Search

Funder: National Institutes of Health; Id: http://dx.doi.org/10.13039/100000002, 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.

OBJECTIVE Hepatitis C Virus (HCV) co-infection is associated with increased morbidity and mortality in people with HIV (PWH). Sustained virological response (SVR) decreases the risk of HCV-associated morbidity. We compared mortality, risk of AIDS-defining events, and non-AIDS non-liver (NANL) cancers between HCV co-infected PWH who reached SVR and mono-infected PWH. DESIGN Adult PWH from 21 cohorts in Europe and North America that collected HCV treatment data were eligible if they were HCV-free at time of ART initiation. METHODS Up to 10 mono-infected PWH were matched (on age, sex, date of ART start, HIV acquisition route, and being followed at the time of SVR) to each HCV co-infected PWH who reached SVR. Cox models were used to estimate relative hazards (HR) of all-cause mortality, AIDS-defining events, and NANL cancers after adjustment. RESULTS Among 62,495 PWH, 2,756 acquired HCV, of whom 649 reached SVR. For 582 of these, ≥1 mono-infected PWH could be matched, producing a total of 5,062 mono-infected PWH. The estimated HRs comparing HCV co-infected PWH who reached SVR with mono-infected PWH were 0.29 [95%CI 0.12-0.73] for mortality, 0.85 [0.42-1.74] for AIDS-defining events, and 1.21 [0.86-1.72] for NANL cancer. CONCLUSION PWH who reached SVR a short time after HCV acquisition were not at higher risk of overall mortality compared to mono-infected PWH. However, the apparent higher risk of NANL cancers in HCV co-infected PWH who reached SVR after a DAA-based treatment compared to mono-infected PWH, though compatible with a null association, suggests a need for monitoring of those events following SVR.

BACKGROUND Randomized trials (RCTs) from low- and middle-income settings suggested early initiation of antiretroviral therapy (ART) leads to higher mortality among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about impact of ART timing on mortality in similar people in high-income settings. METHODS Data on ART-naïve PWH diagnosed with CM from 1994-2012 from Europe/North America were pooled from the COHERE, NA-ACCORD and CNICS HIV cohort collaborations. Follow-up was considered from the date of CM diagnosis to earliest of the following: death, last follow-up or 6 months. We used marginal structural models to mimic an RCT comparing effects of early (within 14 days of CM) with late (14-56 days after CM) ART on all-cause mortality, adjusting for potential confounders. RESULTS Of 190 participants identified, 33 (17%) died within 6 months. At CM diagnosis, median age was 38 years (interquartile range 33-44); CD4 count was 19 cells/mm3 (10-56); and HIV viral load was 5.3 log10 copies/mL (4.9-5.6). Most participants (157, 83%) were males and 145 (76%) started ART. Mimicking an RCT, with 190 people in each group, there were 13 deaths among participants following early ART regimen and 20 deaths among those following late ART regimen. Crude and adjusted hazard ratios comparing late with early ART were 1.28 (95% CI: 0.64, 2.56) and 1.40 (0.66, 2.95). CONCLUSIONS We found little evidence that early ART was associated with higher mortality among PWH presenting with CM in high income settings, although confidence intervals were wide.

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

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

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

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.Longitudinal cohort study of PWH at 5 Centers for AIDS Research Network of Integrated Clinical Systems sites.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).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).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.

Background To assess the possible impact of antiretroviral therapy improvements, aging, and comorbidities, we examined trends in all-cause and cause-specific hospitalization rates among persons with HIV (PWH) from 2005 to 2015. Methods In 6 clinical cohorts, we followed PWH in care (≥1 outpatient CD4 count or HIV load [VL] every 12 months) and categorized ICD codes of primary discharge diagnoses using modified Clinical Classifications Software. Poisson regression estimated hospitalization rate ratios for calendar time trends, adjusted for demographics, HIV risk factor, and annually updated age, CD4, and VL. Results Among 28 057 patients (125 724 person-years), from 2005 to 2015, the median CD4 increased from 389 to 580 cells/µL and virologic suppression from 55% to 85% of patients. Unadjusted all-cause hospitalization rates decreased from 22.3 per 100 person-years in 2005 (95% confidence interval [CI], 20.6–24.1) to 13.0 in 2015 (95% CI, 12.2–14.0). Unadjusted rates decreased for almost all diagnostic categories. Adjusted rates decreased for all-cause, cardiovascular, and AIDS-defining conditions, increased for non-AIDS–defining infection, and were stable for most other categories. Conclusions Among PWH with increasing CD4 counts and viral suppression, unadjusted hospitalization rates decreased for all-cause and most cause-specific hospitalizations, despite the potential effects of aging, comorbidities, and cumulative exposure to HIV and antiretrovirals.

