CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

1 Northwestern University, Chicago, IL, USA, 2 Harvard University, Boston, MA, USA, 3 DAIDS, NIAID, Rockville, MD, USA, 4 University of California San Diego, San Diego, CA, USA, 5 Columbia University, New York, NY, USA, 6 Johns Hopkins University, Baltimore, MD, USA, 7 University of Colorado, Aurora, CO, USA Background: Neurocognitive impairment (NCI) and impaired glucose metabolism have been associated with decline in gait speed in the general population. Gait speed declines more in people living with HIV (PLWH) compared to uninfected persons, but factors related to this functional outcome are limited to a single cohort of men. Methods: AIDS Clinical Trials Group (ACTG) A5322 (HAILO) is an observational cohort study of PLWH ≥ 40 years old that includes semi-annual laboratory tests and annual cognitive and gait speed assessments. Slowness was defined as gait speed of >4 seconds on 4-mwalk. Participants who developed slowness during the first 3 years were compared to persons who maintained normal speed. We used multivariable logistic regression to assess associations between development of slowness and baseline covariates including age, sex, race, alcohol use, BMI, waist circumference, nadir CD4, history of AIDS defining illness, hemoglobin A1C (HbA1C), and NCI (≥1 z-score ≥2 SD below 0 or ≥2 z-scores ≥1 SD below 0 on Trailmaking A and B and the Wechsler Adult Intelligence Scale- Revised Digit Symbol tests). Results: Of 929 participants, 81%were male, 31% Black, and 20% Hispanic. Median age was 51 years (IQR 46-56). Most individuals (91.9%) had undetectable plasma HIV RNA (VL <50 copies/mL) with median CD4 count 631 cells/mm³ (IQR 458-840) at study entry. At study entry, 7% of participants had slow gait, 16% had NCI, 12% had diabetes. Over 3 years, 6% of participants developed a slow gait and 87%maintained a normal gait. In multivariable models, HbA1C percentage, per 1% change (OR 1.40; 95% CI=1.06, 1.85; p=0.019), NCI (OR 3.38; 95% CI=1.53, 7.46; p=0.003), and black vs white race (OR 2.34; 95% CI=1.03, 5.29; p=0.042) at entry were significantly associated with increasing prevalence of slowness compared to those maintaining normal gait speed. Conclusion: The association between baseline hemoglobin A1C and development of slow gait speed highlights an intervenable target to prevent progression of physical function limitations. Additionally, the presence of NCI among PLWH should prompt screening for and early intervention to avert declines in physical function. 704 SERIOUS INJURY AFTER A FALL: ARE THOSE WITH HIV AT GREATER RISK THAN UNINFECTED? Julie A. Womack 1 , Christine Ramsey 1 , Terrence E. Murphy 2 , Harini Bathulapalli 2 , Alexandria C. Smith 2 , Cynthia L. Gibert 3 , Maria Rodriguez-Barradas 4 , Phyllis Tien 5 , Michael T. Yin 6 , Thomas M. Gill 2 , Gary Friedlaender 2 , Cynthia A. Brandt 1 , Amy C. Justice 2 1 VA Connecticut Healthcare System, West Haven, CT, USA, 2 Yale University, New Haven, CT, USA, 3 Washington DC VA Medical Center, Washington, DC, USA, 4 Michael E. DeBakey VA Medical Center, Houston, TX, USA, 5 University of California San Francisco, San Francisco, CA, USA, 6 Columbia University Medical Center, New York, NY, USA Background: HIV infected (HIV+) Veterans 50+ years of age are more likely to fall than uninfected comparators. Whether they are at greater risk for serious injury after the fall is not known. Methods: We used data from the Veterans Aging Cohort Study (VACS). The primary exposures were HIV and falls. The outcome was serious injury as identified by ICD9 codes (hip fracture, fragility fracture, joint dislocation, traumatic brain injury (TBI), and head injury). We identified medically significant falls using Ecodes and a machine learning algorithm applied to radiology reports. After verifying that associations between HIV and each type of serious injury were similar, all injuries were merged into a composite outcome. An interaction term between HIV and falls assessed whether falls had a differential impact on the risk of injury among HIV+ and uninfected participants. The analytic unit was a six-month person-interval. Covariates assessed at the beginning of the interval were evaluated for associations with occurrence of a serious injury in that interval. Multivariable logistic regression was used to evaluate the associations of HIV and falls with serious injury with adjustment for risk factors for fall-related injury identified among older adults and for disease severity with the VACS Index. Results: Our analysis included 73,283 Veterans who were 50+ years of age, 31% of whomwere HIV+. Fall incidence was 46 per 1000 person-years (95% CI 45-47 per 1000 person-years) for HIV+ and 40 per 1000 person-years (95% CI

