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Mitochondrial DNA Haplogroups and Frailty in Adults Living with HIV.

  • Erlandson, Kristine M1
  • Bradford, Yuki2
  • Samuels, David C3
  • Brown, Todd T4
  • Sun, Jing4
  • Wu, Kunling5
  • Tassiopoulos, Katherine6
  • Ritchie, Marylyn D2
  • Haas, David W7, 8
  • Hulgan, Todd7
  • 1 Division of Infectious Diseases, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado.
  • 2 Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • 3 Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
  • 4 Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
  • 5 Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
  • 6 Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
  • 7 Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
  • 8 Internal Medicine, Meharry Medical College, Nashville, Tennessee.
Published Article
AIDS Research and Human Retroviruses
Mary Ann Liebert
Publication Date
Mar 01, 2020
DOI: 10.1089/AID.2019.0233
PMID: 31822125


Mitochondrial 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 whether haplogroup is associated with frailty and its components among older PWH. A 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, gender, 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 (standard deviation 7.5) years and median nadir CD4 count was 212 (interquartile range 72, 324) cells/μL; 6% were frail, 7% had slow gait, and 21% weak grip. H haplogroup participants were more likely to be frail/prefrail (p = .064), have slow gait (p = .09), or weak grip (p = .017) compared with non-H haplogroup participants (not all comparisons reached statistical significance). In adjusted analyses, PWH with haplogroup H had a greater odds of being frail versus nonfrail [odds ratio (OR) 4.0 (95% confidence interval 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 with non-H haplogroup. Among black and Hispanic participants, haplogroup was not significantly associated with frailty, grip, or gait. Among antiretroviral therapy (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.

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