Mitochondrial DNA Haplogroups and Frailty in Adults Living with HIV.

Abstract

OBJECTIVE\nMitochondrial DNA (mtDNA) haplogroup has been associated with disease risk and longevity. Among persons with HIV (PWH), 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 PWH.\n\n\nMETHODS\nA cross-sectional analysis was performed of AIDS Clinical Trials Group A5322 (HAILO) participants with available genome-wide genotype and frailty assessments. Multivariable logistic regression models adjusted for age, sex, education, smoking, hepatitis C, and prior use of didanosine/stavudine.\n\n\nRESULTS\nAmong 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/\uf06dL; 6% were frail, 7% had slow gait and 21% weak grip. H haplogroup participants were more likely to be frail/pre-frail (p=0.064), have slow gait (p=0.09), or weak grip (p=0.017) compared to non-H haplogroup participants (not all comparisons reached statistical significance). In adjusted analyses, PWH with haplogroup H had a greater odds of being frail vs non-frail (OR 4.0 [95% CI 1.0, 15.4]) and having weak grip (OR 2.1 [1.1, 4.1]), but not slow gait (OR 1.6 [0.5, 5.0]) compared to non-H. Among black and Hispanic participants, haplogroup was not significantly associated with frailty, grip, or gait.\n\n\nCONCLUSIONS\nAmong ART-treated PWH, mtDNA haplogroup H was independently associated with weak grip and frailty. This association could represent a mechanism of weakness and frailty in the setting of HIV and ART.