702 WEAK GRIP AND FRAILTY ARE ASSOCIATED WITH MTDNA HAPLOGROUP IN ADULTS WITH HIV Kristine M. Erlandson 1 , Yuki Bradford 2 , David C. Samuels 3 , Todd T. Brown 4 , Jing Sun 4 , Kunling Wu 5 , Katherine Tassiopoulos 5 , Marylyn D. Ritchie 2 , David Haas 3 , Todd Hulgan 3 , for the AIDS Clinical Trials Group 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 University of Pennsylvania, Philadelphia, PA, USA, 3 Vanderbilt University, Nashville, TN, USA, 4 Johns Hopkins University, Baltimore, MD, USA, 5 Harvard University, Boston, MA, USA Background: Mitochondrial DNA (mtDNA) haplogroups have been associated with disease risk and longevity, perhaps as a marker of mitochondrial function. Among persons living with HIV (PLWH), mitochondria may be affected by HIV itself and antiretroviral therapy; mtDNA haplogroup has been associated with AIDS progression, neuropathy, cognitive impairment, and gait speed decline. We sought to determine if haplogroup is associated with frailty and its components among older PLWH. Methods: A cross-sectional analysis was performed of AIDS Clinical Trials Group A5322 (HAILO) participants with available genome-wide genotype and frailty phenotype assessments. Frailty included weight loss, fatigue, low activity, weakness, and slowness, and was considered as continuous (0-5) or categorical (frail [3-5 components], pre-frail [1-2], non-frail [0]). Weakness (grip) and slowness (4-meter gait) were considered separately, using sex and body mass index (grip) or height (gait) cut-points. Multivariable models adjusted for age, sex, education, smoking, hepatitis C, and prior use of didanosine/stavudine. Results: Among 634 participants, 81%were male, 49% non-Hispanic white, 31% non-Hispanic black, and 20% Hispanic. Mean age was 51.0 (SD 7.5) years and median nadir CD4 count 212 (IQR 72, 324) cells/μL. Thirty-five (6%) were frail and 244 (39%) pre-frail; 7% had slow gait (mean speed 4.0 sec/4m) and 21%weak grip. Of 13 frail white participants, 10 were from European mtDNA haplogroup H (p=0.059); similarly, among 46 with weak grip, 30 were H (p=0.015). In adjusted analyses, PLWH with haplogroup H tended towards higher frailty score (β=0.090 points; p= 0.058) and weaker grip (β=-0.37 kg; p=0.028), but not slower gait (β=-0.022 seconds; p=0.65) compared to non-H. Among 199 black participants, haplogroups were not associated with frailty, grip strength, or gait speed. Among 125 Hispanic participants, 6 were frail and 4 had slow gait; all were from non-major Hispanic haplogroups (p=0.06 and p=0.10, respectively.) Conclusion: In this analysis of ART-treated PLWH, European mtDNA haplogroup H was independently associated with weak grip and frailty versus with non-H European haplogroups. Mechanisms may include primary effects on mitochondrial function in skeletal muscle or indirectly through neurologic pathways, and warrants further study. This association has not been reported among people without HIV, thus could represent a unique contribution of HIV to weakness and frailty. 703 GLYCEMIC CONTROL AND COGNITION ARE INDEPENDENTLY ASSOCIATED WITH GAIT SPEED DECLINE Mary Clare Masters 1 , Jeremiah Perez 2 , Katherine Tassiopoulos 2 , Adriana Andrade 3 , Ronald J. Ellis 4 , Jingyan Yang 5 , Todd T. Brown 6 , Frank J. Palella 1 , Kristine M. Erlandson 7

Poster Abstracts

CROI 2019 270