CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

infarction/stroke/invasive cardiovascular procedure) and DM. Participants were stratified according to their baseline BMI as <20, 20-24.9, 25-29.9 and >30 kg/ m 2 . BMI was lagged by 1 year, and changes from baseline BMI were calculated for each participant, with values carried forward. Poisson regression models were used, adjusted for baseline BMI and key confounders that did not lie on the causal pathway for each outcome, with BMI change fitted as a time varying covariate. Results: We included 43,011 participants with 2,104 CVD and 1,583 DM events over 365,287 and 354,898 person years of follow up (rate:CVD 5.8/1000 (95% confidence interval (CI) 5.5–6.0); DM 4.5/1000 (95% CI 4.2–4.7)). Participants were largely male (74%) with baseline mean age of 40 years and baseline median BMI of 23.0 (IQR: 21.0- 25.3). Risk of CVD by change in BMI from baseline, stratified by baseline BMI strata are shown in Figure 1a with little evidence of an increased risk of CVD with an increased BMI in any baseline BMI strata. Overall there was no statistically significant interaction between baseline BMI strata and BMI change (p=0.16). There was some evidence of an increased rate of CVD with a decrease in BMI of more than 2 kg/m 2 , especially in those with a baseline BMI<20 kg/m 2 . An increase in BMI was associated with an increased risk of DM across all baseline BMI strata (Figure 1b). Conclusion: While increases in BMI across all levels of baseline BMI were not associated with an increased risk of CVD, such changes were consistently associated with increased risk of DM. There was also some evidence of an increased risk of CVD with a decrease in BMI. The extent to which these results apply to HIV-positive people with increased weight while receiving contemporary ARVs are uncertain.

cell phenotypes were compared between the losartan and placebo arms using linear mixed models. Results: One hundred and eight participants were randomized (n=52 to losartan; n=56 to placebo); 97% had a month 12 visit and 99% of expected visits were completed overall. Median age was 57 years, baseline and nadir CD4+ count were 408 and 120 cells/mm 3 ; 96%were male, 56%white, 20% current smokers, 26% taking lipid-lowering medication, and 49% taking an integrase strand transfer inhibitor. The table reports baseline levels of blood inflammation and immune measures, as well as the treatment effect of losartan versus placebo. Losartan treatment was not associated with an improvement in any of these measures, nor with CD8+ T-cell memory subsets and activation (data not shown). Losartan reduced systolic and diastolic blood pressure by 6 and 5mmHg, respectively, and raised serum creatinine by 0.05mg/dL (p<0.01 for all). Losartan was not associated with more serious adverse events. Conclusion: Among older persons with HIV and viral suppression, losartan did not improve blood measures of inflammation, immune activation, fibrotic activity, nor T-cell immune recovery. Losartan treatment is unlikely to reduce inflammation associated co-morbidities among persons with HIV infection to a clinically meaningful degree, beyond the established benefits from lowering blood pressure

Oral Abstracts

85 EFFECTS OF HIV INFECTION AND IMMUNE REGULATION ON LONGITUDINAL LUNG FUNCTION DECLINE

Jing Sun 1 , Jacquie Astemborski 1 , Sarath Raju 2 , M. Brad Drummond 3 , Robert H. Brown 2 , Shruti H. Mehta 1 , Richard D. Moore 2 , Meredith C. McCormack 2 , Gregory D. Kirk 1 , for the Study of HIV Infection in the Etiology of Lung Disease (SHIELD) cohort 1 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 3 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: People living with HIV (PWH) have higher prevalence of lung function abnormalities compared to demographically and behaviorally similar people without HIV (HIV-). However, high quality longitudinal data describing the impact of HIV and of immune dysregulation on lung function decline over prolonged observation by age remains limited. Methods: Data from the Study of HIV Infection in the Etiology of Lung Disease (SHIELD) cohort was used to evaluate the role of HIV and aging on lung function decline. Pre-bronchodilator FEV1 was repeatedly measured by spirometry at semiannual visits from 2009 to 2017 using ATS standards. HIV serostatus, HIV RNA, CD4 and CD8 counts were measured either in study or routine clinical visits. Time-varying CD4 nadir was defined as lowest CD4 observed up until each visit. Linear regression with generalized estimating equations, adjusted for age at entry, race, gender, current smoking status, and life-time pack-years, was used to evaluate longitudinal change in annualized FEV1 by HIV serostatus, CD4:CD8, and CD4 nadir. Results: Of 1156 HIV+ and 1168 HIV- participants with 8341 person-years of follow-up, median age at entry was 50 years, 85%were black, 65%male, 79% current smokers, median cigarette exposure was 19 pack-years, and median % predicted FEV1 was 90%. Among PWH, 38% had CD4 <200, 59% had detectable HIV RNA, 78% had CD4:CD8≤0.8. At entry, PWH had 133 ml lower FEV1 compared to HIV- (p<0.01). FEV1 declined significantly faster among PWH before age of 50, but declined at similar rate after age of 50

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LOSARTAN TO REDUCE INFLAMMATION AND FIBROSIS ENDPOINTS IN HIV DISEASE (LIFE-HIV) Jason V. Baker 1 , Julian Wolfson 2 , Gary Collins 2 , Caryn G. Morse 3 , Frank S. Rhame 4 , Andelike Liappis 5 , Stacey Rizza 6 , Zelalem Temesgen 6 , Charalampos Mystakelis 3 , Steven G. Deeks 7 , James Neaton 2 , Timothy Schacker 2 , Irini Sereti 3 , Russell Tracy 8 1 Hennepin Healthcare Research Institute, Minneapolis, MN, USA, 2 University of Minnesota, Minneapolis, MN, USA, 3 NIAID, Bethesda, MD, USA, 4 Allina Health, Minneapolis, MN, USA, 5 Washington DC VA Medical Center, Washington, DC, USA, 6 Mayo Clinic, Rochester, MN, USA, 7 University of California San Francisco, San Francisco, CA, USA, 8 University of Vermont, Burlington, VT, USA Background: Persistent inflammation and incomplete immune recovery among persons with HIV are associated with increased disease risk. Angiotensin receptor blockers (ARB) have been shown to down-regulate inflammation and fibrosis, in part, via inhibition of NFkB and TGFb pathways, respectively. We hypothesized that the ARB losartan would reduce inflammation, inhibit fibrosis, and concurrently improve immune recovery. Methods: Treatment effects of oral losartan (100mg) versus placebo were investigated in a randomized (1:1), double-blind, placebo-controlled trial, among persons with HIV of age ≥50 years, receiving ART, with plasma HIV RNA <200 copies/mL and a CD4+ count ≤600 cells/mL. Blood was collected at baseline and months 1, 3, 6, 9, and 12. Inflammation and fibrosis biomarkers (Table) were measured using ELISA, electrochemiluminescence, and immunoturbidimetric methods, and T-cell and monocyte phenotypes were assessed with flow cytometry among a subset of participants. Baseline-to- 12-month changes in (log-2 transformed) biomarkers and (untransformed)

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CROI 2020