Toxicogenetics of Antiretroviral Therapy: Genetic Factors that Contribute to Metabolic Complications

TL;DRAbstract

Metabolic complications of antiretroviral therapy (ART) have emerged as a major concern for long-term, successful management of HIV infection. Variability in the response to ART between individuals has been increasingly linked to the genetic background of patients, as regards efficacy and susceptibility to adverse reactions (toxicogenetics). This review summarizes the biological and methodological background for the genetic prediction of metabolic toxicity of ART. Recent studies are discussed which suggest that single-nucleotide polymorphisms (SNPs) in several genes involved in lipid metabolism and lipid transport in the general population (ABCA1, APOA5, APOC3, APOE, CETP) might modulate plasma triglyceride and high-density lipoprotein cholesterol levels in HIV-infected patients. At present, genetic prediction of lipodystrophy is not possible. Lipodystrophy has been linked to an accumulation of mtDNA mutations, a finding causally associated with ageing phenotypes in animal models. No m

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