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Ancillary service needs likely influence time to diagnosis and presentation for HIV care. The effect of both met and unmet needs on late presentation to HIV care is not well understood. We used baseline data from 348 people with HIV (PWH) with no prior HIV care who enrolled in iENGAGE (a randomized controlled trial (RCT) of an intervention to support retention in care) at one of four HIV clinics in the US. A standardized baseline questionnaire collected information on ancillary service needs, and whether each need was presently unmet. We examined covariates known to be associated with disease stage at presentation to care and their association with needs. We subsequently assessed the relationship of needs with CD4 accounting for those other covariates by estimating prevalence ratios (PR) using inverse probability weights. Most patients enrolling in the RCT were male (79%) and the majority were Black (62%); median age was 34 years. Prevalence of any reported individual need was 69%. One-third of the sample had a baseline CD4 cell count <200, 42% between 200 and 499 and 27% ≥500. There was no statistically significant association between need or unmet need and baseline CD4. In general, psychiatric health and SU issues (depression, anxiety, and drug use) were consistently associated with higher prevalence of need (met and unmet). Additionally, the Black race was associated with higher basic resource needs (housing: PR 1.67, 95%CI 1.08-2.59; transportation: PR 1.65, 95% CI 1.12-2.45). Ancillary service needs (met and unmet) were common among patients new to HIV care and impacted vulnerable subgroups. However, we found no evidence that reporting a specific individual need, whether met or unmet, was associated with a timely presentation to HIV care. The impact of needs on subsequent steps of the HIV care continuum will be examined with longitudinal data.

Many people living with HIV (PLWH) pass through correctional facilities each year, a large proportion of whom do not maintain viral suppression following release. We examined the effects of imPACT, an intervention designed to promote post-release viral suppression, on antiretroviral therapy (ART) adherence. PLWH awaiting release from prisons in two southern states were randomized to imPACT (consisting of motivational interviewing, care linkage coordination, and text message medication reminders) versus standard care (SC). ART adherence, measured by unannounced monthly telephone pill counts, was compared between study arms over 6 months post-release. Of 381 participants eligible for post-release follow-up, 302 (79%) completed ≥ 1 of 6 possible pill counts (median: 4; IQR 1-6). Average adherence over follow-up was 80.3% (95% CI 77.5, 83.1) and 81.0% (78.3, 83.6) of expected doses taken in the imPACT and SC arms, respectively. There was no difference between arms when accounting for missing data using multiple imputation (mean difference = - 0.2 percentage points [- 3.7, 3.3]), controlling for study site and week of follow-up. Of the 936 (40.9%) pill counts that were missed, 212 (22.7%) were due to re-incarceration. Those who missed pill counts for any reason were more likely to be unsuppressed, suggesting that they had lower adherence. However, missingness was balanced between arms. Among PLWH released from prison, ART adherence averaged > 80% in both study arms over 6 months-a level higher than seen with most other chronic diseases. However, missing data may have led to an overestimate of adherence. Factors independent of the intervention influence ART adherence in this population and should be identified to inform future targeted interventions.

Depression is a known risk factor for antiretroviral therapy (ART) non-adherence, but little is known about the mechanisms explaining this relationship. Identifying these mechanisms among people living with HIV (PLHIV) after release from prison is particularly important, as individuals during this critical period are at high risk for both depression and poor ART adherence. 347 PLHIV recently released from prison in North Carolina and Texas were included in analyses to assess mediation of the relationship between depressive symptoms at 2 weeks post-release and ART adherence (assessed by unannounced telephone pill counts) at weeks 9-21 post-release by the hypothesized explanatory mechanisms of alcohol use, drug use, adherence self-efficacy, and adherence motivation (measured at weeks 6 and 14 post-release). Indirect effects were estimated using structural equation models with maximum likelihood estimation and bootstrapped confidence intervals. On average, participants achieved 79% ART adherence. The indirect effect of depression on adherence through drug use was statistically significant; greater symptoms of depression were associated with greater drug use, which was in turn associated with lower adherence. Lower adherence self-efficacy was associated with depressive symptoms, but not with adherence. Depression screening and targeted mental health and substance use services for depressed individuals at risk of substance use constitute important steps to promote adherence to ART after prison release.

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

Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/μl compared with 500 cells/μl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size., (© 2019 John Wiley & Sons, Ltd.)

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

Background: People living with HIV (PLWH) 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)., Methods: Participants 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., Results: Of 433 PLWH and chronic pain, 28% reported marijuana use in the past 3 months. Median pain severity at the index visit was 6.3/10 (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., Conclusions: We did not find evidence that marijuana use in PLWH is associated with improved pain outcomes or reduced opioid prescribing. This suggests that caution is warranted when counseling PLWH about potential benefits of recreational or medical marijuana.

Background: Engagement 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 Methods: Using 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., Results: Results 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., Conclusions: The 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.

