CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

increasing age in persons with HIV, though few women have been studied. We examined the effects of age, sex, and HIV serostatus on muscle density to understand potential mechanisms of impaired physical function. Methods: Men and women with and without HIV in the musculoskeletal substudies of the Multicenter AIDS Cohort Study (BOSS) and Women’s Interagency HIV Study (MSK) were included. Participants underwent L4-L5 computed tomography scans to quantify total density (Hounsfield Units, HU) and area (centimeters2) of four trunk muscle groups. We identified factors associated with muscle density and area using generalized linear regression models. Results: 387 men (198 HIV) and 184 women (118 HIV) had available CT scans. Among men, mean age was 64, 20%were black, 13% current smokers, and 19%were obese (BMI ≥30 kg/m 2 ). Among women, mean age was 50, 51% were black, 53% current smokers, and 44%were obese. All with HIV were on ART. Older age, female sex, and obesity were associated with lower muscle density in all 4 muscle groups; HIV serostatus was associated only with lower psoas density (table). Black race was associated with greater muscle density of nearly all muscle groups. No interaction between sex and HIV serostatus was observed. In sex-stratified models, HIV infection was significantly associated with lower psoas density in men (-1.8 [SE 0.54]HU, p=0.01) but not women (-1.0 [0.8]HU, p=0.19). Muscle area was lower with older age (effect range:-0.22 to -0.6 cm 2 ) and female sex (-6.0 to -3.1), but greater with obesity (range:1.5 to 5.4), all p≤0.02; no race effect was detected. HIV serostatus was associated with greater lateralis (1.0 [0.4],p=0.02) and paraspinal (0.8[0.4],p=0.03) but lower psoas (-0.6[0.2], p=0.01) area. Similar to density, in sex-stratified models, the association between HIV serostatus and area was only in men. Conclusion: Older age and being a woman was associated with smaller and fattier muscle, while obesity was associated with larger and fattier muscle. Detrimental effects of HIV on the psoas density and area, particularly among men, may have important implications on balance, trunk stability, and mobility. 706 CONSISTENT STATIN USE DOES NOT AFFECT AGE-ASSOCIATED GAIT SPEED AND STRENGTH DECLINES Kristine M. Erlandson 1 , Susan Langan 2 , Jing Sun 2 , Jordan E. Lake 3 , Frank J. Palella 4 , Lawrence Kingsley 5 , Todd T. Brown 6 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3 University of Texas at Houston, Houston, TX, USA, 4 Northwestern University, Chicago, IL, USA, 5 University of Pittsburgh, Pittsburgh, PA, USA, 6 Johns Hopkins University, Baltimore, MD, USA Background: Statin use decreases inflammation and reduces cardiovascular events, and may be useful among persons with HIV, who have increased risk of cardiovascular (CV) events. Other benefits are unclear; some studies suggest that statins benefit physical function despite myalgias as a common side effect. We compared age-associated changes in physical function among men with or without statin use in the Multicenter AIDS Cohort Study. Methods: Men 40-75 years old with ≥2 measures of gait speed or grip strength (baseline=2007) were included. Consistent statin use was defined as use at ≥80% of visits. Gait speed was measured on a 4-m course and grip strength by handheld dynamometer. Generalized estimating equations included an interaction term for statin group and age; models were further adjusted for demographics, HIV status, and CV risk factors. Results: Among 2021 men, median age was 52 (IQR 46,58) years; 68%were white, 27% black non-Hispanic, and 60%were overweight/obese. 636 were consistent (51%with HIV), 398 intermittent (61% HIV), and 987 never statin users (49% HIV). Duration of follow-up was 8.5 years (IQR 4.4, 10.4). Baseline gait speed was 1.12 m/sec (IQR 0.99, 1.25) and grip strength 38 kg (IQR 32, 44). Unadjusted changes in gait and grip are shown in the Figure. After adjusting for baseline, demographics, and CV risk factors, gait speed declined at -0.0028 m/s per year of age among all men, with no significant difference in gait speed decline among consistent vs never users (-0.0002 [-0.002, 0.0016], p=0.87). Intermittent users had a steeper gait speed decline over time vs never users (-0.0028 [-0.0048, -0.0007], p=0.007). Similar effects were seen with statin group and grip strength, with similar strength changes over time among

