title: Mitochondrial subhaplogroups and differential risk of stavudine-induced lipodystrophy in Malawian HIV/AIDS patients.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Human Genetics, Department of Clinical Laboratory Sciences, Faculty of Health Science, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kampira
authors.forename: Johnstone
authors.initials: J
authors.lastname: Kumwenda
authors.forename: Joep J
authors.initials: JJ
authors.lastname: Van Oosterhout
authors.forename: Collet
authors.initials: C
authors.lastname: Dandara
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000821:virology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006678:HIV / Q000235:genetics / Q000472:pathogenicity; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008060:Lipodystrophy / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics* / Q000473:pathology; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004272:DNA, Mitochondrial; D018119:Stavudine