Venous Thromboembolism Among People With HIV: Design, Implementation, and Findings of a Centralized Adjudication System in Clinical Care Sites Across the United States.

BACKGROUND: People with HIV (PWH) are at increased risk for venous thromboembolism (VTE). We conducted this study to characterize VTE including provoking factors among PWH in the current treatment era. METHODS: We included PWH with VTE between 2010 and 2020 at 6 sites in the CFAR Network of Integrated Clinical Systems cohort. We ascertained for possible VTE using diagnosis, VTE-related imaging, and VTE-related procedure codes, followed by centralized adjudication of primary data by expert physician reviewers. We evaluated sensitivity and positive predictive value of VTE ascertainment approaches. VTEs were classified by type and anatomic location. Reviewers identified provoking factors such as hospitalizations, infections, and other potential predisposing factors such as smoking. RESULTS: We identified 557 PWH with adjudicated VTE: 239 (43%) had pulmonary embolism with or without deep venous thrombosis, and 318 (57%) had deep venous thrombosis alone. Ascertainment with clinical diagnoses alone missed 6% of VTEs identified with multiple ascertainment approaches. DVTs not associated with intravenous lines were most often in the proximal lower extremities. Among PWH with VTE, common provoking factors included recent hospitalization (n = 134, 42%), infection (n = 133, 42%), and immobilization/bed rest (n = 78, 25%). Only 57 (10%) PWH had no provoking factor identified. Smoking (46%), HIV viremia (27%), and injection drug use (22%) were also common. CONCLUSIONS: We conducted a robust adjudication process that demonstrated the benefits of multiple ascertainment approaches followed by adjudication. Provoked VTEs were more common than unprovoked events. Nontraditional and modifiable potential predisposing factors such as viremia and smoking were common.

Hepatitis C Virus Micro-elimination Among People With HIV in San Diego: Are We on Track?

Background: Rising incidence of hepatitis C virus (HCV) among people with HIV (PWH) in San Diego County (SDC) was reported. In 2018, the University of California San Diego (UCSD) launched a micro-elimination initiative among PWH, and in 2020 SDC launched an initiative to reduce HCV incidence by 80% across 2015-2030. We model the impact of observed treatment scale-up on HCV micro-elimination among PWH in SDC. Methods: A model of HCV transmission among people who inject drugs (PWID) and men who have sex with men (MSM) was calibrated to SDC. The model was additionally stratified by age, gender, and HIV status. The model was calibrated to HCV viremia prevalence among PWH in 2010, 2018, and 2021 (42.1%, 18.5%, and 8.5%, respectively), and HCV seroprevalence among PWID aged 18-39 years, MSM, and MSM with HIV in 2015. We simulate treatment among PWH, weighted by UCSD Owen Clinic (reaching 26% of HCV-infected PWH) and non-UCSD treatment, calibrated to achieve the observed HCV viremia prevalence. We simulated HCV incidence with observed and further treatment scale-up (+/- risk reductions) among PWH. Results: Observed treatment scale-up from 2018 to 2021 will reduce HCV incidence among PWH in SDC from a mean of 429 infections/year in 2015 to 159 infections/year in 2030. County-wide scale-up to the maximum treatment rate achieved at UCSD Owen Clinic (in 2021) will reduce incidence by 69%, missing the 80% incidence reduction target by 2030 unless accompanied by behavioral risk reductions. Conclusions: As SDC progresses toward HCV micro-elimination among PWH, a comprehensive treatment and risk reduction approach is necessary to reach 2030 targets.

Associations between alcohol and cigarette use and type 1 and 2 myocardial infarction among people with HIV.

OBJECTIVES: People with HIV have a higher risk of myocardial infarction (MI) than the general population, with a greater proportion of type 2 MI (T2MI) due to oxygen demand-supply mismatch compared with type 1 (T1MI) resulting from atherothrombotic plaque disruption. People living with HIV report a greater prevalence of cigarette and alcohol use than do the general population. Alcohol use and smoking as risk factors for MI by type are not well studied among people living with HIV. We examined longitudinal associations between smoking and alcohol use patterns and MI by type among people living with HIV. DESIGN AND METHODS: Using longitudinal data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort, we conducted time-updated Cox proportional hazards models to determine the impact of smoking and alcohol consumption on adjudicated T1MI and T2MI. RESULTS: Among 13 506 people living with HIV, with a median 4 years of follow-up, we observed 177 T1MI and 141 T2MI. Current smoking was associated with a 60% increase in risk of both T1MI and T2MI. In addition, every cigarette smoked per day was associated with a 4% increase in risk of T1MI, with a suggestive, but not significant, 2% increase for T2MI. Cigarette use had a greater impact on T1MI for men than for women and on T2MI for women than for men. Increasing alcohol use was associated with a lower risk of T1MI but not T2MI. Frequency of heavy episodic alcohol use was not associated with MI. CONCLUSIONS: Our findings reinforce the prioritization of smoking reduction, even without cessation, and cessation among people living with HIV for MI prevention and highlight the different impacts on MI type by gender.

