Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study.

Hulgan T, Haas DW, Haines JL, Ritchie MD, Robbins GK, Shafer RW, Clifford DB, Kallianpur AR, Summar M, Canter JA
AIDS. 2005 19 (13): 1341-9

PMID: 16103764 · DOI:10.1097/01.aids.0000180786.02930.a1

OBJECTIVE - HIV nucleoside reverse transcriptase inhibitors (NRTI) can cause peripheral neuropathy that is a result of mitochondrial injury. Polymorphisms in the mitochondrial genome define haplogroups that may have functional implications. The objective of this study was to determine if NRTI-associated peripheral neuropathy is associated with European mitochondrial haplogroups.

DESIGN - Case-control study of Adult AIDS Clinical Trials Group (ACTG) study 384 and ACTG Human DNA Repository participants.

METHODS - ACTG study 384 was a treatment strategy trial of antiretroviral therapy with didanosine (ddI) plus stavudine (d4T) or zidovudine plus lamivudine given with efavirenz, nelfinavir, or both. Subjects were followed for up to 3 years. Peripheral neuropathy was ascertained based on signs and symptoms. For this analysis, polymorphisms that define European mitochondrial haplogroups were characterized in a majority of ACTG 384 participants, and associations with peripheral neuropathy were assessed using logistic regression.

RESULTS - A total of 509 subjects were included in this analysis of whom 250 (49%) were self-identified as white, non-Hispanic. Mitochondrial haplogroup T was more frequent in subjects who developed peripheral neuropathy. Among 137 white subjects randomized to receive ddI plus d4T, 20.8% of those who developed peripheral neuropathy belonged to mitochondrial haplogroup T compared to 4.5% of control subjects (odds ratio, 5.4; 95% confidence interval, 1.4-25.1; P = 0.009). Independent predictors of peripheral neuropathy were randomization to receive ddI plus d4T, older age, and mitochondrial haplogroup T.

CONCLUSIONS - A common European mitochondrial haplogroup may predict NRTI-associated peripheral neuropathy. Future studies should validate this relationship, and evaluate non-European mitochondrial haplogroups and other NRTI toxicities.

MeSH Terms (19)

Adolescent Adult Aged Anti-HIV Agents Antiretroviral Therapy, Highly Active Case-Control Studies DNA, Mitochondrial Female Genetic Predisposition to Disease Haplotypes HIV-1 HIV Infections Humans Male Middle Aged Peripheral Nervous System Diseases Polymorphism, Genetic Reverse Transcriptase Inhibitors Risk Factors

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