Mitochondrial DNA Haplogroups Influence AIDS Progression

Objective: Mitochondrial function plays a role in both AIDS progression and HAART toxicity; therefore, we sought to determine whether mitochondrial DNA variation revealed novel AIDS restriction genes, particularly as mitochondrial DNA singlenucleotide polymorphisms are known to influence regulation of oxidative phosphorylation, reactive oxygen species production, and apoptosis. Design: This is a retrospective cohort study. Methods: We performed an association study of mitochondrial DNA haplogroups among 1833 European American HIV-1 patients from five US cohorts: the Multicenter AIDS Cohort Study, the San Francisco City Clinic Study, Hemophilia Growth and Development Study, the Multicenter Hemophilia Cohort Study, and the AIDS Linked to Intravenous Experiences cohort to determine whether the mitochondrial DNA haplogroup correlated with AIDS progression rate. Results: Mitochondrial DNA haplogroups J and U5a were elevated among HIV-1 infected people who display accelerated progression to AIDS and death. Haplogroups Uk, H3, and IWX appeared to be highly protective against AIDS progression. Conclusion: The associations found in our study appear to support a functional explanation by which mitochondrial DNA variation among haplogroups, influencing ATP production, reactive oxygen species generation, and apoptosis, is correlated to AIDS disease progression; however, repeating these results in cohorts with different ethnic backgrounds would be informative. These data suggest that mitochondrial genes are important indicators of AIDS disease progression in HIV-1 infected persons

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