Objective: Characterize virologic and immunologic outcomes of INSTI-based antiretroviral therapy (ART) in experienced patients with and without virologic failure., Design: Prospective clinical cohort., Methods: ART-experienced, INSTI-naive participants in the University of North Carolina Center for AIDS Research HIV Clinical Cohort (UCHCC) initiating an INSTI-containing regimen 2007-2016 were followed from INSTI initiation (baseline) to the earliest of: outcome of interest, loss to follow-up (LTFU, 1 year without clinical visit), or death. Outcomes of interest were virologic failure (first of two consecutive viral loads at least 200 copies/ml more than 2 weeks apart, or one viral load ≥200 before LTFU) and immune recovery (first CD4 ≥500 cells/μl). Patients with baseline viral load at least 50 copies/ml were given 24 weeks before meeting virologic failure criteria. Kaplan-Meier curves and Cox proportional hazards models compared INSTI regimens and patient characteristics., Results: Of 773 patients, 32% were women, 59% African-American, and 42% had a viral load at least 50 copies/ml at INSTI initiation. After 2 years, 5% of patients with baseline viral load less than 50 copies/ml experienced virologic failure, compared with 35% of patients with baseline viral load at least 50 copies/ml (P < 0.01). Among patients with baseline viral load less than 50 copies/ml, dolutegravir/NRTIs was associated with longer time to virologic failure [adjusted hazard ratio (aHR) 0.11, 95% confidence interval (CI) 0.01-0.80], whereas among patients with baseline viral load at least 50 copies/ml, raltegravir/NRTIs was associated with longer time to virologic failure (aHR 0.35, 95% CI 0.18-0.68), both compared with elvitegravir/NRTIs. After 5 years suppressed, irrespective of baseline viral load, 61% of patients experienced immune recovery., Conclusion: In this cohort, INSTI-containing regimens led to low virologic failure rates in patients switching ART while suppressed. Viremic patients initiating INSTIs were at high risk of virologic failure during follow-up.

Objective: The aim of this study was to evaluate postpartum HIV care outcomes., Design: A prospective clinical cohort of women with HIV and a live birth at the University of North Carolina, 1996-2014., Methods: We estimated two stages of the HIV care continuum in the first 24 months postpartum: care retention (at least two visits per year, ≥90 days apart) and viral suppression (HIV RNA < 400 copies/ml). Multivariable models were fit using logistic regression., Results: Among 1416 women, 141 experienced a live birth at a median age of 28 years, with 74% virally suppressed at delivery. Among all women, 48% were retained in care and 25% maintained viral suppression for the first 24 months postpartum. Among women with available HIV RNA measures, 42% were suppressed at 24 months. HIV care retention estimates were stable across calendar years, but viral suppression rates at 24 months postpartum, among women with available HIV RNA measures, increased from 33 to 67% from 1996-2001 to 2009-2014 (P = 0.04). Being at least 30 years old was positively, and receiving less than 12 weeks of antenatal antiretroviral therapy was negatively, associated with HIV care retention at 24 months postpartum [adjusted odds ratio (AOR): 2.41, 95% confidence interval (95% CI): 1.09-5.29 and AOR: 0.27, 95% CI: 0.08-0.86]. Older maternal age and viral suppression at delivery were both positively associated with virologic suppression at 24 months postpartum (AOR: 2.52, CI: 1.02-6.22, and AOR: 6.42 CI: 1.29-31.97, respectively)., Conclusion: HIV care continuum outcomes decrease substantially postpartum, with younger women and those with less antenatal HIV care less likely to successfully remain engaged in HIV care following childbirth.

Purpose: To assess sampling bias in national viral suppression (VS) estimates derived from the Medical Monitoring Project (MMP) resulting from use of an abbreviated (four-month) annual sampling period. We aimed to improve VS estimates using cohort data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and a novel cohort-adjustment method., Methods: Using full calendar years of NA-ACCORD data, we assessed timing of HIV care attendance (inside vs. exclusively outside MMP's four-month sampling period), VS status at last test (<200 vs. ≥200 copies/mL), and associated demographics. These external estimates were used to standardize MMP to NA-ACCORD data with multivariable regression models of care attendance and VS, yielding adjusted 2009-2013 VS estimates with 95% confidence intervals., Results: Weighted percentages of VS among persons in HIV care were 67% in 2009 and 77% in 2013. These estimates are slightly lower than previously published MMP estimates (72% and 80% in 2009 and 2013, respectively). The number of persons receiving HIV care was previously underestimated by 20%, because patients receiving care exclusively outside the MMP sampling period did not contribute toward the weighted population estimate., Conclusions: Careful examination of national surveillance estimates using data triangulation and novel methodologies can improve the robustness of VS estimates., (Published by Elsevier Inc.)