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

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

IntroductionLittle is known about onward HIV transmissions from people living with HIV (PLWH) in care. Antiretroviral therapy (ART) has increased in potency, and treatment as prevention (TasP) is an important component of ending the epidemic. Syndemic theory has informed modelling of HIV risk but has yet to inform modelling of HIV transmissions.MethodsData were from 61,198 primary HIV care visits for 14,261 PLWH receiving care through the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) at seven United States (U.S.) sites from 2007 to 2017. Patient-reported outcomes and measures (PROs) of syndemic conditions - depressive symptoms, anxiety symptoms, drug use (opiates, amphetamines, crack/cocaine) and alcohol use - were collected approximately four to six months apart along with sexual behaviours (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&nbsp

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.

Supplemental Material, sj-pdf-1-std-10.1177_09564624211032796 for Feasibility of implementing a same-day electronic screening tool for clinical assessment to measure patient-reported outcomes for eliciting actionable information on adherence to HIV medication and related factors in a busy Canadian urban HIV clinic by Shivali Suri, Deborah Yoong, Duncan Short, Darrell HS Tan, Mark Naccarato, Heidi M Crane, Alexandra Musten, Rob J Fredericksen, William B Lober and Kevin Gough in International Journal of STD & AIDS

Additional file 1: Figure 1. Causes of Missing Data Across Three STTR Studies.

Historically, 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.We examined all ART-experienced PWH in care between 2000 and 2017 in the Centers for AIDS Research Network of Integrated Clinical Systems cohort.We 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.Among 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.Results 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.

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.

Evidence suggests priorities differ between patients in HIV care and their providers regarding topics most important to address in care. At five U.S. sites, we asked patients and providers to prioritize 25 potential topic areas to address during routine visits, and invited patients to discuss selection rationale. Patients (n=206) and providers (n=17) showed high discordance in rank order priorities (Γ(2) (24, 223)=71.12; p

Additional file 1: Table S1. A summary of genotyping and imputation platforms utilized to generate the final study data set. Table S2. Description of previously published genome-wide association studies (GWAS) in European populations that were used in polygenic risk score analyses. Table S3. Number of variants used to derive various polygenic risk scores for different traits and diseases. Table S9. Number of expression quantitative trait loci controlled by HIV-specific loci in CD14+ monocytes from Fairfax et al. [51]. Fig. S1. Fraction of expression quantitative trait loci among the HIV-specific loci (see the Methods section for details) compared to all other loci. HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglycerides; SNP, single nucleotide polymorphism. CD14, CD14+ monocytes at baseline; INF, activated CD14+ monocytes following induction with interferon-γ; LPS2, activated CD14+ monocytes following a 2-h induction with lipopolysaccharide; LPS24, activated CD14+ monocytes following a 24-h induction with lipopolysaccharide. SNP, single nucleotide polymorphism.

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.

