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BackgroundThe 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.MethodsBecause 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

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.

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.

BackgroundRates of early syphilis in US women are steadily increasing, but predictors of infection in this group are not clearly defined.MethodsThis retrospective analysis focused on women enrolled in the US CFAR Network of Integrated Clinical Systems cohort between January 2005 and December 2016 with syphilis testing performed. The primary outcome of incident syphilis infection was defined serologically as a newly positive test with positive confirmatory testing after a negative test or a 2-dilution increase in rapid plasma regain titer. Infection rates were calculated for each woman-year in care with testing. Predictors of syphilis were sought among sociodemographics, clinical information, and self-reported behaviors. Multivariable logistic regression models were created; a subgroup analysis assessed predictors in women of reproductive age.ResultsThe annual rate of incident syphilis among 4416 women engaged in human immunodeficiency virus (HIV) care and tested during the 12-year study period was 760/100 000 person-years. Independent predictors of infection were injection drug use as a risk factor for HIV acquisition (aOR, 2.2; 95% CI, 1.3-3.9), hepatitis C infection (aOR, 1.9; 95% CI, 1.1-3.4), black race (aOR, 2.2; 95% CI, 1.3-3.7 compared with white race), and more recent entry to care (since 2005 compared with 1994-2004). Predictors were similar in women aged 18-49.ConclusionsSyphilis infection is common among US women in HIV care. Syphilis screening and prevention efforts should focus on women reporting drug use and with hepatitis C coinfection. Future studies should identify specific behaviors that mediate syphilis acquisition risk in women who use drugs.

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.

ObjectiveHistorically, a high burden of resistance to antiretroviral therapy (ART) in heavily treatment-experienced (HTE) persons with HIV (PWH) resulted in limited treatment options (LTOs). We evaluated the prevalence, risk factors, and virologic control of HTE PWH with LTO throughout the modern ART era.DesignWe examined all ART-experienced PWH in care between 2000 and 2017 in the Centers for AIDS Research Network of Integrated Clinical Systems cohort.MethodsWe computed the annual prevalence of HTE PWH with LTO defined as having two or less available classes with two or less active drugs per class based on genotypic data and cumulative antiretroviral resistance. We used multivariable Cox proportional hazards models to examine risk of LTO by 3-year study entry periods adjusting for demographic and clinical characteristics.ResultsAmong 27 133 ART-experienced PWH, 916 were classified as having LTO. The prevalence of PWH with LTO was 5.2-7.5% in 2000-2006, decreased to 1.8% in 2007, and remained less than 1% after 2012. Persons entering the study in 2009-2011 had an 80% lower risk of LTO compared with those entering in 2006-2008 (adjusted hazard ratio 0.20; 95% confidence interval: 0.09-0.42). We found a significant increase in undetectable HIV viral loads among PWH ever classified as having LTO from less than 30% in 2001 to more than 80% in 2011, comparable with persons who never had LTO.ConclusionResults of this large multicenter study show a dramatic decline in the prevalence of PWH with LTO to less than 1% with the availability of more potent drugs and a marked increase in virologic suppression in the current ART era.

ObjectiveWe 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 (ART) adherence.DesignLongitudinal study in a multi-site observational clinical cohort.MethodsThe Center for AIDS Research Network of Integrated Clinical Systems (CNICS) Patient-Reported Outcomes (PROs) survey measures internalized HIV stigma yearly using a 4-item assessment (response scale 1 = strongly disagree to 5 = strongly agree). We obtained PRO, lab, and appointment data from six CNICS 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.ResultsBetween February 2016 - November 2018, 6,859 patients underwent stigma assessment and were 81% cis-men, 38% Black, 16% Latinx, 32% heterosexual-identified, and 49% ≥50 years of age. Mean stigma level was 2.00 (SD 1.08). Stigma was significantly associated with subsequent viremia (aOR = 1.16, 95% CI: 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).ConclusionsInternalized 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.

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).

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) = 1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR = 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR = 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) = 1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR = 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR = 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.

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.

