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WEAK GRIP AND FRAILTY ARE ASSOCIATED WITH MTDNA HAPLOGROUP IN ADULTS WITH HIV
Kristine M. Erlandson1, Yuki Bradford2, David C. Samuels3, Todd T. Brown4, Jing Sun4, Kunling Wu5, Katherine Tassiopoulos5, Marylyn D. Ritchie2, David Haas3, Todd Hulgan3
1University of Colorado Anschutz Medical Campus, Aurora, CO, USA,2University of Pennsylvania, Philadelphia, PA, USA,3Vanderbilt University, Nashville, TN, USA,4Johns Hopkins University, Baltimore, MD, USA,5Harvard University, Boston, MA, USA
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.
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 ). 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.
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.)
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.