHQ-9). Changes in substance use frequency were categorized as abstinence, reduced use, and nondecreasing use. Adjusted linear mixed models with time-updated change in substance use frequency and depressive symptom scores were used to examine associations between changes in the use of individual substances and depressive symptoms. Analyses were repeated using joint longitudinal survival models to examine associations with a high (PHQ-9 ≥10) score.ResultsAmong 9905 PLWH, 728 used cocaine/crack, 1016 used amphetamine-type substances (ATS), 290 used illicit opiates, and 3277 used marijuana at baseline. Changes in ATS use were associated with the greatest improvements in depressive symptoms: stopping ATS led to a mean decrease of PHQ-9 by 2.2 points (95% CI: 1.8 to 2.7) and a 61% lower odds of PHQ-9 score ≥10 (95% CI: 0.30 to 0.52), and decreasing ATS use led to a mean decrease of 1.7 points (95% CI: 1.2 to 2.3) and a 62% lower odds of PHQ-9 score ≥10 (95% CI: 0.25 to 0.56). Stopping and reducing marijuana and stopping cocaine/crack use were also associated with improvement in depressive symptoms.ConclusionsWe demonstrated that both substance use reduction and abstinence are associated with improvements in depressive symptoms over time.

BackgroundBecause HIV viral suppression is essential for optimal outcomes and prevention efforts, understanding trends and predictors is imperative to inform public health policy.ObjectiveTo evaluate viral suppression trends in people living with HIV (PLWH), including the relationship of associated factors, such as demographic characteristics and integrase strand transfer inhibitor (ISTI) use.DesignLongitudinal observational cohort study.Setting8 HIV clinics across the United States.ParticipantsPLWH receiving clinical care.MeasurementsTo understand trends in viral suppression (≤400 copies/mL), annual viral suppression rates from 1997 to 2015 were determined. Analyses were repeated with tests limited to 1 random test per person per year and using inverse probability of censoring weights to address loss to follow-up. Joint longitudinal and survival models and linear mixed models of PLWH receiving antiretroviral therapy (ART) were used to examine associations between viral suppression or continuous viral load (VL) levels and demographic factors, substance use, adherence, and ISTI use.ResultsViral suppression increased from 32% in 1997 to 86% in 2015 on the basis of all tests among 31 930 PLWH. In adjusted analyses, being older (odds ratio [OR], 0.76 per decade [95% CI, 0.74 to 0.78]) and using an ISTI-based regimen (OR, 0.54 [CI, 0.51 to 0.57]) were associated with lower odds of having a detectable VL, and black race was associated with higher odds (OR, 1.68 [CI, 1.57 to 1.80]) (P < 0.001 for each). Similar patterns were seen with continuous VL levels; when analyses were limited to 2010 to 2015; and with adjustment for adherence, substance use, or depression.LimitationResults are limited to PLWH receiving clinical care.ConclusionHIV viral suppression rates have improved dramatically across the United States, which is likely partially attributable to improved ART, including ISTI-based regimens. However, disparities among younger and black PLWH merit attention.Primary funding sourceNational Institutes of Health.

Background: The United States' (US) opioid overdose epidemic has evolved into a combined stimulant/opioid epidemic, a pattern driven in part by mitigating opioid overdose risk, variable substance availability, and personal preferences. This study aimed to investigate the association between self-reported substance preference (heroin or methamphetamine) and behavioral/health outcomes among individuals who used both heroin and methamphetamine in the rural US. Methods: The Rural Opioid Initiative is a consortium of 8 research cohorts from 10 states and 65 rural counties that recruited individuals reporting past 30-day injection of any substance or opioid substance use by any route from 1/2018 to 3/2020. Analyses were restricted to participants ⩾18 years, who self-reported either heroin or methamphetamine as their preferred substance and past 30-day use of both heroin and methamphetamine. We examined cross-sectional associations between preferred substance (heroin versus methamphetamine) and behavioral and health outcomes using random effects meta-analysis with adjusted regression models. Results: Among 1239 participants, 61% (n = 752) reported heroin as their preferred substance. Adjusting for age, sex, and race/ethnicity, methamphetamine preference was associated with lower prevalence ratios for current naloxone possession (adjusted prevalence ratio [aPR] = 0.68; 95% Confidence Interval [95% CI] = 0.59-0.78; P -value ⩽.001), of ever being told they had the hepatitis C virus (HCV; aPR = 0.72; 95% CI: 0.61-0.85; P -value ⩽.001) and a personal history of overdose (aPR = 0.81; 95% CI = 0.73-0.90; P -value ⩽.001). Conclusion: In our study analyzing associations between preferred substance and various behavioral and health outcomes amongst people who use both heroin and methamphetamine, a majority of participants preferred heroin. Methamphetamine preference was associated with lower prevalence of naloxone possession, ever being told they had HCV, and prior history of an overdose. This study underscores the need for targeted harm reduction services for people who prefer methamphetamine in rural areas. [ABSTRACT FROM AUTHOR]