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Purpose: Despite effective antiretroviral therapy, rates of end‐stage liver disease (ESLD) remain high. It is not clear whether contemporary antiretrovirals contribute to the risk of ESLD. Methods: We included patients from cohorts with validated ESLD data in the North American AIDS Cohort Collaboration on Research and Design. Patients had to initiate antiretroviral therapy after 1 January 2004 with a nucleos(t)ide backbone of either abacavir/lamivudine or tenofovir/emtricitabine and a contemporary third (anchor) drug. Patients were followed until a first ESLD event, death, end of a cohort's ESLD validation period, loss to follow‐up or 31 December 2015. We estimated associations between cumulative exposure to each drug and ESLD using a hierarchical Bayesian survival model with weakly informative prior distributions. Results: Among 10 564 patients included from 12 cohorts, 62 had an ESLD event. Of the nine anchor drugs, boosted protease inhibitors atazanavir and darunavir had the strongest signals for ESLD, with increasing hazard ratios (HR) and narrowing credible intervals (CrI), from a prior HR of 1.5 (95% CrI 0.32–7.1) per 5 year's exposure to posterior HRs respectively of 1.8 (95% CrI 0.82–3.9) and 2.0 (95% CrI 0.86–4.7). Both backbones and efavirenz showed no signal. Hepatitis C coinfection was the most important covariate risk factor (HR 4.4, 95% CrI 2.6–7.0). Conclusions: While contemporary antiretrovirals pose less risk for ESLD than hepatitis coinfection, atazanavir and darunavir had a toxicity signal. We show how hierarchical Bayesian modelling can be used to detect toxicity signals in cohort event monitoring data even with complex treatments and few events. [ABSTRACT FROM AUTHOR]

Introduction In 2012, the World Health Organization (WHO) estimated there were 1.3 million HIV-positive individuals in the United States and Canada and 1.5 million in the countries of Latin America [...], Introduction: Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. Methods: HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. Results: The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/mL, p Conclusions: HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation. Keywords: HIV; antiretroviral therapy; highly active; mortality; Latin America; North America; cohort studies.

Objective: The aim of this study was to describe the association of individual- level characteristics (sex, race/ethnicity, birth weight, maternal education) with child BMI within each US Census region and variation in child BMI by region. Methods: This study used pooled data from 25 prospective cohort studies. Region of residence (Northeast, Midwest, South, West) was based on residential zip codes. Age- and sex- specific BMI z scores were the outcome. Results: The final sample included 14,313 children with 85,428 BMI measurements, 49% female and 51% non- Hispanic White. Males had a lower average BMI z score compared with females in the Midwest (β = -0.12, 95% CI: -0.19 to -0.05) and West (β = -0.12, 95% CI: -0.20 to -0.04). Compared with non- Hispanic White children, BMI z score was generally higher among children who were Hispanic and Black but not across all regions. Compared with the Northeast, average BMI z score was significantly higher in the Midwest (β = 0.09, 95% CI: 0.05 to 0.14) and lower in the South (β = -0.12, 95% CI: -0.16 to -0.08) and West (β = -0.14, 95% CI: -0.19 to -0.09) after adjustment for age, sex, race/ethnicity, and birth weight. Conclusions: Region of residence was associated with child BMI z scores, even after adjustment for sociodemographic characteristics. Understanding regional influences can inform targeted efforts to mitigate BMI- related disparities among children. [ABSTRACT FROM AUTHOR]

Background Integrase strand transfer inhibitor (INSTI)–based combination antiretroviral therapy (cART) is associated with greater weight gain among persons with human immunodeficiency virus (HIV), though metabolic consequences, such as diabetes mellitus (DM), are unclear. We examined the impact of initial cART regimen and weight on incident DM in a large North American HIV cohort (NA-ACCORD). Methods cART-naive adults (≥18 years) initiating INSTI-, protease inhibitor (PI)–, or nonnucleoside reverse transcriptase inhibitor (NNRTI)–based regimens from January 2007 through December 2017 who had weight measured 12 (±6) months after treatment initiation contributed time until clinical DM, virologic failure, cART regimen switch, administrative close, death, or loss to follow-up. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DM by cART class. Mediation analyses, with 12-month weight as mediator, similarly adjusted for all covariates. Results Among 22 884 eligible individuals, 47% started NNRTI-, 30% PI-, and 23% INSTI-based cART with median follow-up of 3.0, 2.3, and 1.6 years, respectively. Overall, 722 (3%) developed DM. Persons starting INSTIs vs NNRTIs had incident DM risk (HR, 1.17 [95% CI,.92–1.48]), similar to PI vs NNRTI initiators (HR, 1.27 [95% CI, 1.07–1.51]). This effect was most pronounced for raltegravir (HR, 1.42 [95% CI, 1.06–1.91]) vs NNRTI initiators. The INSTI–DM association was attenuated (HR, 1.03 [95% CI,.71–1.49] vs NNRTIs) when accounting for 12-month weight. Conclusions Initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of DM, likely mediated through weight gain. [ABSTRACT FROM AUTHOR]

