CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

872

Mitochondrial DNA Variation and Physical Function Among Men With and Without HIV Jing Sun 1 , Weiqun Tong 1 , Wen Shi 2 , Kristine M. Erlandson 3 , Beth Jamieson Karavodin 4 , Frank Palella 5 , Jennifer Schrack 1 , Todd Hulgan 6 , Dan E. Arking 2 , Todd Brown 2 , for the MACS/WIHS Combined Cohort Study (MWCCS) 1 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 3 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 4 University of California Los Angeles Medical Center, Los Angeles, CA, USA, 5 Northwestern University, Chicago, IL, USA, 6 Vanderbilt University Medical Center, Nashville, TN, USA Background: Mitochondrial DNA variation is associated with multiple aging-related comorbidities among people with HIV (PWH). Data on the effect of inherited mitochondrial DNA variants on physical function among PWH are limited. Methods: We included men with ≥2 visits from the Multicenter AIDS Cohort Study. Gait speed and grip strength were evaluated twice annually using standard methods beginning in 2006. Gait speed was defined as the fastest of 2 attempts over a 4-meter distance. Grip strength was the average across three measures with the dominant hand. We categorized all participants into 7 distinct functionally informed mitochondrial DNA (mtDNA) haplotypes, previously validated in the UK Biobank, annotated based on mtDNA SNPs: MT73, MT7028, MT10238, MT12612, MT1317, and MT15257. Less than 5% of the participants were categorized in the other haplotypes and were not included in the analysis. Mixed effect linear regressions evaluated the association of haplotypes with gait speed and grip strength. Models controlled for principal components of ancestry, common mtDNA haplogroups, baseline age, time, BMI, socioeconomic status, risk behavior (smoking, alcohol, injection drug use), and number of comorbidities. Results: Of 2314 men (1277 PWH) with 38,913 person-years of follow-up, 26% were Black, 59% White; median age at baseline was 47 years [IQR: 40, 54]. Compared to the reference haplotype (2_2_2_2_2_2 based on the listed mtDNA SNPs), haplotype I was associated with slower gait speed (-0.03 m/s [95% CI: -0.05, -0.01]) and haplotype II, III, IV, and V were associated with faster gait speed (all p<0.05). Compared to the reference haplotype, haplotypes I, IV, and VII were associated with greater grip strength (1.22 kg [95% CI: 0.15, 2.29], 1.16 kg (95% CI: 0.11, 2.21), and 1.70 kg [95% CI: 1.13, 2.28]). The association of haplotypes and gait speed differed by HIV serostatus in haplotype III and VII ( Figure, panel A ). All haplotypes except haplotype I and VII differed by HIV status for grip strength ( Figure, Panel B ). Results were consistent in the stratified analyses among European ancestry men. Conclusions: Functionally informed mtDNA haplotypes were associated with gait speed and grip strength in men. But the direction of these associations varied based on HIV status, indicating that each haplotype has distinct functional implications. Further investigation into the underlying mechanisms of mtDNA variation and its impact on physical function in the context of HIV status is warranted.

871

Validation of SARC-F Tool for Sarcopenia Screening in People Aging With HIV Joselito Malca Hernandez 1 , Noah Brazer 1 , Ahmed Abdeen 2 , Daniel Granda 3 , Yvett Pinedo Ramirez 4 , Flor Gonzales 5 , Miguel Tapia 5 , Patricia Garcia 3 , Evelyn Hsieh 1 1 Yale University, New Haven, CT, USA, 2 Pennsylvania State University, Hershey, PA, USA, 3 Universidad Peruana Cayetano Heredia, Lima, Peru, 4 Hospital Nacional Arzobispo Loayza, Lima, Peru, 5 Centro de Referencias de Infecciones de Transmisión Sexual (CERITS), Lima, Peru Background: Prior studies have shown that persons aging with HIV are at higher risk for sarcopenia. Several consensus definitions have been developed for sarcopenia based upon combined muscle mass, performance and strength assessments. Because these approaches are not practical for routine clinical settings, the 5-item SARC-F questionnaire was validated to screen for sarcopenia in the general population (GP) but has not yet been validated for people living with HIV (PLWH). Methods: We conducted a cross-sectional study of PLWH aged ≥45 years at three HIV clinics in Lima, Peru between March 2022 to August 2023. Patients completed demographic and clinical surveys, the validated Spanish language SARC-F (score range: 0-10, score ≥4 indicating a high likelihood of sarcopenia or severe sarcopenia), the Short Physical Performance Battery, grip strength, and a dual-energy x-ray absorptiometry body composition scan for appendicular skeletal muscle index. Sarcopenia spectrum (presarcopenia, sarcopenia, and severe sarcopenia) was classified based on the European Working Group on Sarcopenia in Older People (EWGSOP 2019) and the Asian Working Group on Sarcopenia (AWGS) reference standards. Sex-based differences in presence of sarcopenia spectrum were analyzed using χ2 or Fisher’s exact tests. Validity of SARC-F to identify individuals with sarcopenia or severe sarcopenia, compared to EWGSOP 2019 and AWGS, was assessed with sensitivity, specificity, positive and negative predictive values (PPV/NPV), and area under the receiver operating curve (AUC). Results: We enrolled 210 PWH, including 105 women, 105 men, with mean ages of 55.2±7.1 and 54.8±7.6, respectively. Sarcopenia spectrum prevalence was higher amongwomen compared with men based upon EWGSOP 2019 and AWGS. 22.7% of participants had a SARC-F score ≥4. Table 1 shows the validity results of SARC-F compared to each criterion. Conclusions: In our study, using a cutoff of 4, SARC-F showed acceptable specificity, low sensitivity and low-moderate discrimination. Given sarcopenia spectrum was present in 30-35% of participants, further research is warranted to evaluate how SARC-F or other tools can support detection of sarcopenia in settings where multi-component tests are not feasible.

Poster Abstracts

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