BackgroundTransgender women (TW) are disproportionately affected by both HIV and cardiovascular disease (CVD).ObjectivesWe 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.DesignWe conducted a cross-sectional analysis of patients engaged in HIV care between October 2014 and February 2018.SettingThe 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.Patients221 TW, 2983 CW, and 13467 CM.MeasurementsThe 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).ResultsUsing 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.LimitationsPCE and FRS have not been validated in TW with HIV. Few adjudicated CVD events in the data set precluded analyses based on clinical outcomes.ConclusionsAfter 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.

Low perceived social support (SS) negatively impacts health outcomes. We developed a measure of perceived SS for use in HIV care. We sought and categorized legacy items, selecting strongest items within categories. We elicited SS concepts from patients in English/Spanish, coded transcripts to match item pool content, and developed new items for salient unrepresented content. In focus groups, patients prioritized highly-matched items. We conducted cognitive interviews on high-priority items, and validity testing on final items against two legacy measures. From interviews (n = 32), we matched the following concepts: sense of belonging/inclusion; communication; emotional support; feeling accepted by others as a person; companionship; and practical support. We identified a new concept: support from friends/family in remaining healthy. Focus groups (n = 23) prioritized emotional support, communication, and support to remain healthy. Cognitive interviews (n = 30) found items were well-understood. The final 8-item measure performed well with 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); brief, clinically relevant, sufficiently unidimensional measures of SS for use in HIV care.

BackgroundSelf-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.MethodsSamples: 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).MeasuresIn 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.AnalysisWe 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.ResultsAmong the CJ sample, the coefficient for log-VL was - 0.31 (95% CI = - 0.43, - 0.18; P

BackgroundPersons 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.MethodsWe 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.ResultsAmong 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.ConclusionsMortality 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.

BackgroundThe relationship of internalized HIV stigma to key care cascade metrics in the United States is not well established using large-scale, geographically diverse data.SettingCenter for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort study.MethodsBeginning 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.ResultsOf 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).ConclusionsHigher 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.

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

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.

BackgroundPeople living with HIV (PLWH) commonly report marijuana use for chronic pain, although 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).MethodsParticipants completed self-report measures of chronic pain and marijuana use at an index visit and were followed up for 1 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.ResultsOf 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 (interquartile range 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.ConclusionsWe 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.

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.

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;

BackgroundThe 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.MethodsWe 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.ResultsAmong 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.ConclusionsRacial/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.

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.

The Universal Myocardial infarction (MI) definition divides MIs into different types. Type 1 MIs (T1MI) result spontaneously from atherosclerotic plaque instability. Type 2 MIs (T2MI) are due to secondary causes of myocardial oxygen demand/supply mismatch such as occurs with sepsis. T2MI are much more common among those with HIV than in the general population. T1MI and T2MI have different mechanisms, risk factors, and potential treatments suggesting that they should be distinguished to achieve a better scientific understanding of MIs in HIV. We sought to determine whether MI type could be accurately predicted by patient characteristics without adjudication in HIV-infected individuals. We developed a statistical model to predict T2MI versus T1MI using adjudicated events from six sites utilizing demographic characteristics, traditional cardiovascular, and HIV-related risk factors. Validation was assessed in a seventh site via mean calibration, and discrimination level was assessed by the area under the curve (AUC). Of 812 MIs, 388 were T2MI. HIV-related factors including hepatitis C infection were predictive of T2MI, whereas traditional cardiovascular risk factors including total cholesterol predicted T1MI. The score predicted 69 T2MI in the validation sample resulting in poor calibration, given that 90 T2MIs were observed. The development sample AUC was 0.75 versus 0.65 in the validation sample, suggesting relatively poor discrimination. The level of discrimination to predict MI type based on patient characteristics is insufficient for individual level prediction. Adjudication is required to distinguish MI types, which is necessary to advance understanding of this important outcome among HIV populations.

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.

