Mitochondrial DNA haplogroups influence lipoatrophy after highly active antiretroviral therapy.

Although highly active antiretroviral therapy (HAART) has been extremely effective in lowering AIDS incidence among patients infected with HIV, certain drugs included in HAART can cause serious mitochondrial toxicities. One of the most frequent adverse events is lipoatrophy, which is the loss of subcutaneous fat in the face, arms, buttocks, and/or legs as an adverse reaction to nucleoside reverse transcriptase inhibitors. The clinical symptoms of lipoatrophy resemble those of inherited mitochondrial diseases, which suggest that host mitochondrial genotype may play a role in susceptibility. We analyzed the association between mitochondrial haplogroup and severity of lipoatrophy in HIV-infected European American patients on HAART in the Multicenter AIDS cohort Study and found that mitochondrial haplogroup H was strongly associated with increased atrophy [arms: P = 0.007, odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.17 to 2.69; legs: P = 0.037, OR = 1.54, 95% CI = 1.03 to 2.31; and buttocks: P = 0.10, OR = 1.41 95% CI = 0.94 to 2.12]. We also saw borderline significance for haplogroup T as protective against lipoatrophy (P = 0.05, OR = 0.52, 95% CI = 0.20 to 1.00). These data suggest that mitochondrial DNA haplogroup may influence the propensity for lipoatrophy in patients receiving nucleoside reverse transcriptase inhibitors.
AuthorsSher L Hendrickson, Lawrence A Kingsley, Eduardo Ruiz-Pesini, Jason C Poole, Lisa P Jacobson, Frank J Palella, Jay H Bream, Douglas C Wallace, Stephen J O'Brien
JournalJournal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 51 Issue 2 Pg. 111-6 (Jun 1 2009) ISSN: 1525-4135 [Print] United States
PMID19339895 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-HIV Agents
  • DNA, Mitochondrial
  • Adolescent
  • Adult
  • Aged
  • Anti-HIV Agents (adverse effects, therapeutic use)
  • Antiretroviral Therapy, Highly Active
  • DNA, Mitochondrial (genetics)
  • Genetic Predisposition to Disease
  • HIV-1
  • HIV-Associated Lipodystrophy Syndrome (chemically induced, genetics)
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Phyllachorales
  • Polymorphism, Single Nucleotide
  • Young Adult

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