Background: Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes., Methods: We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes. Traditional risk factors were tobacco smoking, hypertension, elevated total cholesterol, type 2 diabetes, renal impairment (stage 4 chronic kidney disease), and hepatitis C virus and hepatitis B virus infections. HIV-related risk factors were low CD4 count (<200 cells per μL), detectable plasma HIV RNA (>400 copies per mL), and history of a clinical AIDS diagnosis. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented., Findings: In each of the study populations for the four outcomes (1405 of 61 500 had non-AIDS-defining cancer, 347 of 29 515 had myocardial infarctions, 387 of 35 044 had end-stage liver disease events, and 255 of 35 620 had end-stage renal disease events), about 17% were older than 50 years at study entry, about 50% were non-white, and about 80% were men. Preventing smoking would avoid 24% (95% CI 13-35) of these cancers and 37% (7-66) of the myocardial infarctions. Preventing elevated total cholesterol and hypertension would avoid the greatest proportion of myocardial infarctions: 44% (30-58) for cholesterol and 42% (28-56) for hypertension. For liver disease, the PAF was greatest for hepatitis C infection (33%; 95% CI 17-48). For renal disease, the PAF was greatest for hypertension (39%; 26-51) followed by elevated total cholesterol (22%; 13-31), detectable HIV RNA (19; 9-31), and low CD4 cell count (13%; 4-21)., Interpretation: The substantial proportion of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes that could be prevented with interventions on traditional risk factors elevates the importance of screening for these risk factors, improving the effectiveness of prevention (or modification) of these risk factors, and creating sustainable care models to implement such interventions during the decades of life of adults living with HIV who are receiving care., Funding: National Institutes of Health, US Centers for Disease Control and Prevention, the US Agency for Healthcare Research and Quality, the US Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long Term Care, and the Government of Alberta., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The effect of depressive symptoms on progression through the human immunodeficiency virus (HIV) treatment cascade is poorly characterized., Methods: We included participants from the Centers for AIDS Research Network of Integrated Clinic Systems cohort who were antiretroviral therapy (ART) naive, had at least 1 viral load and HIV appointment measure after ART initiation, and a depressive symptom measure within 6 months of ART initiation. Recent depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and categorized using a validated cut point (PHQ-9 ≥10). We followed participants from ART initiation through the first of the following events: loss to follow-up (>12 months with no HIV appointment), death, administrative censoring (2011-2014), or 5 years of follow-up. We used log binomial models with generalized estimating equations to estimate associations between recent depressive symptoms and having a detectable viral load (≥75 copies/mL) or missing an HIV visit over time., Results: We included 1057 HIV-infected adults who contributed 2424 person-years. At ART initiation, 30% of participants reported depressive symptoms. In multivariable analysis, recent depressive symptoms increased the risk of having a detectable viral load (risk ratio [RR], 1.28; 95% confidence interval [CI], 1.07, 1.53) over time. The association between depressive symptoms and missing an HIV visit (RR, 1.20; 95% CI, 1.05, 1.36) moved to the null after adjustment for preexisting mental health conditions (RR, 1.00; 95% CI, 0.85, 1.18)., Conclusions: Recent depressive symptoms are a risk factor for unsuppressed viral load, while preexisting mental health conditions may influence HIV appointment adherence.

Background: We estimated the effect of initiating virologically suppressive antiretroviral therapy (ART) during acute HIV infection versus chronic HIV infection (AHI vs. CHI) on CD4/CD8 ratio normalization., Setting: A prospective clinical cohort study., Methods: We included patients initiating ART with AHI and CHI between 2000 and 2015 and compared time from ART initiation to the first normal CD4/CD8 ratio (defined as CD4/CD8 ≥1) using Kaplan-Meier curves and multivariable Cox proportional hazards models. Patient time was censored at virologic failure, lost to follow-up, or death. We also characterized CD4, CD8, and CD4/CD8 trajectories over the first 3 years of ART., Results: The 1198 patients were 27% female and 60% African American, with a median age of 37 years (interquartile range 28-47) at ART initiation. The 83 AHI patients were more likely male, younger, and of white race, than CHI patients. After 2 years of suppressive ART, 70% of AHI patients achieved a normal CD4/CD8 ratio, compared to 6%-38% of CHI patients, with greater likelihood of normalization at higher baseline CD4 counts. Time to normalization was shortest among AHI patients, followed by CHI patients with higher baseline CD4. The adjusted hazard ratio for time to normalization for AHI patients compared to CHI patients with baseline CD4 >350 was 4.33 (95% CI: 3.16 to 5.93). Higher baseline CD4/CD8 ratio was also associated with time to normalization (adjusted hazard ratio 1.54; 1.46, 1.63, per 0.1 increase in ratio)., Conclusions: Initiating ART during AHI at higher baseline CD4 cell counts and CD4/CD8 ratios was associated with shorter time to CD4/CD8 ratio normalization.

Objective: To estimate the prevalence of HIV drug resistance over time and identify risk factors for multiclass resistance., Design: Prospective clinical cohort of HIV-infected patients at the University of North Carolina., Methods: Among antiretroviral therapy (ART)-experienced patients in care 2000-2016, we estimated annual prevalences of cumulative resistance, defined as at least one major mutation by drug class. Clinical data and multiple imputation were used when genotypic data were missing, and mutations were carried forward in time. We estimated resistance odds ratios comparing characteristics of patients in care in 2016., Results: A total of 3682 patients contributed 23 169 person-years. Prevalence of at least one major resistance mutation, irrespective of viral suppression, peaked in 2005 with 49% (95% confidence interval 46, 52) and decreased to 38% (35, 40) in 2016. Resistance to nucleoside reverse transcriptase inhibitors, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors also peaked in 2005-2007 and decreased to 28 (26, 31), 14 (12, 16), and 27% (24, 29) in 2016, respectively. In 2016, prevalence of integrase strand transfer inhibitor (INSTI) resistance was 2% (1, 3) and triple-class resistance 10% (9, 12). Over the study period, cumulative resistance was frequent among patients with detectable viremia, but uncommon among patients initiating ART post-2007. Among 1553 patients in care in 2016, ART initiation at an older age, with an INSTI, and with higher CD4 cell counts were associated with resistance to fewer or no classes., Conclusion: Prevalence of resistance to older ART classes has decreased in the last 10 years in this clinical cohort, whereas INSTI resistance has increased but remained very low. Patients with viremia continue to have a high burden of resistance even if they initiated ART recently.

Background: Because HIV viral suppression is essential for optimal outcomes and prevention efforts, understanding trends and predictors is imperative to inform public health policy., Objective: To 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., Design: Longitudinal observational cohort study., Setting: 8 HIV clinics across the United States., Participants: PLWH receiving clinical care., Measurements: To 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., Results: Viral 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., Limitation: Results are limited to PLWH receiving clinical care., Conclusion: HIV 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 Source: National Institutes of Health.

Background: Chronic 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., Methods: This 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., Results: Among 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)., Conclusions: Chronic 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.