BACKGROUND:Patient-provider sexual risk behavior discussions occur infrequently but may be facilitated by high-quality sexual risk screening tools. OBJECTIVE:To develop the Sexual Risk Behavior Inventory (SRBI), a brief computer-administered patient-reported measure. DESIGN:Qualitative item development/quantitative instrument validation. PARTICIPANTS:We developed SRBI items based on patient interviews (n = 128) at four geographically diverse US primary care clinics. Patients were diverse in gender identity, sex, sexual orientation, age, race/ethnicity, and HIV status. We compared sexual risk behavior identified by the SRBI and the Risk Assessment Battery (RAB) among patients (n = 422). APPROACH:We constructed an item pool based on validated measures of sexual risk, developed an in-depth interview guide based on pool content, and used interviews to elicit new sexual risk concepts. We coded concepts, matched them to item pool content, and developed new content where needed. A provider team evaluated item clinical relevance. We conducted cognitive interviews to assess item comprehensibility. We administered the SRBI and the RAB to patients. KEY RESULTS:Common, clinically relevant concepts in the SRBI included number of sex partners; partner HIV status; partner use of antiretroviral medication (ART)/pre-exposure prophylaxis (PrEP); and recent sex without barrier protection, direction of anal sex, and concern regarding HIV/STI exposure. While 90% reported inconsistent condom use on the RAB, same-day SRBI administration revealed that for over one third, all their partners were on ART/PrEP. CONCLUSION:The SRBI is a brief, skip-patterned, clinically relevant measure that ascertains sexual risk behavior across sex, sexual orientation, gender identity, partner HIV serostatus, and partner treatment status, furnishing providers with context to determine gradations of risk for HIV/STI.

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.

BackgroundChronic pain occurs in up to 85% of persons living with HIV and is commonly treated with long-term opioid therapy (LTOT). We investigated the impact of chronic pain and LTOT on HIV outcomes.MethodsThis was prospective cohort study conducted between July 2015 and July 2016 in 5 HIV primary care clinics. Chronic pain was defined as ≥moderate pain for ≥3 months on the Brief Chronic Pain Questionnaire. Chronic pain and LTOT were assessed at an index visit. Suboptimal retention, defined as at least one "no-show" to primary care, and virologic failure were measured over the subsequent year. Multivariable logistic regression models were built for each outcome adjusting for site.ResultsAmong 2334 participants, 25% had chronic pain, 27% had suboptimal retention, 12% had virologic failure, and 19% were prescribed LTOT. Among individuals not on LTOT, chronic pain was associated with increased odds of suboptimal retention [adjusted odds ratio (aOR) 1.46, 95% confidence interval (CI): 1.10 to 1.93, P = 0.009] and virologic failure (aOR 1.97, 95% CI: 1.39 to 2.80, P < 0.001). Among individuals with chronic pain, there was no association between LTOT and retention, but LTOT was associated with lower rates of virologic failure (aOR 0.56, 95% CI: 0.33 to 0.96, P = 0.03).ConclusionsChronic pain in participants not on LTOT was associated with virologic failure. This reinforces the need to identify effective chronic pain treatments for persons living with HIV and investigate their impact on HIV outcomes. The apparent protective association between LTOT and virologic failure in those with pain merits further exploration.

BackgroundMeta-analyses of general population studies report mean low-density lipoprotein cholesterol (LDL-C) reductions of 30% to

BackgroundThere is persistent confusion as to whether abacavir (ABC) increases the risk of myocardial infarction (MI), and whether such risk differs by type 1 (T1MI) or 2 (T2MI) MI in adults with HIV.MethodsIncident MIs in North American Cohort Collaboration on Research and Design participants were identified from 2001 to 2013. Discrete time marginal structural models addressed channeling biases and time-dependent confounding to estimate crude hazard ratio (HR) and adjusted hazard ratio (aHR) and 95% confidence intervals; analyses were performed for T1MI and T2MI separately. A sensitivity analysis evaluated whether Framingham risk score (FRS) modified the effect of ABC on MI occurrence.ResultsEight thousand two hundred sixty-five adults who initiated antiretroviral therapy contributed 29,077 person-years and 123 MI events (65 T1MI and 58 T2MI). Median follow-up time was 2.9 (interquartile range 1.4-5.1) years. ABC initiators were more likely to have a history of injection drug use, hepatitis C virus infection, hypertension, diabetes, impaired kidney function, hyperlipidemia, low (

BackgroundAge-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.MethodsThis 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.ResultsAmong 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% (Ptrend < .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.ConclusionsMultimorbidity 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.