Development of Frail RISC-HIV: a Risk Score for Predicting Frailty Risk in the Short-term for Care of People with HIV.

OBJECTIVE: Frailty is common among people with HIV (PWH), so we developed frail risk in the short-term for care (RISC)-HIV, a frailty prediction risk score for HIV clinical decision-making. DESIGN: We followed PWH for up to 2 years to identify short-term predictors of becoming frail. METHODS: We predicted frailty risk among PWH at seven HIV clinics across the United States. A modified self-reported Fried Phenotype captured frailty, including fatigue, weight loss, inactivity, and poor mobility. PWH without frailty were separated into training and validation sets and followed until becoming frail or 2 years. Bayesian Model Averaging (BMA) and five-fold-cross-validation Lasso regression selected predictors of frailty. Predictors were selected by BMA if they had a greater than 45% probability of being in the best model and by Lasso if they minimized mean squared error. We included age, sex, and variables selected by both BMA and Lasso in Frail RISC-HIV by associating incident frailty with each selected variable in Cox models. Frail RISC-HIV performance was assessed in the validation set by Harrell's C and lift plots. RESULTS: Among 3170 PWH (training set), 7% developed frailty, whereas among 1510 PWH (validation set), 12% developed frailty. BMA and Lasso selected baseline frailty score, prescribed antidepressants, prescribed antiretroviral therapy, depressive symptomology, and current marijuana and illicit opioid use. Discrimination was acceptable in the validation set, with Harrell's C of 0.76 (95% confidence interval: 0.73-0.79) and sensitivity of 80% and specificity of 61% at a 5% frailty risk cutoff. CONCLUSIONS: Frail RISC-HIV is a simple, easily implemented tool to assist in classifying PWH at risk for frailty in clinics.

Chronic obstructive pulmonary disease and the risk for myocardial infarction by type in people with HIV.

OBJECTIVES: The relationship between chronic obstructive pulmonary disease (COPD) and cardiovascular disease in people with HIV (PWH) is incompletely understood. We determined whether COPD is associated with risk of myocardial infarction (MI) among PWH, and if this differs for type 1 (T1MI) and type 2 (T2MI). DESIGN: We utilized data from five sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, a multisite observational study. METHODS: Our primary outcome was an adjudicated MI, classified as T1MI or T2MI. We defined COPD based on a validated algorithm requiring COPD diagnosis codes and at least 90-day continuous supply of inhalers. We conducted time-to-event analyses to first MI and used multivariable Cox proportional hazards models to measure associations between COPD and MI. RESULTS: Among 12 046 PWH, 945 had COPD. Overall, 309 PWH had an MI: 58% had T1MI ( N  = 178) and 42% T2MI ( N  = 131). In adjusted models, COPD was associated with a significantly increased risk of all MI [adjusted hazard ratio (aHR) 2.68 (95% confidence interval (CI) 1.99-3.60)] even after including self-reported smoking [aHR 2.40 (95% CI 1.76-3.26)]. COPD was also associated with significantly increased risk of T1MI and T2MI individually, and with sepsis and non-sepsis causes of T2MI. Associations were generally minimally changed adjusting for substance use. CONCLUSION: COPD is associated with a substantially increased risk for MI, including both T1MI and T2MI, among PWH. Given the association with both T1MI and T2MI, diverse mechanistic pathways are involved. Future strategies to decrease risk of T1MI and T2MI in PWH who have COPD are needed.

Racial and ethnic disparities in coronavirus disease 2019 disease incidence independent of comorbidities, among people with HIV in the United States.

OBJECTIVES: To 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. DESIGN: Observational study within the CFAR Network of Integrated Clinical Systems cohort in seven cities during 2020. METHODS: We 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. RESULTS: Among 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. CONCLUSION: Our 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.