BackgroundDirect-acting antiviral (DAA) therapy have been shown to be highly successful in clinical trials and observational studies, but less is known about treatment success in patients with a high burden of comorbid conditions, including mental health and substance use disorders. We evaluated DAA effectiveness across a broad spectrum of patients with human immunodeficiency virus (HIV)-hepatitis C virus (HCV) coinfection in routine clinical care, including those with psychosocial comorbid conditions.MethodsThe primary end point was sustained virologic response (SVR), defined as HCV RNA not detected or 3.25) was present in 24%, and 17% were interferon treatment experienced; 96% had genotype 1 infection and 432 (81%) had received ledipasvir-sofosbuvir. SVR occurred in 96.5% (95% CI, 94.5%-97.9%). Patients who were black, treatment experienced, or cirrhotic all had SVR rates >95%. Patients with depression and/or anxiety, psychotic disorder, illicit drug use, or alcohol use disorder also had high SVR rates, ranging from 95.4% to 96.8%. The only factor associated with lower SVR rate was early discontinuation (77.8%; 95% CI, 52.4%-93.6%). Similar results were seen in multiply imputed data sets.ConclusionsOur study represents a large multicenter examination of DAA therapy in HIV/HCV-coinfected patients. The broad treatment success we observed across this diverse group of patients with significant comorbid conditions is highly affirming and argues for widespread implementation of DAA therapy.

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.

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 31930 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.

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 (

Substance use disorders (SUDs) are thought to predict care discontinuity, though magnitude and substance-specific variance of effects are unclear. This report of analytic work undertaken with a multi-regional American cohort of 9153 care enrollees addresses these gaps. Care retention was computed from 24-month post-linkage clinic visit documentation, with SUD cases identified from patient-report screening instruments. Two generalized estimating equations tested binary and hierarchial SUD predictors of retention, and potential effect modification by patient age-group, sex, and care site. Findings demonstrate: (1) detrimental SUD effect, equivalent to a nine percentage-point decrease in retention, with independent effects of age-group and care site; (2) substance-specific effect of marijuana UD associated with lower retention; and (3) age-modification of each effect on care discontinuity, with SUDs serving as a risk factor among 18-29 year-olds and protective factor among 60+ year-olds. Collective findings document patient attributes as influences that place particular subgroups at-risk to discontinue care.

Reducing racial/ethnic disparities in human immunodeficiency virus (HIV) disease is a high priority. Reductions in HIV racial/ethnic disparities can potentially be achieved by intervening on important intermediate factors. The potential population impact of intervening on intermediates can be evaluated using observational data when certain conditions are met. However, using standard stratification-based approaches commonly employed in the observational HIV literature to estimate the potential population impact in this setting may yield results that do not accurately estimate quantities of interest. Here we describe a useful conceptual and methodological framework for using observational data to appropriately evaluate the impact on HIV racial/ethnic disparities of interventions. This framework reframes relevant scientific questions in terms of a controlled direct effect and estimates a corresponding proportion eliminated. We review methods and conditions sufficient for accurate estimation within the proposed framework. We use the framework to analyze data on 2,329 participants in the CFAR [Centers for AIDS Research] Network of Integrated Clinical Systems (2008-2014) to evaluate the potential impact of universal prescription of and ≥95% adherence to antiretroviral therapy on racial disparities in HIV virological suppression. We encourage the use of the described framework to appropriately evaluate the potential impact of targeted interventions in addressing HIV racial/ethnic disparities using observational data.

Introduction: HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation. Methods: We included HIV treatment-na ıve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model. Results: The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL). Conclusions: In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.

Virally suppressed HIV-positive individuals on combination antiretroviral therapy who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality. The increased mortality was seen across different patient groups and for all causes of death

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.