BackgroundOur aim was to describe alcohol consumption trajectories in a cohort of people living with HIV and determine clinical and sociodemographic predictors of each trajectory.MethodsThis is a prospective cohort study of 7,906 patients in the 7 Centers for AIDS Research Network of Integrated Clinical Systems sites. Alcohol consumption was categorized as none, moderate, and alcohol misuse. Predictors included age, race/ethnicity, depressive or anxiety symptoms, illicit drug use (opioids, methamphetamines, cocaine/crack), marijuana use, hepatitis C virus (HCV) infection, HIV transmission risk factor, and HIV disease progression. We estimated sex-stratified alcohol consumption trajectories and their predictors.ResultsWe found 7 trajectories of alcohol consumption in men: stable nondrinking and increased drinking (71% and 29% of initial nondrinking); stable moderate, reduced drinking, and increased alcohol misuse (59%, 21%, and 21% of initial moderate alcohol use); and stable alcohol misuse and reduced alcohol misuse (75% and 25% of initial alcohol misuse). Categories were similar in women, except lack of an increase to alcohol misuse trajectory among women that begin with moderate use. Older men and women were more likely to have stable nondrinking, while younger men were more likely to increase to or remain in alcohol misuse. Minorities, people with depressive or anxiety symptoms, HCV-infected individuals, and people who injected drugs were more likely to reduce use. Illicit drug use was associated with a reduction in overall drinking, while marijuana use was associated with stable moderate drinking or misuse.ConclusionsLongitudinal trajectories of increasing alcohol use and stable misuse highlight the need to integrate routine screening and alcohol misuse interventions into HIV primary 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.

BackgroundCancer remains an important cause of morbidity and mortality in people with human immunodeficiency virus (PWHIV) on effective antiretroviral therapy (ART). Estimates of cancer-attributable mortality can inform public health efforts.MethodsWe evaluated 46956 PWHIV receiving ART in North American HIV cohorts (1995-2009). Using information on incident cancers and deaths, we calculated population-attributable fractions (PAFs), estimating the proportion of deaths due to cancer. Calculations were based on proportional hazards models adjusted for age, sex, race, HIV risk group, calendar year, cohort, CD4 count, and viral load.ResultsThere were 1997 incident cancers and 8956 deaths during 267145 person-years of follow-up, and 11.9% of decedents had a prior cancer. An estimated 9.8% of deaths were attributable to cancer (cancer-attributable mortality rate 327 per 100000 person-years). PAFs were 2.6% for AIDS-defining cancers (ADCs, including non-Hodgkin lymphoma, 2.0% of deaths) and 7.1% for non-AIDS-defining cancers (NADCs: lung cancer, 2.3%; liver cancer, 0.9%). PAFs for NADCs were higher in males and increased strongly with age, reaching 12.5% in PWHIV aged 55+ years. Mortality rates attributable to ADCs and NADCs were highest for PWHIV with CD4 counts

BackgroundPrevious studies of cardiovascular disease (CVD) among HIV-infected individuals have been limited by the inability to validate and differentiate atherosclerotic type 1 myocardial infarctions (T1MIs) from other events. We sought to define the incidence of T1MIs and risk attributable to traditional and HIV-specific factors among participants in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and compare adjusted incidence rates (IRs) to the general population Atherosclerosis Risk in Communities (ARIC) cohort.MethodsWe ascertained and adjudicated incident MIs among individuals enrolled in 7 NA-ACCORD cohorts between 1995 and 2014. We calculated IRs, adjusted incidence rate ratios (aIRRs), and 95% confidence intervals of risk factors for T1MI using Poisson regression. We compared aIRRs of T1MIs in NA-ACCORD with those from ARIC.ResultsAmong 29,169 HIV-infected individuals, the IR for T1MIs was 2.57 (2.30 to 2.86) per 1000 person-years, and the aIRR was significantly higher compared with participants in ARIC [1.30 (1.09 to 1.56)]. In multivariable analysis restricted to HIV-infected individuals and including traditional CVD risk factors, the rate of T1MI increased with decreasing CD4 count [≥500 cells/μL: ref; 350-499 cells/μL: aIRR = 1.32 (0.98 to 1.77); 200-349 cells/μL: aIRR = 1.37 (1.01 to 1.86); 100-199 cells/μL: aIRR = 1.60 (1.09 to 2.34);