We use a socioecological model of health to define resilience, review the definition and study of resilience among persons living with human immunodeficiency virus (PLWH) in the existing peer-reviewed literature, and discuss the strengths and limitations of how resilience is defined and studied in HIV research. We conducted a review of resilience research for HIV-related behaviors/outcomes of antiretroviral therapy (ART) adherence, clinic attendance, CD4 cell count, viral load, viral suppression, and/or immune functioning among PLWH. We performed searches using PubMed, PsycINFO and Google Scholar databases. The initial search generated 14,296 articles across the three databases, but based on our screening of these articles and inclusion criteria, n = 54 articles were included for review. The majority of HIV resilience research defines resilience only at the individual (i.e., psychological) level or studies individual and limited interpersonal resilience (e.g., social support). Furthermore, the preponderance of HIV resilience research uses general measures of resilience; these measures have not been developed with or tailored to the needs of PLWH. Our review suggests that a socioecological model of health approach can more fully represent the construct of resilience. Furthermore, measures specific to PLWH that capture individual, interpersonal, and neighborhood resilience are needed.

Background: Transmitted drug resistance (TDR) compromises clinical management and outcomes. Transmitted drug resistance surveillance and identification of growing transmission clusters are needed in the Southeast, the epicenter of the US HIV epidemic. Our study investigated prevalence and transmission dynamics in North Carolina., Methods: We analyzed surveillance drug resistance mutations (SDRMs) using partial pol sequences from patients presenting to 2 large HIV outpatient clinics from 1997 to 2014. Transmitted drug resistance prevalence was defined as ≥1 SDRMs among antiretroviral therapy (ART)-naïve patients. Binomial regression was used to characterize prevalence by calendar year, drug class, and demographic and clinical factors. We assessed the transmission networks of patients with TDR with maximum likelihood trees and Bayesian methods including background pol sequences (n = 15 246)., Results: Among 1658 patients with pretherapy resistance testing, ≥1 SDRMs was identified in 199 patients, with an aggregate TDR prevalence of 12% (95% confidence interval, 10% to 14%) increasing over time ( P = .02). Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs; 8%) was common, followed by nucleoside reverse transcriptase inhibitors (4%) and protease inhibitors (2%). Factors associated with TDR were being a man reporting sex with men, white race, young age, higher CD4 cell count, and being a member of a transmission cluster. Transmitted drug resistance was identified in 106 clusters ranging from 2 to 26 members. Cluster resistance was primarily NNRTI and dominated by ART-naïve patients or those with unknown ART initiation., Conclusions: Moderate TDR prevalence persists in North Carolina, predominantly driven by NNRTI resistance. Most TDR cases were identified in transmission clusters, signifying multiple local transmission networks and TDR circulation among ART-naïve persons. Transmitted drug resistance surveillance can detect transmission networks and identify patients for enhanced services to promote early treatment.

Background: Our aim was to describe alcohol consumption trajectories in a cohort of people living with HIV and determine clinical and sociodemographic predictors of each trajectory., Methods: This 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., Results: We 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., Conclusions: Longitudinal trajectories of increasing alcohol use and stable misuse highlight the need to integrate routine screening and alcohol misuse interventions into HIV primary care., (Copyright © 2017 by the Research Society on Alcoholism.)

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., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

OBJECTIVE Burn patients are particularly vulnerable to infection, and an estimated half of all burn deaths are due to infections. This study explored risk factors for healthcare-associated infections (HAIs) in adult burn patients. DESIGN Retrospective cohort study. SETTING Tertiary-care burn center. PATIENTS Adults (≥18 years old) admitted with burn injury for at least 2 days between 2004 and 2013. METHODS HAIs were determined in real-time by infection preventionists using Centers for Disease Control and Prevention criteria. Multivariable Cox proportional hazards regression was used to estimate the direct effect of each risk factor on time to HAI, with inverse probability of censor weights to address potentially informative censoring. Effect measure modification by burn size was also assessed. RESULTS Overall, 4,426 patients met inclusion criteria, and 349 (7.9%) patients had at least 1 HAI within 60 days of admission. Compared to 6 times as likely to acquire an HAI (HR, 6.38; 95% CI, 3.64-11.17); and patients with >20% TBSA were >10 times as likely to acquire an HAI (HR, 10.33; 95% CI, 5.74-18.60). Patients with inhalational injury were 1.5 times as likely to acquire an HAI (HR, 1.61; 95% CI, 1.17-2.22). The effect of inhalational injury (P=.09) appeared to be larger among patients with ≤20% TBSA. CONCLUSIONS Larger burns and inhalational injury were associated with increased incidence of HAIs. Future research should use these risk factors to identify potential interventions. Infect Control Hosp Epidemiol 2017;38:1441-1448.

Antiretroviral (ARV) adherence has largely been considered from the perspective of an individual's behavior with less attention given to potential structural causes for lapses in treatment, such as the cost of medications and care. HIV medication expense is typically covered by third party payers. However, private insurance premiums and deductibles may rise, or policies terminated such as with a change in employment. Likewise, a patient's eligibility for publicly funded coverage like state AIDS Drug Assistance Programs (ADAP) or Medicaid can also be lost. We conducted a one-time survey of a sample of 300 patients receiving HIV care at a single large academic center in the south of United States to examine lapses in HIV therapy due to financial reasons. We found that during the prior year, financial issues including medication cost or coverage led to a lapse in ARVs in 10% (n = 31) of participants. However, of the 42% (n = 125) participants who had been enrolled in ADAP at any time during the prior year, 21% (n = 26) reported an ARV lapse due to problems with ADAP or medication cost. Respondents cited ADAP's required semi-annual renewal process and other administrative issues as the cause of ARV lapses. The median duration of missed ARVs was 2 weeks (range of <1-23 weeks). Non-HIV medication and transportation to and from clinic costs were also identified as financial burdens to care by respondents. In conclusion, although conducted at a single medical center and one state, this study suggests that a significant minority of HIV-infected patients encounter financial barriers to ARV access, and this is paradoxically more common among those enrolled in the state ADAP. Streamlining, supporting, and simplifying ADAP renewal procedures will likely reduce lapses in ARV adherence and persistence.

