AIDS reviews
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Administration of standard doses of most antiretroviral drugs results in significant variations in plasma drug concentrations among different individuals, as well as different rates of drug-associated toxicity. The reasons for the large interindividual variability in drug levels are multifactorial, and involve differences in gender metabolism, concomitant medications, drug compliance, underlying diseases, and genetic factors. Pharmacogenetics is the discipline that analyses the genetic basis for the interindividual variation in the body disposition of drugs. ⋯ This variation is due to polymorphisms in the N-acetyltransferase-2 (NAT2) gene, which may split the population into three categories: slow, intermediate, and fast metabolizers. Pharmacogenetic studies conducted so far with antiretrovirals have focused on metabolizing enzymes and transporter proteins in the cell membrane. Herein, we review the genetic polymorphisms known to be associated with altered pharmacokinetics of antiretrovirals, which may influence the efficacy and toxicity of these drugs.
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Antiretroviral (ARV) drugs have become the cornerstone of care and treatment for AIDS in North America, Brazil, and Europe. Twenty years into the epidemic, and more than 10 years after the introduction of ARV's, effective global treatment of AIDS, particularly in sub-Saharan Africa where the epidemic is most concentrated, is an extraordinary challenge. ⋯ Implementation of safe, effective, and equitable access to ARV's in Africa should be cognizant of the guidelines for ARV treatment in the Northern countries. Careful observation and operational research to accrue more African data, and evaluate regional and local solutions to this daunting challenge, will identify new approaches to scaling-up of ARV treatment.