Background.The long-term effectiveness of human immunodeficiency virus (HIV) treatments containing integrase inhibitors is unknown.Methods.We use observational data from the Centers for AIDS Research Network of Integrated Clinical Systems and the Centers for Disease Control and Prevention to estimate 4-year risk of AIDS and all-cause mortality among 415 patients starting a raltegravir regimen compared to 2646 starting an efavirenz regimen (both regimens include emtricitabine and tenofovir disoproxil fumarate). We account for confounding and selection bias as well as generalizability by standardization for measured variables, and present both observational intent-to-treat and per-protocol estimates.Results.At treatment initiation, 12% of patients were female, 36% black, 13% Hispanic; median age was 37 years, CD4 count 321 cells/µL, and viral load 4.5 log10 copies/mL. Two hundred thirty-five patients incurred an AIDS-defining illness or died, and 741 patients left follow-up. After accounting for measured differences, the 4-year risk was similar among those starting both regimens (ie, intent-to treat hazard ratio [HR], 0.96 [95% confidence interval {CI}, .63-1.45]; risk difference, -0.9 [95% CI, -4.5 to 2.7]), as well as among those remaining on regimens (ie, per-protocol HR, 0.95 [95% CI, .59-1.54]; risk difference, -0.5 [95% CI, -3.8 to 2.9]).Conclusions.Raltegravir and efavirenz-based initial antiretroviral therapy have similar 4-year clinical effects. Vigilance regarding longer-term comparative effectiveness of HIV regimens using observational data is needed because large-scale experimental data are not forthcoming.

ObjectiveThe aim of this study was to assess whether ever reporting depressive symptoms affects mortality in the modern HIV treatment era.DesignA cohort study of HIV-infected adults in routine clinical care at seven sites in the USA.MethodsWe 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.ResultsA 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).ConclusionIn 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.

ImportanceThe Second Universal Definition of Myocardial Infarction (MI) divides MIs into different types. Type 1 MIs result spontaneously from instability of atherosclerotic plaque, whereas type 2 MIs occur in the setting of a mismatch between oxygen demand and supply, as with severe hypotension. Type 2 MIs are uncommon in the general population, but their frequency in human immunodeficiency virus (HIV)-infected individuals is unknown.ObjectivesTo characterize MIs, including type; identify causes of type 2 MIs; and compare demographic and clinical characteristics among HIV-infected individuals with type 1 vs type 2 MIs.Design, setting, and participantsThis longitudinal study identified potential MIs among patients with HIV receiving clinical care at 6 US sites from January 1, 1996, to March 1, 2014, using diagnoses and cardiac biomarkers recorded in the centralized data repository. Sites assembled deidentified packets, including physician notes and electrocardiograms, procedures, and clinical laboratory tests. Two physician experts adjudicated each event, categorizing each definite or probable MI as type 1 or type 2 and identifying the causes of type 2 MI.Main outcomes and measuresThe number and proportion of type 1 vs type 2 MIs, demographic and clinical characteristics among those with type 1 vs type 2 MIs, and the causes of type 2 MIs.ResultsAmong 571 patients (median age, 49 years [interquartile range, 43-55 years]; 430 men and 141 women) with definite or probable MIs, 288 MIs (50.4%) were type 2 and 283 (49.6%) were type 1. In analyses of type 1 MIs, 79 patients who underwent cardiac interventions, such as coronary artery bypass graft surgery, were also included, totaling 362 patients. Sepsis or bacteremia (100 [34.7%]) and recent use of cocaine or other illicit drugs (39 [13.5%]) were the most common causes of type 2 MIs. A higher proportion of patients with type 2 MIs were younger than 40 years (47 of 288 [16.3%] vs 32 of 362 [8.8%]) and had lower current CD4 cell counts (median, 230 vs 383 cells/µL), lipid levels (mean [SD] total cholesterol level, 167 [63] vs 190 [54] mg/dL, and mean (SD) Framingham risk scores (8% [7%] vs 10% [8%]) than those with type 1 MIs or who underwent cardiac interventions.Conclusions and relevanceApproximately half of all MIs among HIV-infected individuals were type 2 MIs caused by heterogeneous clinical conditions, including sepsis or bacteremia and recent use of cocaine or other illicit drugs. Demographic characteristics and cardiovascular risk factors among those with type 1 and type 2 MIs differed, suggesting the need to specifically consider type among HIV-infected individuals to further understand MI outcomes and to guide prevention and treatment.