People with HIV have a higher risk of COVID-19 diagnosis but similar outcomes to the general population.

BACKGROUND: We investigated the effect of HIV on COVID-19 outcomes with attention to selection bias due to differential testing and comorbidity burden. METHODS: This was a retrospective cohort analysis using four hierarchical outcomes: positive SARS-CoV-2 test, COVID-19 hospitalization, intensive care unit (ICU) admission and hospital mortality. The effect of HIV status was assessed using traditional covariate-adjusted, inverse probability-weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV-IPWs) and combined models. Among people living with HIV (PWH), we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did and those who did not develop study outcomes using receiver operating characteristic analysis. RESULTS: Between March and November 2020, 63 319 people were receiving primary care services at the University of California San Diego (UCSD), of whom 4017 were PWH. The PWH had 2.1 times the odds of a positive SARS-CoV-2 test compared with those without HIV after weighting for potential testing bias, comorbidity burden and HIV-IPW [95% confidence interval (CI): 1.6-2.8]. Relative to people without HIV, PWH did not have an increased rate of COVID-19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR) = 0.5, 95% CI: 0.1-1.4]. PWH did not have a different rate of ICU admission (aIRR = 1.08, 95% CI: 0.31-3.80) or of in-hospital death (aIRR = 0.92, 95% CI: 0.08-10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH. CONCLUSIONS: People living with HIV have a higher risk of COVID-19 diagnosis than those without HIV but the outcomes are similar in both groups.

Tobacco smoking and binge alcohol use are associated with incident venous thromboembolism in an HIV cohort.

BACKGROUND: People 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. METHODS: We 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. RESULTS: During 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. CONCLUSIONS: Current 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.

Brief Report: Insomnia and Risk of Myocardial Infarction Among People With HIV.

BACKGROUND: Insomnia 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. SETTING: Longitudinal cohort study of PWH at 5 Centers for AIDS Research Network of Integrated Clinical Systems sites. METHODS: Clinical 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). RESULTS: Among 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). CONCLUSIONS: PWH 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.

Anal cancer incidence in men with HIV who have sex with men: are black men at higher risk?

OBJECTIVE: To assess differences in anal cancer incidence between racial/ethnic groups among a clinical cohort of men with HIV who have sex with men. DESIGN: Clinical cohort study. METHODS: We studied men who have sex with men (MSM) in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who initiated antiretroviral therapy (ART) under HIV care in CNICS. We compared anal cancer incidence between Black and non-Black men and calculated hazard ratios controlling for demographic characteristics (age, CNICS site, year of ART initiation), HIV disease indicators (nadir CD4+, peak HIV RNA), and co-infection/behavioral factors including hepatitis B virus (HBV), hepatitis C virus (HCV), tobacco smoking and alcohol abuse. RESULTS: We studied 7473 MSM with HIV who contributed 41 810 person-years of follow-up after initiating ART between 1996 and 2014 in CNICS. Forty-one individuals had an incident diagnosis of anal cancer under observation. Crude rates of anal cancer were 204 versus 61 per 100 000 person-years among Black versus non-Black MSM. The weighted hazard ratio for anal cancer in Black MSM (adjusting for demographics, HIV disease factors, and co-infection/behavioral factors) was 2.37 (95% confidence interval: 1.17, 4.82) compared to non-Black MSM. CONCLUSIONS: In this large multicenter cohort, Black MSM were at significantly increased risk for anal cancer compared to non-Black MSM. Further detailed studies evaluating factors impacting anal cancer incidence and outcomes in Black men with HIV are necessary. Inclusion of more diverse study cohorts may elucidate modifiable factors associated with increased anal cancer risk experienced by Black MSM.

Effective Human Immunodeficiency Virus Molecular Surveillance Requires Identification of Incident Cases of Infection.

