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To test the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) agonists have beneficial effects on vascular endothelial function, fibrinolysis and inflammation through weight loss-independent mechanisms.Individuals with obesity and prediabetes were randomized to 14 weeks of the GLP-1R agonist liraglutide, hypocaloric diet or the dipeptidyl peptidase-4 inhibitor sitagliptin in a 2:1:1 ratio. Treatment with drug was double blind and placebo-controlled. Measurements were made at baseline, after 2 weeks prior to significant weight loss and after 14 weeks. The primary outcomes were measures of endothelial function: flow-mediated vasodilation (FMD), plasminogen activator inhibitor-1 (PAI-1) and urine albumin-to-creatinine ratio (UACR).Eighty-eight individuals were studied (liraglutide N = 44, diet N = 22, sitagliptin N = 22). Liraglutide and diet reduced weight, insulin resistance and PAI-1, while sitagliptin did not. There was no significant effect of any treatment on endothelial vasodilator function measured by FMD. Post hoc subgroup analyses in individuals with baseline FMD below the median, indicative of greater endothelial dysfunction, showed an improvement in FMD by all three treatments. GLP-1R antagonism with exendin (9-39) increased fasting blood glucose but did not change FMD or PAI-1. There was no effect of treatment on UACR. Finally, liraglutide, but not sitagliptin or diet, reduced the chemokine monocyte chemoattractant protein-1 (MCP-1).Liraglutide and diet reduce weight, insulin resistance and PAI-1. Liraglutide, sitagliptin and diet do not change FMD in obese individuals with prediabetes with normal endothelial function. Liraglutide alone lowers the pro-inflammatory and pro-atherosclerotic chemokine MCP-1, indicating that this beneficial effect is independent of weight loss.

BACKGROUND: Electronic Medical Records (EMR) represent a rich source of data, but the value of EMR for health research relies on accurate ascertainment of clinical diagnoses. Identifying diabetes in EMR is complicated by the variety of accepted diagnostic criteria, some of which can be confounded by conditions such as HIV infection. We compared EMR-based criteria for estimating diabetes prevalence and incidence in the Veterans Administration (VHA), overall and by HIV status, against physician chart review and adjudication. RESEARCH DESIGN AND METHODS: We used laboratory values (serum glucose and hemoglobin A1c% [HbA1c]), ICD-9 codes, and medication records from the United States Veterans Aging Cohort Study Biomarker Cohort (VACS-BC) to identify veterans with any indication of diabetes in the EMR for subsequent physician adjudication. Sensitivity, specificity, PPV, NPV, and kappa statistics were used to evaluate agreement of EMR-based diabetes diagnoses with chart review adjudicated diagnoses. RESULTS: EMR entries were reviewed for 1546 persons with HIV (PWH) and 843 HIV-negative participants through 2015. Agreement was at least moderate overall (kappa ≥0.42) for all pre-specified measures and among PWH vs. HIV-negative, and African-American vs. white subgroups. Having at least one HbA1c ≥6.5% provided substantial agreement with chart adjudication for prevalent and incident diabetes (kappa = 0.89 and 0.73). CONCLUSIONS: Identification of those with diabetes nationally within the VHA can be used in future studies to evaluate treatments, health outcomes, and adjust for diabetes in epidemiologic studies. Our methodology may provide insights for other organizations seeking to use EMR data for accurate determination of diabetes.

Author(s): Bourgi, Kassem; Jenkins, Cathy A; Rebeiro, Peter F; Palella, Frank; Moore, Richard D; Altoff, Keri N; Gill, John; Rabkin, Charles S; Gange, Stephen J; Horberg, Michael A; Margolick, Joseph; Li, Jun; Wong, Cherise; Willig, Amanda; Lima, Viviane D; Crane, Heidi; Thorne, Jennifer; Silverberg, Michael; Kirk, Gregory; Mathews, William C; Sterling, Timothy R; Lake, Jordan; Koethe, John R; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) | Abstract: IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naive PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naive PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with g10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of g10% body weight increase at two years (adjusted odds ration=n1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.

