[Toxicogenetics of antiretroviral treatment (II): neurotoxicity, hepatotoxicity, lactic acidosis, kidney damage, and other adverse effects of antiretroviral drugs].
Several pharmacogenetics studies have analyzed the influence of specific genetic polymorphisms on the toxicity of antiretroviral treatment. The present review describes some of the adverse effects of antiretroviral drugs in which a genetic predisposition may be involved: efavirenz-induced neurological toxicity, generally associated with the 516G>T polymorphism of liver enzyme cytochrome P450 2B6 (CYP2B6); hypersensitivity reactions to nevirapine, associated with specific alleles of major histocompatibility complex, mainly the HLA-DRB1*0101 allele, which, in combination with a high CD4 lymphocyte count, has been associated with systemic reactions and hepatitis in Caucasians, and the HLA-Cw8 allele, which is associated with hypersensitivity reactions in persons from the Italian island of Sardinia and from Japan; nevirapine-induced hepatotoxicity associated with the C>T polymorphism in position 3435T of the ABCB1 (MDR-1) gene codifying for glycoprotein P (lower risk); hyperbilirubinemia in patients exposed to atazanavir or indinavir carrying the UGT1A1*28 polymorphism; peripheral neuropathy with nucleoside analogues associated with haplogroup T of the mitochondrial genome (higher risk) and with the HFE C282Y genotype of the hemochromatosis gene (lower risk); the mutation in codon 964 (R964C) of the POLG gene that codifies the mitochondrial polymerase DNA gamma described in a Thai patient with lactic acidosis; the ABCC2 gene haplotypes associated with tenofovir-induced proximal tubulopathy, and the risk of pancreatitis in persons with mutations in the CFTR and SPINK-1 genes.
Sánchez Hellín
Victoria
V
Unidad de Enfermedades Infecciosas, Hospital General Universitario de Elche, Alicante, España.
Gutiérrez Rodero
Félix
F
D000140:Acidosis, Lactic / Q000139:chemically induced; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D000089762:Multidrug Resistance-Associated Protein 2; D009422:Nervous System Diseases / Q000139:chemically induced; D043922:Toxicogenetics
C000715087:ABCC2 protein, human; D044966:Anti-Retroviral Agents; D000089762:Multidrug Resistance-Associated Protein 2