Journal
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
Volume 51, Issue 2, Pages 111-116Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e3181a324d6
Keywords
lipoatrophy; mitochondrial haplogroup; mitochondrial toxicity; NRTI
Categories
Funding
- NCRR NIH HHS [M01 RR000722-23, M01 RR000722, M01 RR000425, S07 RR018241-01, M01 RR00425, 5-M01-RR-00722] Funding Source: Medline
- NIAID NIH HHS [U01 AI035040-16, U01 AI035039-10, U01 AI035041-07, U01-AI-35042, U01 AI035039-13, U01 AI035039-07, U01 AI035039-12, U01 AI035039-15, U01-AI-35041, U01 AI037613, U01 AI035040-15, U01-AI-37613, U01 AI035039-11, U01 AI035040-10, U01 AI035042, U01-AI-37984, U01 AI035039, U01 AI035040-14, U01 AI035039-17, U01 AI035043, U01 AI037984, U01-AI-35043, U01-AI-35040, U01 AI035039-09S1, U01 AI037613-08, U01 AI035041, U01 AI035039-09, U01 AI035040-12, U01 AI035040-11S1, U01 AI035040-08, U01 AI035039-08, U01 AI035039-16, U01 AI035042-08, U01 AI035040-13, U01 AI035040, U01 AI035040-17, U01-AI-35039, U01 AI035040-11, U01 AI035039-14] Funding Source: Medline
- NIA NIH HHS [AG25638, AG24373, R01 AG024373-05, F32 AG025638, P50 AG016573, F32 AG025638-02, AG16573, R01 AG024373] Funding Source: Medline
- NIDDK NIH HHS [DK73691, R01 DK073691-04, R01 DK073691] Funding Source: Medline
- NINDS NIH HHS [NS21328, R01 NS021328-16, R01 NS021328] Funding Source: Medline
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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.
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