704 EXERCISE-INDUCED EPIGENETIC CHANGES IN MUSCLE DIFFER BY HIV SEROSTATUS Kristine M. Erlandson 1 , Colleen Julian 1 , Iain Konigsberg 1 , Jing Sun 2 , Todd T. Brown 3 , Catherine M. Jankowski 1 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3 Johns Hopkins Hospital, Baltimore, MD, USA Background: Exercise is an effective intervention for improving physical function among aging persons. Whether persons with HIV (PWH) experience the same benefits of exercise, and whether mechanisms underlying exercise effects are unique to HIV is not well understood. Methods: Sedentary PWH (16 baseline; 14 paired) and controls (18 baseline; 15 paired), all men, aged 50 to 75 underwent biopsy of the vastus lateralis prior to and following 24 weeks of supervised cardiovascular and resistance exercise training. Skeletal muscle DNA methylation was quantified on MethylationEPIC BeadChip 850K array (Illumina), normalized and adjusted for batch effects. Linear models were fit for methylation values to test for the association of HIV status or exercise, adjusted for age and race/ethnicity to generate differentially methylated positions (DMPs). DMPs were then used to identify differentially methylated regions (DMRs) between pre- and post-exercise intervention for PWH and controls using Comb-p and adjusted for multiple comparisons. Pathway analysis was performed using Ingenuity. Results: Pre-exercise, 983 DMPs differed between PWH and controls. Top canonical pathways included gas signaling (p=3.5E-3), IL-1 signaling (p=6.9E-3) and androgen signaling (p=1.3E-2). Post-exercise, 237 DMPs differed between PWH and controls, enriching neuroinflammation signaling (p=5.0E-3) and interferon pathways (p=1.6E-2). Exercise induced 209 genome-wide significant DMRs in PWH; top enriched canonical pathways included amytrophic lateral sclerosis signaling (p=1.3E-6), glutamate receptor signaling (p=1.1E-3), phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling (p=3.7E-3), glial-cell-line-derived neurotrophic factor family ligand-receptor interactions (p=3.6E-3), and fibroblast growth factor signaling (p=5.1E-3). In controls, exercise training induced 75 genome-wide significant DMRs, enriching pathways associated with cyclins and cell cycle regulation (p=1.6E-3), telomerase signaling (p=3.4E-3), alanine degradation/biosynthesis (p=5.7xE- 3), and hippo signaling (p=1.8E-3). Conclusion: Epigenetic responses to exercise differed by serostatus: PWH experienced changes in DNA methylation status of genes involved in oxidative damage, mitochondrial function, angiogenesis, and metabolismwhile controls experienced changes in cell cycle, proliferation, protein synthesis and immune senescence. 705 EFFECTS OF HIV, AGE, AND SEX ON SKELETAL MUSCLE MASS AND DENSITY Kristine M. Erlandson 1 , Susan Langan 2 , Jing Sun 2 , Jordan E. Lake 3 , Anjali Sharma 4 , Stefan Adrian 1 , Ann Scherzinger 1 , Frank J. Palella 5 , Lawrence Kingsley 6 , Stephen J. Gange 7 , Phyllis Tien 8 , Michael T.Yin 9 , Todd T. Brown 7 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3 University of Texas at Houston, Houston, TX, USA, 4 Albert Einstein College of Medicine, Bronx, NY, USA, 5 Northwestern University, Chicago, IL, USA, 6 University of Pittsburgh, Pittsburgh, PA, USA, 7 Johns Hopkins University, Baltimore, MD, USA, 8 University of California San Francisco, San Francisco, CA, USA, 9 Columbia University Medical Center, New York, NY, USA Background: Lower muscle density due to ectopic fat in skeletal muscle is associated with worse physical function. Muscle density declines with antiretroviral therapy (ART) initiation; both density and area decline with

Poster Abstracts

CROI 2020 258