Tags

Type your tag names separated by a space and hit enter

Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study.
AIDS. 2005 Sep 02; 19(13):1341-9.AIDS

Abstract

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.

Authors+Show Affiliations

Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA. todd.hulgan@vanderbilt.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16103764

Citation

Hulgan, Todd, et al. "Mitochondrial Haplogroups and Peripheral Neuropathy During Antiretroviral Therapy: an Adult AIDS Clinical Trials Group Study." AIDS (London, England), vol. 19, no. 13, 2005, pp. 1341-9.
Hulgan T, Haas DW, Haines JL, et al. Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study. AIDS. 2005;19(13):1341-9.
Hulgan, T., Haas, D. W., Haines, J. L., Ritchie, M. D., Robbins, G. K., Shafer, R. W., Clifford, D. B., Kallianpur, A. R., Summar, M., & Canter, J. A. (2005). Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study. AIDS (London, England), 19(13), 1341-9.
Hulgan T, et al. Mitochondrial Haplogroups and Peripheral Neuropathy During Antiretroviral Therapy: an Adult AIDS Clinical Trials Group Study. AIDS. 2005 Sep 2;19(13):1341-9. PubMed PMID: 16103764.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study. AU - Hulgan,Todd, AU - Haas,David W, AU - Haines,Jonathan L, AU - Ritchie,Marylyn D, AU - Robbins,Gregory K, AU - Shafer,Robert W, AU - Clifford,David B, AU - Kallianpur,Asha R, AU - Summar,Marshall, AU - Canter,Jeffrey A, PY - 2005/8/17/pubmed PY - 2006/4/6/medline PY - 2005/8/17/entrez SP - 1341 EP - 9 JF - AIDS (London, England) JO - AIDS VL - 19 IS - 13 N2 - 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. SN - 0269-9370 UR - https://www.unboundmedicine.com/medline/citation/16103764/Mitochondrial_haplogroups_and_peripheral_neuropathy_during_antiretroviral_therapy:_an_adult_AIDS_clinical_trials_group_study_ L2 - https://doi.org/10.1097/01.aids.0000180786.02930.a1 DB - PRIME DP - Unbound Medicine ER -