Background: Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic responses with initial ART according to the class of anchor agent used., Setting: An observational clinical cohort study in the Southeastern United States., Methods: All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included. Separate time-to-event analyses with regimen discontinuation and virologic failure as outcomes were used, including Kaplan-Meier survival curves and adjusted Cox proportional hazards models., Results: One thousand six hundred twenty-four patients were included (median age of 37 years at baseline, 28% women, 60% African American, and 28% white). Eleven percent initiated integrase strand transfer inhibitor (INSTI), 33% non-nucleoside reverse transcriptase inhibitor (NNRTI), 20% boosted protease inhibitor, 27% other, and 9% NRTI only regimens. Compared with NNRTI-containing regimens, INSTI-containing regimens had an adjusted hazard ratio of 0.49 (95% confidence interval, 0.35 to 0.69) for discontinuation and 0.70 (95% confidence interval, 0.46 to 1.06) for virologic failure. All other regimen types were associated with increased rates of discontinuation and failure compared with NNRTI., Conclusions: Initiating ART with an INSTI-containing regimen was associated with lower rates of regimen discontinuation and virologic failure.

Background: Delaying HIV care initiation may lead to greater morbidity, mortality, and further HIV transmission. Rural residence may be associated with delayed diagnosis and linkage to care, with negative clinical outcomes., Objective: To examine the association between rural patient residence and CD4 cell count at HIV care initiation in a large HIV clinical cohort in the Southeastern United States., Methods: We included HIV-infected patients who initiated care between 1996 and 2012 with a geocodable address and no previous history of HIV clinical care. Patient residence was categorized as urban or rural using United States Department of Agriculture Rural Urban Commuting Area codes. Multivariable linear regression models were fit to estimate the association between patient residence and CD4 cell count at HIV care initiation., Results: Among 1396 patients who met study inclusion criteria, 988 had a geocodable address. Overall, 35% of patients resided in rural areas and presented to HIV care with a mean CD4 cell count of 351 cells/mm (SD, 290). Care initiation mean CD4 cell counts increased from 329 cells/mm (SD, 283) in 1996-2003 to 391 cells/mm (SD, 292) in 2008-2012 (P = 0.006). Rural in comparison with urban patients presented with lower CD4 cell counts with an unadjusted and adjusted mean difference of -48 cells/mm [95% confidence interval, -86 to -10) and -37 cells/mm (95% confidence interval: -73 to -2), respectively, consistently observed across calendar years., Conclusions: HIV care initiation at low CD4 cell counts was common in this Southeastern US cohort and more common among rural area residents.

Objective: Herpesvirus shedding in the oral cavity was analyzed to determine if presence in the oral compartment correlates with systemic changes in HIV-associated immune deficiency as measured by CD4 cell counts, plasma HIV viral load and presence of AIDS-defining events., Design: A5254 is a multicenter, cross-sectional, single-visit study to evaluate oral complications of HIV/AIDS and determine the association between clinical appearance, herpesvirus shedding, and immune status as ascertained by CD4 cell count and HIV viral load. In total, 307 HIV-infected individuals were evaluated and throat wash collected., Methods: Fisher's exact test and Kruskal-Wallis test were used to assess the association between presence of herpesviruses and the state of immunodeficiency as stratified by a combination of CD4 cell count and HIV viral load. Relationship between pathogens and HIV viral load in plasma was modeled by logistic regression., Results: The presence of cytomegalovirus (CMV) and herpes simplex virus-1 in throat wash was associated with decreased CD4 cell counts. By contrast, Kaposi sarcoma-associated herpesvirus and Epstein-Barr virus were similarly detectable across all levels of CD4 cell counts. One unit increase in log10 (HIV viral load) was associated with 1.31 times higher odds of detecting CMV in throat wash when controlling for oral candidiasis, CD4 cell count, and sites (95% confidence interval 1.04-1.65, P = 0.02)., Conclusion: Oral CMV shedding was significantly higher in highly immunocompromised HIV participants. Our finding supports the recommendations to start antiretroviral therapy independent of CD4 cell count as this may have the added benefit to lower the risk of herpesvirus transmission among persons infected with HIV and their partners.

Background: Previous 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., Methods: We 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., Results: Among 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); <100 cells/μL: aIRR = 2.19 (1.44 to 3.33)]. Risk associated with detectable HIV RNA [<400 copies/mL: ref; ≥400 copies/mL: aIRR = 1.36 (1.06 to 1.75)] was significantly increased only when CD4 was excluded., Conclusions: The higher incidence of T1MI in HIV-infected individuals and increased risk associated with lower CD4 count and detectable HIV RNA suggest that early suppressive antiretroviral treatment and aggressive management of traditional CVD risk factors are necessary to maximally reduce MI risk.

Among 149 men who survived Ebola virus disease (EVD) and donated semen 260-1016 days after EVD onset, Ebola virus (EBOV) ribonucleic acid (RNA) was detected in 13 (9%). Of 137 men who donated semen 2 years after EVD onset, 11 (8%) had an EBOV RNA-positive specimen. The mechanism underlying the persistence of EBOV RNA in semen is unclear, and it is unclear whether the detection of viral RNA represents the presence of infectious virus.