Summary Associations of CD4:CD8 ratio or CD8 count with all-cause and cause-specific mortality were too small for them to be useful as independent prognostic markers in addition to CD4 count in virally suppressed patients on antiretroviral therapy with high CD4 count., Background We investigated whether CD4:CD8 ratio and CD8 count were prognostic for all-cause, AIDS, and non-AIDS mortality in virologically suppressed patients with high CD4 count. Methods We used data from 13 European and North American cohorts of human immunodeficiency virus–infected, antiretroviral therapy (ART)–naive adults who started ART during 1996–2010, who were followed from the date they had CD4 count ≥350 cells/μL and were virologically suppressed (baseline). We used stratified Cox models to estimate unadjusted and adjusted (for sex, people who inject drugs, ART initiation year, and baseline age, CD4 count, AIDS, duration of ART) all-cause and cause-specific mortality hazard ratios for tertiles of CD4:CD8 ratio (0–0.40, 0.41–0.64 [reference], >0.64) and CD8 count (0–760, 761–1138 [reference], >1138 cells/μL) and examined the shape of associations using cubic splines. Results During 276526 person-years, 1834 of 49865 patients died (249 AIDS-related; 1076 non-AIDS-defining; 509 unknown/unclassifiable deaths). There was little evidence that CD4:CD8 ratio was prognostic for all-cause mortality after adjustment for other factors: the adjusted hazard ratio (aHR) for lower vs middle tertile was 1.11 (95% confidence interval [CI], 1.00–1.25). The association of CD8 count with all-cause mortality was U-shaped: aHR for higher vs middle tertile was 1.13 (95% CI, 1.01–1.26). AIDS-related mortality declined with increasing CD4:CD8 ratio and decreasing CD8 count. There was little evidence that CD4:CD8 ratio or CD8 count was prognostic for non-AIDS mortality. Conclusions In this large cohort collaboration, the magnitude of adjusted associations of CD4:CD8 ratio or CD8 count with mortality was too small for them to be useful as independent prognostic markers in virally suppressed patients on ART.

Since the human immunodeficiency virus (HIV) epidemic began, several renal complications resulting from HIV infection of renal cells, immune dysregulation, and specific medications have been noted among individuals infected with HIV [1, 2]. The most severe of these, HIV-associated nephropathy (HIVAN), caused an estimated 35% of kidney lesions among HIV-infected patients biopsied during 1995–2004 [3] and was the fourth leading cause of end-stage renal disease (ESRD) among black individuals aged 20–64 years in 1994–1998 [4]. The incidence of HIVAN has declined with increased use of potent antiretroviral therapy (ART) [5–7]; however, there are other potential causes of ESRD in HIV-infected persons. Antiretroviral medications have renal effects including nephrotoxicity and stone formation [8]. Comorbidities such as diabetes mellitus, hypertension, and hepatitis C virus (HCV) infection are risk factors for progression to ESRD and are more common among HIV-infected persons [9–11]. Illicit drug use, which is more common among HIV-infected populations, also increases the risk of ESRD [12, 13]. Studies suggest that HIV-infected persons are more likely to experience ESRD than HIV-uninfected persons, with estimated incidence rates (IRs) in the US and Europe of 3–10 per 1000 person-years [14, 15] and 0.5 per 1000 PYs [16, 17], respectively, corresponding to a 2- to 20-fold greater risk compared with the general population. A large racial discrepancy has been noted in the burden of ESRD among HIV-infected and -uninfected individuals, with disproportionately higher risk borne by black individuals [17, 18]. Data from the United States Renal Data System (USRDS) indicated that the age- and sex-adjusted incidence of ESRD was approximately 3.4 times higher among blacks in the general population compared with whites in 2010 [19]. Whether reductions in the incidence of HIVAN have impacted the magnitude of the racial disparity in rates of ESRD among HIV-infected individuals is unknown. There is sparse information on the evolving face of ESRD in the HIV-infected population despite the significant burden of morbidity and mortality that ESRD presents [20–23]. Given the many potential contributors to ESRD risk, the goal of the present study was to assess the relative contributions of clinical and demographic factors to ESRD incidence and describe recent trends in ESRD risk in a cohort of HIV-infected individuals who are representative of HIV patients in care [24]. Our data, which include ESRD cases validated through an extensive medical record review of HIV-infected patients in clinical care through 2009, allowed us to capture changes in ESRD incidence concurrent with, and likely reflective of, modern therapy improvements. We hypothesized that well-documented improvements in HIV treatment in the modern therapy era have led to declines in risk of ESRD over this period, particularly among HIV-infected black individuals in care, given the diminishing role of HIVAN.

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.

Depression affects 20-30% of people with HIV. Randomized controlled trials (RCTs) have demonstrated the effectiveness of interventions to improve depression among HIV-infected adults, but typically have highly selected populations which may limit generalizability. Inverse probability of sampling weights (IPSW) are a recently proposed method to transport (or standardize) findings from RCTs to a specific external target population.

Background. There 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.