Studies of persons living with HIV (PLWH) have compared current non-drinkers to at-risk drinkers without differentiating whether current non-drinkers had a prior alcohol use disorder (AUD). The purpose of this study was to compare current non-drinkers with and without a prior AUD on demographic and clinical characteristics to understand the impact of combining them. We included data from six sites across the US from 1/2013 to 3/2015. Patients completed tablet-based clinical assessments at routine clinic appointments using the most recent assessment. Current non-drinkers were identified by AUDIT-C scores of 0. We identified a prior probable AUD by a prior AUD diagnosis in the electronic medical record (EMR) or a report of attendance at alcohol treatment in the clinical assessment. We used multivariate logistic regression to examine factors associated with prior AUD. Among 2235 PLWH who were current non-drinkers, 36% had a prior AUD with more patients with an AUD identified by the clinical assessment than the EMR. Higher proportions with a prior AUD were male, depressed, and reported current drug use compared to non-drinkers without a prior AUD. Former cocaine/crack (70% vs. 25%), methamphetamine/crystal (49% vs. 16%), and opioid/heroin use (35% vs. 7%) were more commonly reported by those with a prior AUD. In adjusted analyses, male sex, past methamphetamine/crystal use, past marijuana use, past opioid/heroin use, past and current cocaine/crack use, and cigarette use were associated with a prior AUD. In conclusion, this study found that among non-drinking PLWH in routine clinical care, 36% had a prior AUD. We found key differences between those with and without prior AUD in demographic and clinical characteristics, including drug use and depression. These results suggest that non-drinkers are heterogeneous and need further differentiation in studies and that prior alcohol misuse (including alcohol treatment) should be included in behavioural health assessments as part of clinical care.

BackgroundDepression affects 20-30% of HIV-infected patients and is associated with worse HIV outcomes. Although effective depression treatment is available, depression is largely untreated or undertreated in this population.MethodsWe quantified gaps in antidepressant treatment, treatment adjustments, and outcomes among US patients in routine HIV care in the nationally distributed CNICS observational clinical cohort. This cohort combines detailed clinical data with regular, self-reported depressive severity assessments (Patient Health Questionnaire-9, PHQ-9). We considered whether participants with likely depression received antidepressants, whether participants on antidepressants with persistently high depressive symptoms received timely dose adjustments, and whether participants achieved depression remission. We considered a cross-sectional analysis (6,219 participants in care in 2011-2012) and a prospective analysis (2,936 participants newly initiating CNICS care when PHQ-9 screening was active).ResultsThe cross-sectional sample was 87% male, 53% Caucasian, 25% African American, and 18% Hispanic; the prospective sample was similar. In both samples, 39-44% had likely depression, with 44-60% of those receiving antidepressants. Of participants receiving antidepressants, 20-26% experienced persistently high depressive symptoms; only a small minority of those received antidepressant dose adjustments. Overall, 35-40% of participants on antidepressants achieved full depression remission. Remission among participants with persistently high depressive symptoms was rare regardless of dose adjustments.ConclusionsIn this large, diverse cohort of US patients engaged in routine HIV care, we observed large gaps in antidepressant treatment, timely dose adjustment to address persistently high depressive symptoms, and antidepressant treatment outcomes. These results highlight the importance of more effective pharmacologic depression treatment models for HIV-infected patients.