Increased scientific attention given to cannabis in the United States has particular relevance for its domestic HIV care population, given that evidence exists for both cannabis as a therapeutic agent and cannabis use disorder (CUD) as a barrier to antiretroviral medication adherence. It is critical to identify relative risk for CUD among demographic subgroups of HIV patients, as this will inform detection and intervention efforts. A Center For AIDS Research Network of Integrated Clinical Systems cohort (N = 10,652) of HIV-positive adults linked to care at seven United State sites was examined for this purpose. Based on a patient-report instrument with validated diagnostic threshold for CUD, the prevalence of recent cannabis use and corresponding conditional probabilities for CUD were calculated for the aggregate sample and demographic subgroups. Generalized estimating equations then tested models directly examining patient demographic indices as predictors of CUD, while controlling for history and geography. Conditional probability of CUD among cannabis-using patients was 49%, with the highest conditional probabilities among demographic subgroups of young adults and those with non-specified sexual orientation (67-69%) and the lowest conditional probability among females and those 50+ years of age (42% apiece). Similarly, youthful age and male gender emerged as robust multivariate model predictors of CUD. In the context of increasingly lenient policies for use of cannabis as a therapeutic agent for chronic conditions like HIV/AIDS, current study findings offer needed direction in terms of specifying targeted patient groups in HIV care on whom resources for enhanced surveillance and intervention efforts will be most impactful.

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

We examined risk factors for advanced hepatic fibrosis [fibrosis-4 (FIB)-4 >3.25] including both current alcohol use and a diagnosis of alcohol use disorder among HIV-infected patients. Of the 12,849 patients in our study, 2133 (17%) reported current hazardous drinking by AUDIT-C, 2321 (18%) had a diagnosis of alcohol use disorder, 2376 (18%) were co-infected with chronic hepatitis C virus (HCV); 596 (5%) had high FIB-4 scores >3.25 as did 364 (15%) of HIV/HCV coinfected patients. In multivariable analysis, HCV (adjusted odds ratio (aOR) 6.3, 95% confidence interval (CI) 5.2-7.5), chronic hepatitis B (aOR 2.0, 95% CI 1.5-2.8), diabetes (aOR 2.3, 95% CI 1.8-2.9), current CD4 <200 cells/mm 3 (aOR 5.4, 95% CI 4.2-6.9) and HIV RNA >500 copies/mL (aOR 1.3, 95% CI 1.0-1.6) were significantly associated with advanced fibrosis. A diagnosis of an alcohol use disorder (aOR 1.9, 95% CI 1.6-2.3) rather than report of current hazardous alcohol use was associated with high FIB-4. However, among HIV/HCV coinfected patients, both current hazardous drinkers (aOR 1.6, 95% CI 1.1-2.4) and current non-drinkers (aOR 1.6, 95% CI 1.2-2.0) were more likely than non-hazardous drinkers to have high FIB-4, with the latter potentially reflecting the impact of sick abstainers. These findings highlight the importance of using a longitudinal measure of alcohol exposure when evaluating the impact of alcohol on liver disease and associated outcomes.

Background: Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals., Methods: In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count., Findings: 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86-1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95-1·22) for threshold 200 and 1·03 (0·96-1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17-3·43) for threshold 200 and 1·24 (0·89-1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (-25·5 to 26·3) cells per μL for threshold 200 and -3·5 (-16·0 to 8·9) cells per μL for threshold 350., Interpretation: Decreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies., Funding: National Institutes of Health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To examine associations between lipohypertrophy and lipoatrophy and illicit drug use, smoking, and at-risk alcohol use among a large diverse cohort of persons living with HIV (PLWH) in clinical care., Methods: 7,931 PLWH at six sites across the United States completed 21,279 clinical assessments, including lipohypertrophy and lipoatrophy, drug/alcohol use, physical activity level, and smoking. Lipohypertrophy and lipoatrophy were measured using the FRAM body morphology instrument and associations were assessed with generalized estimating equations., Results: Lipohypertrophy (33% mild, 4% moderate-to-severe) and lipoatrophy (20% mild, 3% moderate-to-severe) were common. Older age, male sex, and higher current CD4 count were associated with more severe lipohypertrophy (p values <.001-.03). Prior methamphetamine or marijuana use, and prior and current cocaine use, were associated with more severe lipohypertrophy (p values <.001-.009). Older age, detectable viral load, and low current CD4 cell counts were associated with more severe lipoatrophy (p values <.001-.003). In addition, current smoking and marijuana and opiate use were associated with more severe lipoatrophy (p values <.001-.03). Patients with very low physical activity levels had more severe lipohypertrophy and also more severe lipoatrophy than those with all other activity levels (p values <.001). For example, the lipohypertrophy score of those reporting high levels of physical activity was on average 1.6 points lower than those reporting very low levels of physical activity (-1.6, 95% CI: -1.8 to -1.4, p < .001)., Conclusions: We found a high prevalence of lipohypertrophy and lipoatrophy among a nationally distributed cohort of PLWH. While low levels of physical activity were associated with both lipohypertrophy and lipoatrophy, associations with substance use and other clinical characteristics differed between lipohypertrophy and lipoatrophy. These results support the conclusion that lipohypertrophy and lipoatrophy are distinct, and highlight differential associations with specific illicit drug use.