Objectives Adipose tissue affects several aspects of the cellular immune system, but prior epidemiological studies have differed on whether a higher body mass index (BMI) promotes CD4 T-cell recovery on antiretroviral therapy (ART). The objective of this analysis was to assess the relationship between BMI at ART initiation and early changes in CD4 T-cell count. Methods We used the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data set to analyse the relationship between pre-treatment BMI and 12-month CD4 T-cell recovery among adults who started ART between 1998 and 2010 and maintained HIV-1 RNA levels 30 kg/m2). Pretreatment BMI was associated with 12-month CD4 T-cell change (P 30 kg/m2, the observed benefit was attenuated among men to a greater degree than among women, although this difference was not statistically significant. Conclusions A BMI of approximately 30 kg/m2 at ART initiation was associated with greater CD4 T-cell recovery at 12 months compared with higher or lower BMI values, suggesting that body composition may affect peripheral CD4 T-cell recovery.

Objectives Obesity and HIV infection are associated with an increased incidence of noninfectious comorbid medical conditions, but the relationship between body mass index (BMI) and the development of noncommunicable diseases (NCDs) among individuals on antiretroviral therapy (ART) has not been well characterized. Methods A cohort study of adults initiating ART between 1998 and 2010 at an academic centre with systematic laboratory and clinical data collection, including AIDS and NCD diagnoses, was carried out. The relationship between BMI at ART initiation and the risk of incident cardiovascular, hepatic, renal or oncological NCDs was assessed using Cox proportional hazard models. BMI was fitted using restricted cubic splines and models adjusted for age, sex, race, CD4 count, protease inhibitor use, year of initiation, and prior AIDS-defining illness. Results Among 1089 patients in the analysis cohort, 54% had normal BMI, 28% were overweight, and 18% were obese. Baseline BMI was associated with developing an incident NCD (P

Introduction : Long-term survival of HIV patients after initiating highly active antiretroviral therapy (ART) has not been sufficiently described in Latin America and the Caribbean, as compared to other regions. The aim of this study was to describe the incidence of mortality, loss to follow-up (LTFU) and associated risk factors for patients enrolled in the Caribbean, Central and South America Network (CCASAnet). Methods : We assessed time from ART initiation (baseline) to death or LTFU between 2000 and 2014 among ART-naive adults (≥18 years) from sites in seven countries included in CCASAnet: Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru. Kaplan-Meier techniques were used to estimate the probability of mortality over time. Risk factors for death were assessed using Cox regression models stratified by site and adjusted for sex, baseline age, nadir pre-ART CD4 count, calendar year of ART initiation, clinical AIDS at baseline and type of ART regimen. Results : A total of 16,996 ART initiators were followed for a median of 3.5 years (interquartile range (IQR): 1.6–6.2). The median age at ART initiation was 36 years (IQR: 30–44), subjects were predominantly male (63%), median CD4 count was 156 cells/µL (IQR: 60–251) and 26% of subjects had clinical AIDS prior to starting ART. Initial ART regimens were predominantly non-nucleoside reverse transcriptase inhibitor based (86%). The cumulative incidence of LTFU five years after ART initiation was 18.2% (95% confidence interval (CI) 17.5–18.8%). A total of 1582 (9.3%) subjects died; the estimated probability of death one, three and five years after ART initiation was 5.4, 8.3 and 10.3%, respectively. The estimated five-year mortality probability varied substantially across sites, from 3.5 to 14.0%. Risk factors for death were clinical AIDS at baseline (adjusted hazard ratio (HR)=1.65 (95% CI 1.47–1.87); p

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/µL, p< 0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57). 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. To access the supplementary material to this article please see Supplementary Files in the column to the right (under Article Tools). (Published: 18 March 2016) Citation: Cesar C et al. Journal of the International AIDS Society 2016, 19 :20684 http://www.jiasociety.org/index.php/jias/article/view/20684 | http://dx.doi.org/10.7448/IAS.19.1.20684