Severe toxicity and polymerase-γ gene abnormalities in Malawian adults on stavudine-based antiretroviral therapy

Pharmacogenet Genomics. 2013 Nov;23(11):624-6. doi: 10.1097/FPC.0b013e3283655053.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / chemically induced
  • Acidosis, Lactic / genetics
  • Adult
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Cohort Studies
  • DNA Polymerase gamma
  • DNA, Mitochondrial / drug effects
  • DNA-Directed DNA Polymerase / genetics*
  • Female
  • Genetic Variation
  • HIV Infections / drug therapy
  • Humans
  • Malawi
  • Male
  • Middle Aged
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / genetics
  • Polymorphism, Single Nucleotide
  • Stavudine / adverse effects*
  • Stavudine / therapeutic use

Substances

  • Anti-HIV Agents
  • DNA, Mitochondrial
  • Stavudine
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human