Background: HIV-infected individuals transitioning from incarceration to the community are at risk for loss of viral suppression. We compared the effects of imPACT, a multidimensional intervention to promote care engagement after release, to standard care on sustaining viral suppression after community re-entry., Methods: This trial randomized 405 HIV-infected inmates being released from prisons in Texas and North Carolina with HIV-1 RNA levels <400 copies/mL to imPACT versus standard care. The imPACT arm received motivational interviewing prerelease and postrelease, referral to care within 5 days of release, and a cellphone for medication text reminders. The standard care arm received routine discharge planning and a cellphone for study staff contact. The primary outcome was the difference between arms in week 24 postrelease viral suppression (HIV-1 RNA <50 copies/mL) using intention-to-treat analysis with multiple imputation of missing data., Results: The proportion with 24-week HIV-1 RNA <50 copies/mL was 60% and 61% in the imPACT and standard care arms, respectively [odds ratio for suppression 0.95 (95% confidence interval: 0.59 to 1.53)]. By week 6 postrelease, 86% in the imPACT arm versus 75% in the standard care arm attended at least 1 nonemergency clinic visit (P = 0.02). At week 24, 62% in both arms reported not missing any antiretroviral doses in the past 30 days (P > 0.99)., Conclusions: Higher rates of HIV suppression and medical care engagement than expected based on previous literature were observed among HIV-infected patients with suppressed viremia released from prison. Randomization to a comprehensive intervention to motivate and facilitate HIV care access after prison release did not prevent loss of viral suppression. A better understanding of the factors influencing prison releasees' linkage to community care, medication adherence, and maintenance of viral suppression is needed to inform policy and other strategic approaches to HIV prevention and treatment.

Longitudinal opioid prescription use is unknown among HIV-infected patients. Group-based trajectory modeling followed by multinomial logistic regression was used to identify distinct trajectories and their association with baseline characteristics among 1239 HIV-infected UNC CFAR HIV Clinical Cohort participants, 2000-2014. Three trajectories were identified: (1) 72% never/sporadic opioid use (referent group), (2) 11% episodic use (associated with female sex, depression, drug-related diagnoses, antiretroviral therapy use, and undetectable HIV RNA), and (3) 16% chronic use (associated with older age, female sex, and mental health diagnoses). Overall, opioid prescription decreased substantially with longer time in HIV care among both episodic and chronic users.

Classic determinants of burn mortality are age, burn size, and the presence of inhalation injury. Our objective was to describe temporal trends in patient and burn characteristics, inpatient mortality, and the relationship between these characteristics and inpatient mortality over time. All patients aged 18 years or older and admitted with burn injury, including inhalation injury only, between 2004 and 2013 were included. Adjusted Cox proportional hazards regression models were used to estimate the relationship between admit year and inpatient mortality. A total of 5540 patients were admitted between 2004 and 2013. Significant differences in sex, race/ethnicity, burn mechanisms, TBSA, inhalation injury, and inpatient mortality were observed across calendar years. Patients admitted between 2011 and 2013 were more likely to be women, non-Hispanic Caucasian, with smaller burn size, and less likely to have an inhalation injury, in comparison with patients admitted from 2004 to 2010. After controlling for patient demographics, burn mechanisms, and differential lengths of stay, no calendar year trends in inpatient mortality were detected. However, a significant decrease in inpatient mortality was observed among patients with extensive burns (≥75% TBSA) in more recent calendar years. This large, tertiary care referral burn center has maintained low inpatient mortality rates among burn patients over the past 10 years. While observed decreases in mortality during this time are largely due to changes in patient and burn characteristics, survival among patients with extensive burns has improved.

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

Prior efforts to estimate U.S. prevalence of substance use disorders (SUDs) in HIV care have been undermined by caveats common to single-site trials. The current work reports on a cohort of 10,652 HIV-positive adults linked to care at seven sites, with available patient data including geography, demography, and risk factor indices, and with substance-specific SUDs identified via self-report instruments with validated diagnostic thresholds. Generalized estimating equations also tested patient indices as SUD predictors. Findings were: (1) a 48 % SUD prevalence rate (between-site range of 21-71 %), with 20 % of the sample evidencing polysubstance use disorder; (2) substance-specific SUD rates of 31 % for marijuana, 19 % alcohol, 13 % methamphetamine, 11 % cocaine, and 4 % opiate; and (3) emergence of younger age and male gender as robust SUD predictors. Findings suggest high rates at which SUDs occur among patients at these urban HIV care sites, detail substance-specific SUD rates, and identify at-risk patient subgroups.

Importance: The 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., Objectives: To 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 Participants: This 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 Measures: The 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., Results: Among 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 Relevance: Approximately 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.