The strong association of CD4 count at start of combination therapy with subsequent survival in HIV-infected patients diminished during the first 5 years of treatment. After 5 years, lower baseline CD4 counts were not associated with higher mortality., Background. CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. Methods. We estimated mortality rates (MRs) by time since start of ART (

ObjectiveTo understand geographic variations in clinical retention, a central component of the HIV care continuum and key to improving individual- and population-level HIV outcomes.DesignWe evaluated retention by US region in a retrospective observational study.MethodsAdults receiving care from 2000–2010 in 12 clinical cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) contributed data. Individuals were assigned to Centers for Disease Control and Prevention (CDC)-defined regions by residential data (10 cohorts) and clinic location as proxy (2 cohorts). Retention was ≥2 primary HIV outpatient visits within a calendar year, >90 days apart. Trends and regional differences were analyzed using modified Poisson regression with clustering, adjusting for time in care, age, sex, race/ethnicity, and HIV risk, and stratified by baseline CD4+ count.ResultsAmong 78,993 adults with 444,212 person-years of follow-up, median time in care was 7 years (Interquartile Range: 4–9). Retention increased from 2000 to 2010: from 73% (5,000/6,875) to 85% (7,189/8,462) in the Northeast, 75% (1,778/2,356) to 87% (1,630/1,880) in the Midwest, 68% (8,451/12,417) to 80% (9,892/12,304) in the South, and 68% (5,147/7,520) to 72% (6,401/8,895) in the West. In adjusted analyses, retention improved over time in all regions (p

Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks.

Background Much of the prior research on viral failure (VF) with integrase inhibitor (INSTI) therapy is based on results from trials rather than clinical care settings and little is known about recently approved medications such as dolutegravir (DTG). We compared VF in persons living with HIV (PLWH) who initiated DTG-based vs. other guideline recommended regimens in clinical care across the United States. Methods PLWH from eight CFAR Network of Integrated Clinical Systems (CNICS) sites who started a recommended regimen between August 2013 and August 2016 were included. We compared DTG vs. other INSTI, and vs. darunavir-based (DRV) regimens included in current guidelines for initiating antiretroviral therapy (ART). VF was defined as a viral load of >400 copies/ml >6 months after initiation. We used Cox models adjusting for age, sex, race/ethnicity, hepatitis B, hepatitis C, tuberculosis, HIV risk factor, CD4 count, days since last HIV viral load, and site. PLWH were censored at death, regimen change or loss to follow-up (LTFU) with sensitivity analyses varying LTFU definitions from 0 to 12 months after last activity and including/excluding inverse probability censoring weights based on variables in the main models. Results Among 6636 PLWH who initiated a recommended regimen, a lower proportion on DTG-based regimens experienced VF during follow-up (Figure). The adjusted hazard ratio (HR) for VF for DTG vs. DRV-based regimens was 0.56 (95% confidence interval 0.37–0.86). In sensitivity models, the HR for VF for DTG vs. other INSTI regimens ranged from 0.73 to 1.07 depending on LTFU definitions. The HR for DTG vs. DRV-based regimens ranged from 0.38 to 0.63 depending on LTFU definitions. In sensitivity analyses among the 1,229 PLWH known to be ART-naive at initiation, a similar pattern was found with a lower HR of VF among those who initiated DTG vs. DRV-based regimens (HR 0.25, 95% CI 0.11–0.56). Conclusion The observed rate of VF during follow-up was lower among PLWH initiating DTG-based vs. DRV-based regimens in routine clinical care at sites across the US. Results also demonstrated that different definitions of LTFU can have a large impact on the results and highlight the importance of sensitivity analyses in informing study definitions to minimize bias. Figure. Kapxlan–Meier curve of time to VF. Disclosures V. Vannappagari, ViiV Healthcare: Employee and Shareholder, Salary and Stocks; K. Smith, ViiV Healthcare: Employee, Salary; C. Johannes, VIIV: Research Contractor, Research support; B. Calingaert, VIIV: Research Contractor, Research support; C. Saltus, VIIV: Research Contractor, Research grant; J. Eron, VIIV: Scientific Advisor, Consulting fee; M. S. Saag, VIIV: Grant Investigator and Scientific Advisor, Grant recipient; BMS: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient; Gilead: Grant Investigator and Scientific Advisor, Consulting fee and Research support; Merck: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient; H. M. Crane, VIIV: Scientific Advisor, Nothing to date but I have been asked to be an advisor so there may be a relationship in the future.