BACKGROUND: Ending the human immunodeficiency virus (HIV) epidemic requires knowledge of key drivers of spread of HIV infection. METHODS: Between 1996 and 2018, 1119 newly and previously diagnosed, therapy-naive persons with HIV (PWH) from San Diego were followed. A genetic distance-based network was inferred using pol sequences, and genetic clusters grew over time through linkage of sequences from newly observed infections. Cox proportional hazards models were used to identify factors associated with the rate of growth. These results were used to predict the impact of a hypothetical intervention targeting PWH with incident infection. Comparison was made to the Centers for Disease Control and Prevention (CDC) Ending the HIV Epidemic (EHE) molecular surveillance strategy, which prioritizes clusters recently linked to all new HIV diagnoses and does not incorporate data on incident infections. RESULTS: Overall, 219 genetic linkages to incident infections were identified over a median follow-up of 8.8 years. Incident cluster growth was strongly associated with proportion of PWH in the cluster who themselves had incident infection (hazard ratio, 44.09 [95% confidence interval, 17.09-113.78]). The CDC EHE molecular surveillance strategy identified 11 linkages to incident infections a genetic distance threshold of 0.5%, and 24 linkages at 1.5%. CONCLUSIONS: Over the past 2 decades, incident infections drove incident HIV cluster growth in San Diego. The current CDC EHE molecular detection and response strategy would not have identified most transmission events arising from those with incident infection in San Diego. Molecular surveillance that includes detection of incident cases will provide a more effective strategy for EHE.

Longitudinal Associations of Syndemic Conditions with Antiretroviral Therapy Adherence and HIV Viral Suppression Among HIV-Infected Patients in Primary Care.

Psychosocial syndemic conditions have received more attention regarding their deleterious effects on HIV acquisition risk than for their potential impact on HIV treatment and viral suppression. To examine syndemic conditions' impact on the HIV care continuum, we analyzed data collected from people living with HIV (N = 14,261) receiving care through The Centers for AIDS Research Network of Integrated Clinical Systems at seven sites from 2007 to 2017 who provided patient-reported outcomes ∼4-6 months apart. Syndemic condition count (depression, anxiety, substance use, and hazardous drinking), sexual risk group, and time in care were modeled to predict antiretroviral therapy (ART) adherence and viral suppression (HIV RNA <400 copies/mL) using multilevel logistic regression. Comparing patients with each other, odds of ART adherence were 61.6% lower per between-patient syndemic condition [adjusted odds ratio (AOR) = 0.384; 95% confidence interval (CI), 0.362-0.408]; comparing patients with themselves, odds of ART adherence were 36.4% lower per within-patient syndemic condition (AOR = 0.636 95% CI, 0.606-0.667). Odds of viral suppression were 29.3% lower per between-patient syndemic condition (AOR = 0.707; 95% CI, 0.644-0.778) and 27.7% lower per within-patient syndemic condition (AOR = 0.723; 95% CI, 0.671-0.780). Controlling for the effects of adherence (AOR = 5.522; 95% CI, 4.67-6.53), each additional clinic visit was associated with 1.296 times higher odds of viral suppression (AOR = 1.296; 95% CI, 1.22-1.38), but syndemic conditions were not significant. Deploying effective interventions within clinics to identify and treat syndemic conditions and bolster ART adherence and continued engagement in care can help control the HIV epidemic, even within academic medical settings in the era of increasingly potent ART.

Estimating HIV transmissions in a large U.S. clinic-based sample: effects of time and syndemic conditions.

INTRODUCTION: Little 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. METHODS: Data 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 (mean = 4.3 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 RNA < 400/mL) using hierarchical linear modelling. RESULTS: Patients 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; p < 0.0005). Cisgender women, cisgender heterosexual men and cisgender men of undisclosed sexual orientation had, respectively, 0.47 (95% CI: 0.35 to 0.59; p < 0.0005), 0.34 (95% CI: 0.20 to 0.49; p < 0.0005) and 0.22 (95% CI: 0.09 to 0.35; p < 0.005) 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; p < 0.0005). Each between-syndemic condition predicted 0.23 estimated HIV transmissions/100 patients/year (95% CI: 0.17 to 0.28; p < 0.0005). CONCLUSIONS: Estimated 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.

Types of Stroke Among People Living With HIV in the United States.

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.

Hepatitis C Knowledge and Recent Diagnosis Affect Hepatitis C Treatment Willingness in Persons Living With HIV.