From 2005 to 2018, among 32013 adults with human immunodeficiency virus entering care, median time to antiretroviral therapy (ART) prescription declined from 69 to 6 days, CD4 count at entry into care increased from 300 to 362 cells/μL, and CD4 count at ART prescription increased from 160 to 364 cells/μL. [ABSTRACT FROM AUTHOR]

Abstract We assessed CD4 count at initial presentation for HIV care among ≥50-year-olds from 1997-2007 in 13 US and Canadian clinical cohorts and compared to 3) and 95% confidence intervals ([,]) were determined using linear regression stratified by age category and adjusted for gender, race/ethnicity, HIV transmission risk and cohort. From 1997-2007, the proportion of individuals presenting for HIV care who were ≥50-years-old increased from 17% to 27% (p-value < 0.01). The median CD4 count among ≥50 year-olds was consistently lower than younger adults. The interaction of age group and calendar year was significant (p-value 3; ≥50-year-olds: 7 [5 , 9] cells/mm3), after adjusting for sex, race/ethnicity, HIV transmission risk group and cohort; however, increases in the two groups were similar after 2000. A greater proportion of older individuals had an AIDS-defining diagnosis at, or within three months prior to, first presentation for HIV care compared to younger individuals (13% vs. 10%, respectively). Due to the increasing proportion, consistently lower CD4 counts, and more advanced HIV disease in adults ≥50-year-old at first presentation for HIV care, renewed HIV testing efforts are needed.

Background: Improved access to effective antiretroviral therapy has meant that people living with HIV (PLHIV) are surviving to older ages. However, PLHIV may be ageing differently to HIV-negative individuals, with dissimilar burdens of non-communicable diseases, such as hypertension. While some observational studies have reported a higher risk of prevalent hypertension among PLHIV compared to HIV-negative individuals, others have found a reduced burden. To clarify the relationship between HIV and hypertension, we identified observational studies and pooled their results to assess whether there is a difference in hypertension risk by HIV status. Methods: We performed a global systematic review and meta-analysis of published cross-sectional studies that examined hypertension risk by HIV status among adults aged > 15 (PROSPERO: CRD42019151359). We searched MEDLINE, EMBASE, Global Health and Cochrane CENTRAL to August 23, 2020, and checked reference lists of included articles. Our main outcome was the risk ratio for prevalent hypertension in PLHIV compared to HIV-negative individuals. Summary estimates were pooled with a random effects model and meta-regression explored whether any difference was associated with study-level factors. Results: Of 21,527 identified studies, 59 were eligible (11,101,581 participants). Crude global hypertension risk was lower among PLHIV than HIV-negative individuals (risk ratio 0.90, 95% CI 0.85–0.96), although heterogeneity between studies was high (I2 = 97%, p < 0.0001). The relationship varied by continent, with risk higher among PLHIV in North America (1.12, 1.02–1.23) and lower among PLHIV in Africa (0.75, 0.68–0.83) and Asia (0.77, 0.63–0.95). Meta-regression revealed strong evidence of a difference in risk ratios when comparing North American and European studies to African ones (North America 1.45, 1.21–1.74; Europe 1.20, 1.03–1.40). Conclusions: Our findings suggest that the relationship between HIV status and prevalent hypertension differs by region. The results highlight the need to tailor hypertension prevention and care to local contexts and underscore the importance of rapidly optimising integration of services for HIV and hypertension in the worst affected regions. The role of different risk factors for hypertension in driving context-specific trends remains unclear, so development of further cohorts of PLHIV and HIV-negative controls focused on this would also be valuable. [ABSTRACT FROM AUTHOR]

Introduction: The third of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90‐90‐90 targets is to achieve a 90% rate of viral suppression (HIV viral load <1000 HIV‐1 RNA copies/ml) in patients on antiretroviral treatment (ART) by 2020. However, some countries use different thresholds when reporting viral suppression, and there is thus a need for an adjustment to standardize estimates to the <1000 threshold. We aim to propose such an adjustment, to support consistent monitoring of progress towards the "third 90" target. Methods: We considered three possible distributions for viral loads in ART patients: Weibull, Pareto and reverse Weibull (imposing an upper limit but no lower limit on the log scale). The models were fitted to data on viral load distributions in ART patients in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration (representing seven global regions) and the ART Cohort Collaboration (representing Europe), using separate random effects models for adults and children. The models were validated using data from the World Health Organization (WHO) HIV drug resistance report and the Brazilian national ART programme. Results: Models were calibrated using 921,157 adult and 37,431 paediatric viral load measurements, over 2010–2019. The Pareto and reverse Weibull models provided the best fits to the data, but for all models, the "shape" parameters for the viral load distributions differed significantly between regions. The Weibull model performed best in the validation against the WHO drug resistance survey data, while the Pareto model produced uncertainty ranges that were too narrow, relative to the validation data. Based on these analyses, we recommend using the reverse Weibull model. For example, if a country reports an 80% rate of viral suppression at <200 copies/ml, this model estimates the proportion virally suppressed at <1000 copies/ml is 88.3% (0.800.56), with uncertainty range 85.5–90.6% (0.800.70–0.800.44). Conclusions: Estimates of viral suppression can change substantially depending on the threshold used in defining viral suppression. It is, therefore, important that viral suppression rates are standardized to the same threshold for the purpose of assessing progress towards UNAIDS targets. We have proposed a simple adjustment that allows this, and this has been incorporated into UNAIDS modelling software. [ABSTRACT FROM AUTHOR]