BackgroundThe incidence of non-Hodgkin lymphoma (NHL) in human immunodeficiency virus (HIV)-infected patients remains high despite treatment with antiretroviral therapy (ART).MethodsWe evaluated NHL incidence in HIV-infected patients followed in the Centers for AIDS Research Network of Integrated Clinical Systems who started combination ART and achieved suppression of HIV. We estimated the hazard ratio for NHL by time-varying HIV viremia categories, accounting for time-varying CD4 cell count using marginal structural models.ResultsWe observed 37 incident NHL diagnoses during 21 607 person-years of follow-up in 6036 patients (incidence rate, 171 per 100 000 person-years; 95% confidence interval [CI], 124-236). NHL incidence was high even among patients with nadir CD4 cell count >200 cells/µL (140 per 100 000 person-years [95% CI, 80-247]). Compared with ≤50 copies/mL, hazard ratios (HRs) for NHL were higher among those with HIV viremia of 51-500 copies/mL (HR current = 1.66 [95% CI, .70-3.94]; HR 3-month lagged = 2.10 [95% CI, .84-5.22]; and HR 6-month lagged = 1.46 [95% CI, .60-3.60]) and >500 copies/mL (HR current = 2.39 [95% CI, .92-6.21]; HR 3-month lagged = 3.56 [95% CI, 1.21-10.49]; and HR 6-month lagged = 2.50 [95% CI, .91-6.84]). Current HIV RNA as a continuous variable was also associated with NHL (HR = 1.42 per log10 copies/mL [95% CI, 1.05-1.92]).ConclusionsOur findings demonstrate a high incidence of NHL among HIV-infected patients on ART and suggest a role of HIV viremia in the pathogenesis of NHL. Earlier initiation of potent ART and maximal continuous suppression of HIV viremia may further reduce NHL risk.

BackgroundDespite widespread use in HIV and hepatitis B virus (HBV) infection, the effectiveness of tenofovir (TDF) has not been studied extensively outside of small cohorts of coinfected patients with HBV-HIV. We examined the effect of prior lamivudine (3TC) treatment and other factors on HBV DNA suppression with TDF in a multisite clinical cohort of coinfected patients.MethodsWe studied all patients enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort from 1996 to 2011 who had chronic HBV and HIV infection, initiated a TDF-based regimen continued for ≥ 3 months and had on-treatment HBV DNA measurements. We used Kaplan-Meier curves and Cox-proportional hazards to estimate time to suppression (HBV DNA level 10,000 IU/mL, and lower nadir CD4 count were independently associated with decreased likelihood of HBV DNA suppression on TDF.ConclusionsThese results emphasize the role of prior 3TC exposure and immune response on delayed HBV suppression on TDF.

Among HIV-infected patients who initiated antiretroviral therapy (ART), patterns of cause-specific death varied by ART duration and were strongly related to age, sex, and transmission risk group. Deaths from non-AIDS malignancies were much more frequent than those from cardiovascular disease., Background. Patterns of cause-specific mortality in individuals infected with human immunodeficiency virus type 1 (HIV-1) are changing dramatically in the era of antiretroviral therapy (ART). Methods. Sixteen cohorts from Europe and North America contributed data on adult patients followed from the start of ART. Procedures for coding causes of death were standardized. Estimated hazard ratios (HRs) were adjusted for transmission risk group, sex, age, year of ART initiation, baseline CD4 count, viral load, and AIDS status, before and after the first year of ART. Results. A total of 4237 of 65 121 (6.5%) patients died (median, 4.5 years follow-up). Rates of AIDS death decreased substantially with time since starting ART, but mortality from non-AIDS malignancy increased (rate ratio, 1.04 per year; 95% confidence interval [CI], 1.0–1.1). Higher mortality in men than women during the first year of ART was mostly due to non-AIDS malignancy and liver-related deaths. Associations with age were strongest for cardiovascular disease, heart/vascular, and malignancy deaths. Patients with presumed transmission through injection drug use had higher rates of all causes of death, particularly for liver-related causes (HRs compared with men who have sex with men: 18.1 [95% CI, 6.2–52.7] during the first year of ART and 9.1 [95% CI, 5.8–14.2] thereafter). There was a persistent role of CD4 count at baseline and at 12 months in predicting AIDS, non-AIDS infection, and non-AIDS malignancy deaths. Lack of viral suppression on ART was associated with AIDS, non-AIDS infection, and other causes of death. Conclusions. Better understanding of patterns of and risk factors for cause-specific mortality in the ART era can aid in development of appropriate care for HIV-infected individuals and inform guidelines for risk factor management.

