Journal
PHARMACOGENOMICS
Volume 14, Issue 16, Pages 1999-2004Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/PGS.13.188
Keywords
dyslipidemia; lipodystrophy; mitochondrial DNA; subhaplogroups; toxicities
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Funding
- Wellcome Trust through the Health Research Capacity Strengthening Initiative
- Department for International Development (DFID) through the Health Research Capacity Strengthening Initiative
- Southern Africa Consortium for Research Excellence (SACORE)
- Medical Research Council (MRC) of South Africa
- National Research Foundation (NRF) of South Africa
- University of Cape Town
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Background & aim: Lipodystrophy remains a significant problem in HIV/AIDS patients, especially those on regimens containing either protease inhibitors or thymidine analogs (stavudine or zidovudine). Many of the manifestations of lipodystrophy have been linked to mitochondrial dysfunction. We set out to investigate whether mtDNA variation is associated with the development of stavudine-induced lipodystrophy among adult Malawian HIV/AIDS patients on antiretroviral therapy that included stavudine. Materials & methods: A total of 117 adult HIV/AIDS patients on stavudine-containing antiretroviral therapy (ART) were recruited from the ART clinic at the Queen Elizabeth Central Hospital, Malawi. The patients were categorized according to whether or not they had developed lipodystrophy after being on a stavudine-containing ART regimen for at least 6 months. Whole mtDNA-coding regions of each patient were sequenced and correlated with clinical characteristics. Results: Lipodystrophy was apparent in 16% (n = 19) of the participants. In multivariate analysis, age >40 years (odds ratio: 4.43; 95% CI: 1.36-14.47; p = 0.014) was significantly associated with the presence of lipodystrophy. The mtDNA subhaplogroup L3e appeared to be protective against lipodystrophy, as none of 11 subjects with this subhaplogroup presented with lipodystrophy. Conclusion: mtDNA subhaplogroups seem to differentially affect susceptibility to lipodystrophy. More research is required in order to identify patients who are more or less likely to benefit from stavudine-containing ART. Original submitted 28 June 2013; Revision submitted 16 September 2013
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