Background: Persons with HIV (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk.Methods: In six US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005-2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (Years 2-5) and long-term (Years 6-11) suppression and lowest pre-suppression CD4 count <200 and ≥200 cells/µL, Poisson regression models estimated hospitalization incidence rate ratios (aIRR) comparing patients by time-updated CD4 count category, adjusted for cohort, age, gender, calendar year, suppression duration, and lowest pre-suppression CD4 count.Results: The 6997 included patients (19 980 person-years) were 81% cisgender men and 40% White. Among patients with lowest pre-suppression CD4 <200 cells/μL (44%), patients with current CD4 200-350 versus >500 cells/μL had an aIRR of 1.44 during early suppression (95% CI 1.01-2.06), and 1.67 (1.03-2.72) during long-term suppression. Among patients with lowest pre-suppression CD4 ≥200 (56%), patients with current CD4 351-500 versus >500 cells/μL had an aIRR of 1.22 (0.93-1.60) during early suppression and 2.09 (1.18-3.70) during long-term suppression.Conclusions: Virologically suppressed patients with lower CD4 counts experienced higher hospitalization rates, and could potentially benefit from targeted clinical management strategies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART). Methods We evaluated AIDS-free, ART-naive PLWH during 1996–2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350–500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject's age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses. Results Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI],.37–.86), AIDS-defining cancers (HR 0.23; 95% CI,.11–.49), any virus-related cancer (HR 0.30; 95% CI,.16–.54), Kaposi sarcoma (HR 0.25; 95% CI,.10–.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI,.06–.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference −1.6; 95% CI, −2.8, −.5). Conclusions Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology. [ABSTRACT FROM AUTHOR]

Seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies was 10% among the subset of decedents undergoing forensic postmortem examination in June in Maryland. Decedents of motor vehicle crashes had similar seroprevalence compared with those with a natural death (including decedents with SARS-CoV-2 infection). Decedents of motor vehicle crashes may be a sentinel surveillance population. [ABSTRACT FROM AUTHOR]

With increasing effectiveness of antiretroviral therapy, people with HIV (PWH) are living longer and the prevalence of older PWH continues to increase. Accordingly, PWH are experiencing an increased burden of age-related comorbidities. With this shifting demographics, clinicians and researchers face additional challenges in how to identify, address, and manage the complex intersections of HIV- and aging-related conditions. Established in 2009, the International Workshop on HIV and Aging brings together clinicians and researchers in cross-disciplinary fields along with community advocates and PWH to address the multidisciplinary nature of HIV and aging. This article summarizes plenary talks from the 10th Annual International Workshop on HIV and Aging, which took place in New York City on October 10 and 11, 2019. Presentation topics included the following: the burdens of HIV-associated comorbidities, aging phenotypes, community engagement, and loneliness; these issues are especially important for older PWH, considering the current COVID-19 pandemic. We also discuss broad questions and potential directions for future research necessary to better understand the interaction between HIV and aging. [ABSTRACT FROM AUTHOR]

Increasing diverse engagement in the Society for Epidemiologic Research (SER) will positively impact the field of epidemiology. As the largest and longest-running epidemiologic society in North America, SER has long been a pioneer in promoting diversity and inclusion. A recent survey of SER members, however, showed there is still room for improving diversity, inclusion, representation, and participation in the Society. In this commentary, as members of both the SER and the Johns Hopkins Bloomberg School of Public Health Department of Epidemiology's Inclusion, Diversity, Equity, Anti-Racism, and Science (Epi IDEAS) Working Group, we recommend 4 goals for the SER Annual Meeting and beyond: 1) convene epidemiologic researchers with diverse backgrounds and ideas; 2) promote an inclusive environment at the SER Annual Meeting; 3) develop, compile, and disseminate best practices to honor diversity in epidemiologic research; and 4) increase prioritization of health disparities research and methods. We also suggest strategies for achieving these goals so that SER can better include, support, and elevate members from historically disadvantaged groups. While our recommendations are tailored specifically to SER, the greater epidemiologic and academic communities could benefit from adopting these goals and strategies within their professional societies and conferences. [ABSTRACT FROM AUTHOR]