BACKGROUND: We assessed the impact of health literacy and hepatitis C (HCV) knowledge on HCV treatment willingness among people living with HIV (PLWH) at an academic HIV clinic. METHODS: Cross-sectional analysis of PLWH coinfected with HCV who completed health literacy, HIV literacy, and HCV knowledge inventories. We estimated the prevalence of low health literacy, HIV knowledge, and HCV knowledge sampled from 3-comparison groups: PLWH not referred for HCV, referred but who "not showed" to the HCV clinic, and referred and attended the HCV clinic. We used mixed-model linear and logistic regression to ascertain predictors of low health literacy, HIV knowledge, HCV knowledge, and predictors of willingness to start HCV treatment. RESULTS: We enrolled 151 PLWH; 17% were female, 38% non-White, and 60% without a high-school education. Approximately, 68% were men who have sex with men, of whom 62% used intravenous drugs. The prevalence of low health, HIV knowledge, and HCV knowledge was 10%, 32%, and 29%, respectively. Predictors of low health literacy were being Hispanic, cirrhotic, and not completing high-school education. Low HCV knowledge was observed in female, non-White, and those diagnosed with HCV for a decade. In adjusted analyses, PLWH living with HCV for a decade (OR: 0.23) were less likely to be very willing to be treated for HCV. By contrast, those with high HCV knowledge were more likely to be very willing to receive treatment (OR: 1.27). CONCLUSION: Low HCV knowledge and living with HCV for at least a decade are under-recognized negative predictors for PLWH's willingness to receive HCV treatment. CLINICAL TRIALS REGISTRATION: ClinicaTrials.gov identifier: NCT20170991.

Brief Report: Weight Gain Following ART Initiation in ART-Naïve People Living With HIV in the Current Treatment Era.

OBJECTIVES: Evaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era. METHODS: Between 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. RESULTS: Mean 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. CONCLUSIONS: There 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.

Internalized HIV stigma predicts subsequent viremia in US HIV patients through depressive symptoms and antiretroviral therapy adherence.

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 ß = 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.

The role of barriers to care on the propensity for hepatitis C virus nonreferral among people living with HIV.

: Twenty-five percent of HIV/hepatitis C virus (HCV) coinfected patients were not referred for HCV treatment despite unrestricted access in California to direct-acting antivirals (DAA) in 2018. Having unstable housing and ongoing drug use directly affected HCV treatment nonreferral. However, psychiatric history and alcohol use impacted HCV treatment nonreferral through the mediation of not being engaged in HIV care. Achieving HCV elimination requires DAA treatment outside conventional health settings, including substance rehabilitation centers, mental health crisis houses, and homeless shelters.

Cardiovascular disease risk among transgender women living with HIV in the United States.

BACKGROUND: Transgender women (TW) are disproportionately affected by both HIV and cardiovascular disease (CVD). OBJECTIVES: We aim to quantify prevalence of elevated predicted CVD risk for TW compared to cisgender women (CW) and cisgender men (CM) in HIV care and describe the impact of multiple operationalizations of CVD risk score calculations for TW. DESIGN: We conducted a cross-sectional analysis of patients engaged in HIV care between October 2014 and February 2018. SETTING: The Centers for AIDS Research Network of Integrated Clinical Systems, a collaboration of 8 HIV clinical sites in the United States contributed data for this analysis. PATIENTS: 221 TW, 2983 CW, and 13467 CM. MEASUREMENTS: The measure of interest is prevalence of elevated 10-year cardiovascular disease risk based on ACC/AHA Pooled Cohort Risk Assessment equations (PCE) and the Framingham Risk Score (FRS), calculated for TW by: birth-assigned sex (male); history of exogenous sex hormone use (female/male); and current gender (female). RESULTS: Using birth-assigned sex, the adjusted prevalence ratio (aPR) was 2.52 (95% CI: 1.08,5.86) and 2.58 (95% CI: 1.71,3.89) comparing TW to CW, by PCE and FRS, respectively. It was 1.25 (95% CI: 0.54,2.87) and 1.25 (95% CI: 0.84,1.86) comparing TW to CM, by PCE and FRS, respectively. If TW were classified according to current gender versus birth-assigned sex, their predicted CVD risk scores were lower. LIMITATIONS: PCE and FRS have not been validated in TW with HIV. Few adjudicated CVD events in the data set precluded analyses based on clinical outcomes. CONCLUSIONS: After adjustment for demographics and history of HIV care, prevalence of elevated CVD risk in TW was similar to CM and equal to or higher than in CW, depending operationalization of the sex variable. Future studies with CVD outcomes are needed to help clinicians accurately estimate CVD risk among TW with HIV.

Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

INTRODUCTION: Weight 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-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). METHODS: Adult, treatment-naïve 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 >10% weight gain at two and five years. RESULTS: Among 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 >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI). CONCLUSIONS: PWH 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.