BackgroundCompared to uninfected people, human immunodeficiency virus (HIV)-infected individuals may have an increased risk of acute myocardial infarction (AMI). Currently, HIV-infected people are treated to the same blood pressure (BP) goals (

BackgroundContemporary data on patterns of antiretroviral therapy (ART) use in the United States are needed to inform efforts to improve the HIV care cascade.MethodsWe conducted a cross-sectional study of patients in the Centers for AIDS Research Network of Integrated Clinical Systems cohort who were in HIV care in 2010 to assess ART use and outcomes, stratified by nadir CD4 count (≤350, 351-500, or >500 cells/mm), demographics, psychiatric diagnoses, substance use, and engagement in continuous care (≥2 visits ≥3 months apart in 2010).ResultsOf 8633 patients at 7 sites who had ≥1 medical visit and ≥1 viral load in 2010, 94% had ever initiated ART, 89% were on ART, and 70% had an undetectable viral load at the end of 2010. Fifty percent of ART-naive patients had nadir CD4 counts >500 cells per cubic millimeter, but this group comprised just 3% of the total population. Among patients who were ART naive at the time of cohort entry (N = 4637), both ART initiation and viral suppression were strongly associated with nadir CD4 count. Comparing 2009 and 2010, the percentages of patients with viral suppression among those with nadir CD4 counts 351-500 and >500 cells per cubic millimeter were 44% vs. 57% and 25% vs. 33%, respectively. Engagement in care was the only factor consistently associated with ART use and viral suppression across nadir CD4 count strata.ConclusionsOur findings suggest that ART use and viral suppression among persons in HIV care may be more common than estimated in some previous studies and increased from 2009 to 2010.

We assessed laboratory monitoring after combination antiretroviral therapy initiation among 3678 patients in a large US multisite clinical cohort, censoring participants at last clinic visit, combination antiretroviral therapy change, or 3 years. Median days (interquartile range) to first hematologic, hepatic, renal, and lipid tests were 30 (18-53), 31 (19-56), 33 (20-59), and 350 (96-1106), respectively. At 1 year, approximately 80% received more than 2 hematologic, hepatic, and renal tests consistent with guidelines. However, only 40% received 1 or more lipid tests. Monitoring was more frequent in specific subgroups, likely reflecting better clinic attendance or clinician perception of higher susceptibility to toxicities.

ObjectiveHIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic human papillomavirus infection-the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women.MethodsData were obtained from HIV-infected and -uninfected female participants in the North American AIDS Cohort Collaboration on Research and Design with no history of ICC at enrollment. Participants were followed from study entry or January 1996 through ICC, loss to follow-up, or December 2010. The relationship of HIV infection and CD4+ T-cell count with risk of ICC was assessed using age-adjusted Poisson regression models and standardized incidence ratios. All cases were confirmed by cancer registry records and/or pathology reports. Cervical cytology screening history was assessed through medical record abstraction.ResultsA total of 13,690 HIV-infected and 12,021 HIV-uninfected women contributed 66,249 and 70,815 person-years of observation, respectively. Incident ICC was diagnosed in 17 HIV-infected and 4 HIV-uninfected women (incidence rate of 26 and 6 per 100,000 person-years, respectively). HIV-infected women with baseline CD4+ T-cells of ≥350, 200-349, and

