title: Severe toxicity and polymerase-γ gene abnormalities in Malawian adults on stavudine-based antiretroviral therapy.
abstract: In a cohort study of Malawian adults who were followed up through their second year of stavudine-containing antiretroviral therapy, we sequenced the polymerase-γ gene (POLG) of 10 of the 14 patients with the most severe stavudine side effects. No mutations were observed, suggesting that monogenic POLG mutations are not a common pathogenic determinant of severe stavudine-associated mitochondrial toxicity in Malawians.
authors: aMalawi-Liverpool Wellcome Trust Clinical Research Programme Departments of bMedicine cPathology, College of Medicine, Blantyre dDignitas International, Zomba, Malawi eInstitute of Genetic Medicine, Newcastle University, Newcastle, UK fDivision of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors: Joep J
authors: JJ
authors: van Oosterhout
authors: Kristian
authors: K
authors: Gardner
authors: Jane
authors: J
authors: Mallewa
authors: Symon
authors: S
authors: Kaunda
authors: Elizabeth
authors: E
authors: Kampira
authors: Brendan
authors: B
authors: Payne
authors: Robert S
authors: RS
authors: Heyderman
authors: Patrick
authors: P
authors: Chinnery
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced / Q000235:genetics; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000187:drug effects; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008295:Malawi; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018119:Stavudine / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D018119:Stavudine; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human