BackgroundHuman immunodeficiency virus (HIV)-infected patients coinfected with hepatitis B (HBV) and C (HCV) viruses are at increased risk of end-stage liver disease (ESLD). Whether modern antiretroviral therapy has reduced ESLD risk is unknown.MethodsTwelve clinical cohorts in the United States and Canada participating in the North American AIDS Cohort Collaboration on Research and Design validated ESLD events from 1996 to 2010. ESLD incidence rates and rate ratios according to hepatitis status adjusted for age, sex, race, cohort, time-updated CD4 cell count and HIV RNA were estimated in calendar periods corresponding to major changes in antiretroviral therapy: early (1996-2000), middle (2001-2005), and modern (2006-2010) eras.ResultsAmong 34 119 HIV-infected adults followed for 129 818 person-years, 380 incident ESLD outcomes occurred. ESLD incidence (per 1000 person-years) was highest in triply infected (11.57) followed by HBV- (8.72) and HCV- (6.10) coinfected vs 1.27 in HIV-monoinfected patients. Adjusted incidence rate ratios (95% confidence intervals) comparing the modern to the early antiretroviral era were 0.95 (.61-1.47) for HCV, 0.95 (.40-2.26) for HBV, and 1.52 (.46-5.02) for triply infected patients. Use of antiretrovirals dually activity against HBV increased over time. However, in the modern era, 35% of HBV-coinfected patients were not receiving tenofovir. There was little use of HCV therapy.ConclusionsDespite increasing use of antiretrovirals, no clear reduction in ESLD risk was observed over 15 years. Treatment with direct-acting antivirals for HCV and wider use of tenofovir-based regimens for HBV should be prioritized for coinfected patients.

BackgroundThere are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in care in the United States and Canada.MethodsWe studied HIV-infected participants in 16 cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) during 2000-2010. After excluding 16 737 (21%) with any AIDS-defining clinical events documented before NA-ACCORD enrollment, we analyzed incident OIs among the remaining 63 541 persons, most of whom received antiretroviral therapy during the observation. We calculated incidence rates per 100 person-years of observation (hereafter, "person-years") with 95% confidence intervals (CIs) for the first occurrence of any OI and select individual OIs during 2000-2003, 2004-2007, and 2008-2010.ResultsA total of 63 541 persons contributed 261 573 person-years, of whom 5836 (9%) developed at least 1 OI. The incidence rate of any first OI decreased over the 3 observation periods, with 3.0 cases, 2.4 cases, and 1.5 cases per 100 person-years of observation during 2000-2003, 2004-2007, and 2008-2010, respectively (Ptrend

BackgroundHIV infection and biomarkers of inflammation [measured by interleukin-6 (IL-6)], monocyte activation [soluble CD14 (sCD14)], and coagulation (D-dimer) are associated with morbidity and mortality. We hypothesized that these immunologic processes mediate (explain) some of the excess risk of mortality among HIV infected (HIV+) versus uninfected people independently of comorbid diseases.MethodsAmong 2350 (1521 HIV+) participants from the Veterans Aging Cohort Study Biomarker Cohort (VACS BC), we investigated whether the association between HIV and mortality was altered by adjustment for IL-6, sCD14, and D-dimer, accounting for confounders. Participants were followed from date of blood draw for biomarker assays (baseline) until death or July 25, 2013. Analyses included ordered logistic regression and Cox Proportional Hazards regression.ResultsDuring 6.9 years (median), 414 deaths occurred. The proportional odds of being in a higher quartile of IL-6, sCD14, or D-dimer were 2-3 fold higher for viremic HIV+ versus uninfected people. Mortality rates were higher among HIV+ compared with uninfected people [incidence rate ratio (95% CI): 1.31 (1.06 to 1.62)]. Mortality risk increased with increasing quartiles of IL-6, sCD14, and D-dimer regardless of HIV status. Adjustment for IL-6, sCD14, and D-dimer partially attenuated mortality risk among HIV+ people with unsuppressed viremia (HIV-1 RNA ≥10,000 copies per milliliter) compared with uninfected people-hazard ratio (95% CI) decreased from 2.18 (1.60 to 2.99) to 2.00 (1.45 to 2.76).ConclusionsHIV infection is associated with elevated IL-6, sCD14, and D-dimer, which are in turn associated with mortality. Baseline measures of these biomarkers partially mediate excess mortality risk among HIV+ versus uninfected people.

