CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: Among US veterans with HIV, depression is associated with a significant increase in the incidence of DM. Future research should examine whether depression treatment lowers diabetes risk in PLWH.

evaluated longitudinal relationships between hyperglycemia and objective measures of physical function in men with and without HIV. Methods: The Multicenter AIDS Cohort Study (MACS) is a prospective study of men with or at risk for HIV. MACS participants undergo semi-annual assessments, including measures of glycemic status (fasting blood glucose and hemoglobin A1C (HbA1C)), grip strength and gait speed. Glycemic status was categorized as normal, impaired fasting glucose (IFG), controlled diabetes mellitus ((DM) (HbA1C <7.5%)) or uncontrolled DM (HbA1C >7.5%). Linear mixed models with random intercept were used to assess associations between glycemic status, gait speed and grip strength between 2006-2018. Results: Of 2,575 men, 54%were PWH. Mean age at baseline was 45.0 years among PWH and 49.2 years among men without HIV. At baseline, DM was more common among men with vs without HIV (p <0.05) and PWH had slower gait speed (p=0.001) but not reduced grip strength compared to seronegative controls. In multivariate models including all participants, HIV serostatus was not significantly associated with change in gait speed or grip strength (all p>0.05). Compared to men with normal glucose, those with controlled DM had greater gait speed decline (-0.015 m/s [-0.028, -0.001], p=0.03) and those with uncontrolled diabetes had greater grip strength decline (-0.877 kg [-1.623, -0.130], p=0.021) regardless of serostatus. In multivariate models restricted to PWH, neither IFG nor DM had significant effects on gait speed, but uncontrolled DMwas associated with significantly greater decline in grip strength (-1.818 kg [-2.868, -0.767]; p=0.001), with a larger effect among men with HIV vs all participants (-1.818 vs -0.877 kg). Conclusion: Abnormal glucose metabolismwas associated with declines in gait speed and grip strength regardless of HIV serostatus, with uncontrolled DM exerting a greater effect on grip strength decline among PWH. These data suggest that improved glucose control, independent of virologic suppression, is an intervenable target to prevent progression of physical function limitations among PWH. 684 GREATER INCIDENCE OF DIABETES OVER 10 YEARS AMONG DEPRESSED US VETERANS WITH HIV Kassem Bourgi 1 , Suman Kundu 2 , Jesse C. Stewart 1 , Matthew Freiberg 2 , Samir K. Gupta 1 1 Indiana University, Indianapolis, IN, USA, 2 Vanderbilt University, Nashville, TN, USA Background: Persons living with HIV (PLWH) have an increased prevalence of depression and incidence of cardiovascular disease (CVD) and diabetes mellitus (DM). We previously found that depressed US veterans with HIV have a greater incidence of CVD, possibly due to biological (increased systemic inflammation/ coagulation) and/or behavioral (smoking, sedentary lifestyle, insomnia, poor medication adherence) mechanisms. As these mechanisms may also predispose to DM, we evaluated whether baseline depressive symptom severity predicts incident DM in US veterans living with HIV. Methods: We used the Veterans Aging Cohort Study (VACS)-Survey Cohort and included patients without DM at baseline. Baseline DM was identified by a validated measure consisting of ICD-9 codes, laboratory tests, and DM medications. Baseline depressive symptom severity was assessed using the Patient Health Questionnaire-9 (PHQ-9), with prevalent depression defined by a score ≥10. Participants were followed until incident DM, death, or last follow-up date (12/31/14). Incident DM cases were identified by ICD-9 codes. Multivariate Cox regression models were run to examine the associations between baseline PHQ-9 variables (continuous and categorical) and incident DM. Results: 2,936 PLWH were included, 628 (21%) of whom had prevalent depression. The median follow-up time was 9.6 years, and a total of 466 (15.8%) incident diabetes cases were identified. The unadjusted incidence rate of DM per 100 person-year was 21.4 (95% CI: 17.5-25.8) in depressed veterans vs 18.9 (95% CI: 17.0-20.9) in nondepressed veterans. Cox models revealed that each 1-SD increase in PHQ-9 score (5.6 points of a 0-27 scale) was associated with a 12% (HR=1.12, 95% CI: 1.02-1.22, p=0.015) and 10% (HR=1.10, 95% CI: 1.00-1.20, p=0.048) increase in the risk of incident diabetes after adjustment for demographics alone and demographics plus traditional DM risk factors, respectively. Similarly, compared to nondepressed veterans, depressed veterans (PHQ-9 score≥10) had a 24% (HR=1.24, 95% CI: 1.00-1.55, p=0.050) and 18% (HR=1.18, 95% CI: 0.94-1.47, p=0.148) greater risk of incident diabetes after adjustment for demographics alone and demographics plus traditional DM risk factors, respectively.