Background: It is unclear whether immunosuppression leads to younger ages at cancer diagnosis among people living with human immunodeficiency virus (PLWH). A previous study found that most cancers are not diagnosed at a younger age in people with AIDS, with the exception of anal and lung cancers. This study extends prior work to include all PLWH and examines associations between AIDS, CD4 count, and age at cancer diagnosis., Methods: We compared the median age at cancer diagnosis between PLWH in the North American AIDS Cohort Collaboration on Research and Design and the general population using data from the Surveillance, Epidemiology and End Results Program. We used statistical weights to adjust for population differences. We also compared median age at cancer diagnosis by AIDS status and CD4 count., Results: After adjusting for population differences, younger ages at diagnosis (P < .05) were observed for PLWH compared with the general population for lung (difference in medians = 4 years), anal (difference = 4), oral cavity/pharynx (difference = 2), and kidney cancers (difference = 2) and myeloma (difference = 4). Among PLWH, having an AIDS-defining event was associated with a younger age at myeloma diagnosis (difference = 4; P = .01), and CD4 count <200 cells/µL (vs ≥500) was associated with a younger age at lung cancer diagnosis (difference = 4; P = .006)., Conclusions: Among PLWH, most cancers are not diagnosed at younger ages. However, this study strengthens evidence that lung cancer, anal cancer, and myeloma are diagnosed at modestly younger ages, and also shows younger ages at diagnosis of oral cavity/pharynx and kidney cancers, possibly reflecting accelerated cancer progression, etiologic heterogeneity, or risk factor exposure in PLWH., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: There remains concern regarding the occurrence of noncommunicable diseases (NCDs) among individuals aging with human immunodeficiency virus (HIV), but few studies have described whether disparities between demographic subgroups are present among individuals on antiretroviral therapy (ART) with access to care., Methods: We assessed the first documented occurrence of type 2 diabetes mellitus (DM), chronic kidney disease (CKD), and treated hypertension (HTN) by age, sex, and race within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). HIV-infected adults (≥18 years) who initiated ART were observed for first NCD occurrence between 1 January 2000 and 31 December 2013. Cumulative incidences as of age 70 were estimated accounting for the competing risk of death; Poisson regression was used to compare rates of NCD occurrence by demographic subgroup., Results: We included >50000 persons with >250000 person-years of follow-up. Median follow-up was 4.7 (interquartile range, 2.4–8.1) years. Rates of first occurrence (per 100 person-years) were 1.2 for DM, 0.6 for CKD, and 2.6 for HTN. Relative to non-black women, the cumulative incidences were increased in black women (68% vs 51% for HTN, 52% vs 41% for DM, and 38% vs 35% for CKD; all P < .001); this disparity was also found among men (73% vs 60% for HTN, 44% vs 34% for DM, and 30% vs 25% for CKD; all P < .001)., Conclusions: Racial disparities in the occurrence of DM, CKD, and HTN emphasize the need for prevention and treatment options for these HIV populations receiving care in North America.

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.

Background: Depression 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., Methods: We 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)., Results: The 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., Conclusions: In 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., Competing Interests: The authors have declared that no competing interests exist.

Background: Poor retention in HIV care is associated with worse clinical outcomes and increased HIV transmission. We examined the relationship between self-reported alcohol use, a potentially modifiable behavior, and retention., Methods: A total of 9694 people living with HIV from 7 participating US HIV clinical sites (the Centers for AIDS Research Network of Integrated Clinical Systems) contributed 23,225 observations from January 2011 to June 2014. The retention outcomes were (1) Institute of Medicine (IOM) retention: 2 visits within 1 year at least 90 days apart and (2) visit adherence [proportion of kept visits/(scheduled + kept visits)]. Alcohol use was measured with Alcohol Use Disorders Identification Test-C, generating drinking (never, moderate, and heavy) and binge frequency (never, monthly/less than monthly, weekly/daily) categories. Adjusted multivariable logistic models, accounting for repeat measures, were generated., Results: Of our sample, 82% was men, 46% white, 35% black, and 14% Hispanic. At first assessment, 37% of participants reported never drinking, 38% moderate, and 25% heavy, and 89% of the patients were retained (IOM retention measure). Participants' mean (SD) visit adherence was 84% (25%). Heavy alcohol use was associated with inferior IOM-defined retention (adjusted odds ratio 0.78, 95% confidence interval: 0.69 to 0.88), and daily/weekly binge drinking was associated with lower visit adherence (adjusted odds ratio = 0.90, 95% confidence interval: 0.82 to 0.98)., Conclusions: Both heavy drinking and frequent binge drinking were associated with worse retention in HIV care. Increased identification and treatment of heavy and binge drinking in HIV clinical care settings may improve retention in HIV care, with downstream effects of improved clinical outcomes and decreased HIV transmission., Competing Interests: There are no conflicts of interest to disclose

Background: When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy)., Methods: We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting., Results: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death., Conclusions: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Background: Infections are an important cause of morbidity and mortality after burn injuries. Here, we describe the time line of infections and pathogens after burns., Methods: A retrospective study was performed in a large tertiary care burn center from 2004-2013. Analyses were performed on health care-associated infections (HAIs) meeting Centers for Disease Control and Prevention criteria and on all positive cultures. Incidence rates per 1,000 days were calculated for specific HAI categories and pathogens and across hospitalization time (week 1, weeks 2-3, and week ≥4)., Results: Among 5,524 patients, the median burn size was 4% of total body surface area (interquartile range, 2%-10%). Of the patients, 7% developed an HAI, of whom 33% had >1 HAI episode. Gram-positive bacteria were isolated earlier, and gram-negative bacteria were isolated later during hospitalization. Of 1,788 bacterial isolates, 44% met criteria for multidrug resistance, and 23% met criteria for extensive drug resistance. Bacteria tended to become increasingly resistant to antibiotics as time from admission increased., Conclusions: We observed differences in infection type, pathogen, and antibiotic-resistant bacterium risk across time of hospitalization. These results may guide infection prevention in various stages of the postburn admission., (Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Human 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., Methods: Twelve 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., Results: Among 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., Conclusions: Despite 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., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

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., Methods: We 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., Results: A 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<.001); the rates of most individual OIs decreased as well. During 2008-2010, the leading OIs included Pneumocystis jiroveci pneumonia, esophageal candidiasis, and disseminated Mycobacterium avium complex or Mycobacterium kansasii infection., Conclusions: For HIV-infected persons in care during 2000-2010, rates of first OI were relatively low and generally declined over this time., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)