BackgroundAlcohol has particularly harmful health effects in HIV-infected patients; therefore, HIV clinics are an important setting for integration of brief alcohol intervention and alcohol pharmacotherapy to improve patient outcomes. Current practices of alcohol screening, counseling, and prescription of pharmacotherapy by HIV providers are unknown.MethodsWe conducted a cross-sectional survey of HIV providers from 8 HIV clinical sites across the United States. Surveys queried knowledge and use of alcohol screening, brief advice, counseling and pharmacotherapy, confidence and willingness to prescribe pharmacotherapy and barriers to their use of alcohol pharmacotherapy. We used multivariable logistic regression to examine provider factors associated with confidence and willingness to prescribe pharmacotherapy.ResultsProviders (N=158) were predominantly female (58%) and Caucasian (73%); almost half were infectious disease physicians and 31% had been in practice 10-20 years. Most providers (95%) reported always or usually screening for alcohol use, although only 10% reported using a formal screening tool. Over two-thirds never or rarely treated alcohol-dependent patients with pharmacotherapy themselves. Most (71%) referred alcohol-dependent patients for treatment. Knowledge regarding alcohol pharmacotherapy was low. The major barrier to prescribing pharmacotherapy was insufficient training on use of pharmacotherapy. Provider confidence ratings were positively correlated with their practice patterns.ConclusionsHIV providers reported high rates of screening for alcohol use, though few used a formal screening tool. Most providers referred alcohol dependent patients to outside resources for treatment. Few reported prescribing alcohol pharmacotherapy. Increased training on alcohol pharmacotherapy may increase confidence in prescribing and use of these medications in HIV care settings.

ObjectiveTo describe disparities along the depression treatment cascade, from indication for antidepressant treatment to effective treatment, in HIV-infected individuals by gender and race/ethnicity.MethodsThe Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) cohort includes 31,000 HIV-infected adults in routine clinical care at 8 sites. Individuals were included in the analysis if they had a depressive symptoms measure within one month of establishing HIV care at a CNICS site. Depressive symptoms were measured using the validated Patient Health Questionnaire-9 (PHQ-9). Indication for antidepressant treatment was defined as PHQ-9 ≥ 10 or a current antidepressant prescription. Antidepressant treatment was defined as a current antidepressant prescription. Evidence-based antidepressant treatment was considered treatment changes based on a person's most recent PHQ-9, in accordance with clinical guidelines. We calculated the cumulative probability of moving through the depression treatment cascade within 24 months of entering CNICS HIV care. We used multivariable Cox proportional hazards models to estimate associations between gender, race/ethnicity, and a range of depression outcomes.ResultsIn our cohort of HIV-infected adults in routine care, 47% had an indication for antidepressant treatment. Significant drop-offs along the depression treatment cascade were seen for the entire study sample. However, important disparities existed. Women were more likely to have an indication for antidepressant treatment (HR 1.54; 95% CI 1.34, 1.78), receive antidepressant treatment (HR 2.03; 95% CI 1.53, 2.69) and receive evidence-based antidepressant treatment (HR 1.67; 95% CI 1.03, 2.74), even after accounting for race/ethnicity. Black non-Hispanics (HR 0.47, 95% CI 0.35, 0.65), Hispanics (HR 0.63, 95% CI 0.44, 0.89) and other race/ethnicities (HR 0.35, 95% CI 0.17, 0.73) were less likely to initiate antidepressant treatment, compared to white non-Hispanics.ConclusionsIn our cohort of HIV-infected adults depressive symptoms were common. Important disparities in the prevalence of depressive symptoms and receipt of antidepressant treatment existed by gender and race/ethnicity.