BackgroundThe U.S. National HIV/AIDS Strategy targets for 2015 include "increasing access to care and improving health outcomes for persons living with HIV in the United States" (PLWH-US).ObjectiveTo demonstrate the utility of the NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) for monitoring trends in the HIV epidemic in the United States and to present trends in HIV treatment and related health outcomes.DesignTrends from annual cross-sectional analyses comparing patients from pooled, multicenter, prospective, clinical HIV cohort studies with PLWH-US, as reported to national surveillance systems in 40 states.SettingU.S. HIV outpatient clinics.PatientsHIV-infected adults with 1 or more HIV RNA plasma viral load (HIV VL) or CD4 T-lymphocyte (CD4) cell count measured in any calendar year from 1 January 2000 to 31 December 2008.MeasurementsAnnual rates of antiretroviral therapy use, HIV VL, and CD4 cell count at death.Results45 529 HIV-infected persons received care in an NA-ACCORD-participating U.S. clinical cohort from 2000 to 2008. In 2008, the 26 030 NA-ACCORD participants in care and the 655 966 PLWH-US had qualitatively similar demographic characteristics. From 2000 to 2008, the proportion of participants prescribed highly active antiretroviral therapy increased by 9 percentage points to 83% (P < 0.001), whereas the proportion with suppressed HIV VL (≤2.7 log10 copies/mL) increased by 26 percentage points to 72% (P < 0.001). Median CD4 cell count at death more than tripled to 0.209 × 109 cells/L (P < 0.001).LimitationThe usual limitations of observational data apply.ConclusionThe NA-ACCORD is the largest cohort of HIV-infected adults in clinical care in the United States that is demographically similar to PLWH-US in 2008. From 2000 to 2008, increases were observed in the percentage of prescribed HAART, the percentage who achieved a suppressed HIV VL, and the median CD4 cell count at death.Primary funding sourceNational Institutes of Health; Centers for Disease Control and Prevention; Canadian Institutes of Health Research; Canadian HIV Trials Network; and the government of British Columbia, Canada.

Adherence to antiretroviral therapy (ART) is critical for successful treatment of Human Immunodeficiency Virus (HIV), but comparisons across settings are difficult because adherence is measured in different ways. We examined utility of different adherence measures for identification of patients at risk of viral failure (VF). Eight cohorts in the ART Cohort Collaboration contributed data from pharmacy refills or self-report questionnaires collected between 1996 and 2013 (N = 11689). For pharmacy data (N = 7156), we examined associations of percentage adherence during the 1st year of ART with VF (>500 copies/mL) at 1 year. For self-report data (N = 4533), we examined 28-day adherence with VF based on closest viral load measure within 6 months after questionnaire date. Since adherence differed markedly by measurement type, we defined different cut-off points for pharmacy (lower

Background The consequences of substance use disorders (SUDs) are varied and broad, affecting many sectors of society and the economy. Economic evaluation translates these consequences into dollars to examine the net economic impact of interventions for SUD, and associated conditions such as HCV and HIV. The nexus between substance use and crime makes criminal justice outcomes particularly significant for estimating the economic impact of SUD interventions, and important for data harmonization. Methods We compared baseline data collected in six NIDA-funded Seek, Test, Treat and Retain (STTR) intervention studies that enrolled HIV-infected/at-risk individuals with SUDs (total n = 3415). Criminal justice measures included contacts with the criminal justice system (e.g., arrests) and criminal offenses. The objective was to develop a list of recommended measures and methods supporting economic data harmonization opportunities in HIV and SUD research, with an initial focus on crime-related outcomes. Results Criminal justice contacts and criminal offenses were highly variable across studies. When measures grouped by offense classifications were compared, consistencies across studies emerged. Most individuals report being arrested for property or public order crimes (> 50%); the most commonly reported offenses were prostitution/pimping, larceny/shoplifting, robbery, and household burglary. Conclusions We identified four measures that are feasible and appropriate for estimating the economic consequences of SUDs/HIV/HCV: number of arrests, number of convictions, days of incarceration, and times committing criminal offenses, by type of offense. To account for extreme variation, grouping crimes by offense classification or calculating monthly averages per event allows for more meaningful comparisons across studies.