685 TRICARBOXYLIC ACID METABOLITES PREDICT METABOLIC COMORBIDITIES AND DEATH IN AGING PWH

Corrilynn O. Hileman 1 , Sausan Azzam 2 , Daniela Schlatzer 2 , Kunling Wu 3 , Katherine Tassiopoulos 3 , Roger Bedimo 4 , Ronald J. Ellis 5 , Kristine M. Erlandson 6 , Susan L. Koletar 7 , Alan Landay 8 , Frank J. Palella 9 , Muralidhar Pallaki 10 , Babafemi Taiwo 9 , Charles L. Hoppel 2 , Robert Kalayjian 1 1 MetroHealth Medical Center, Cleveland, OH, USA, 2 Case Western Reserve University, Cleveland, OH, USA, 3 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 4 VA North Texas Health Care Center, Dallas, TX, USA, 5 University of California San Diego, San Diego, CA, USA, 6 University of Colorado Denver, Denver, CO, USA, 7 The Ohio State University, Columbus, OH, USA, 8 Rush University, Chicago, IL, USA, 9 Northwestern University, Chicago, IL, USA, 10 Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA Background: Monocyte activation is implicated in the pathogenesis of age-associated comorbidities in people with HIV (PWH). Upon activation, macrophages switch or remodel their metabolism from predominantly oxidative phosphorylation to glycolysis resulting in accumulation of the tricarboxylic acid (TCA) metabolites, succinate, and citrate. These metabolites engage diverse cellular pro-inflammatory pathways that may contribute to comorbidity. Methods: Associations between entry fasting plasma succinate and citrate concentrations, quantified by liquid chromatography mass spectrometry, and incident comorbidities were analyzed by proportional hazard models from a random sample of participants in the prospective, multicenter AIDS Clinical Trials Group HIV Infection, Aging, and Immune Function Long-Term Observational (HAILO) study. Clinically relevant variables, age, sex, race/ ethnicity, and smoking, were evaluated as confounders by adding them one at a time to univariate models. Results: 376 participants were included. Median age was 51 (range 40-77) years, 81%were male and 53%were black or Hispanic. Median BMI was 27 (interquartile range or IQR 24-30) kg/m 2 and 60%were current or former smokers. Median entry and nadir CD4+ cell counts were 613 (IQR 449-825) and 203 (IQR 68-317) cells/mm 3 , respectively, and 93% had HIV-1 RNA levels <50 copies/ml with 7.7 (IQR 4.3-11.8) median years of prior antiretroviral therapy. The median follow-up duration was 240 weeks. Higher succinate concentrations were associated with an increased hazard of hypertension; higher citrate concentrations were associated with each of the following: the composite endpoint of cardiovascular disease (CVD) or death, diabetes, and death due to all causes (see Table for estimates). Age attenuated the associations with hypertension and CVD or death; including other covariates did not change the results. Conclusion: These associations implicate metabolic remodeling in the pathogenesis of age-associated comorbidities among PWH.

Poster Abstracts

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CROI 2020 250