Genetic Polymorphisms Affecting the Pharmacokinetics of Antiretroviral Drugs

Abstract

Genetic polymorphisms may affect antiretroviral disposition, as well as both efficacy and toxicity. Despite a large amount of data, such precious knowledge has seldom been applied in patients. Studies on the clinical relevance and cost effectiveness of tailoring antiretroviral regimens to patients' genetic assets are lacking, but their importance may grow with the increasing age and complexity of persons living with HIV/AIDS.

The Influence of Pharmacogenetic Variants in HIV/Tuberculosis Coinfected Patients in Uganda in the SOUTH Study

“…Interindividual variability, tissue penetration, and drug–drug interactions are partially explained by genetic variants in genes encoding for drug metabolizing or transporting proteins. Single‐nucleotide polymorphisms (SNPs) are the most common genetic variants; they seldom influence protein expression or activity, whereas some genetic variants may affect the risk of developing certain diseases as well as the efficacy and tolerability of several compounds …”

“…Singlenucleotide polymorphisms (SNPs) are the most common genetic variants; they seldom influence protein expression or activity, whereas some genetic variants may affect the risk of developing certain diseases as well as the efficacy and tolerability of several compounds. 8,9 One of the first observed genetic variants of clinical consequence was the association between acetylator state (slow vs. fast) and INH toxicity. 10 Beyond polymorphisms of N-acetyltransferase 2 (NAT2 ) gene, several other SNPs have been associated with anti-TB drugs' exposure and toxicity.…”

Pharmacogenetic Analysis of the Model‐Based Pharmacokinetics of Five Anti‐HIV Drugs: How Does This Influence the Effect of Aging?

“…Gene polymorphisms play an important role in drug disposition and individualized therapy, as they can contribute to variability in pharmacokinetics (PKs), and may alter the effect of nongenetic factors. In HIV treatment, pharmacogenetic‐pharmacokinetic (PGx‐PK) relationships have been demonstrated for many antiretrovirals (ARVs) in the general population . Their roles in special populations, such as pregnancy and pediatrics, have also been evaluated.…”

“…It is also an inducer or inhibitor of CYP2B, CYP3A, and CYP2C . Transporters in the gut, such as P‐glycoprotein (P‐gp) and multidrug resistance proteins (MRPs), are presumably important globally to ARVs, which are mostly orally administrated . Organic anion‐transporting polypeptides (OATPs), which are enriched in the liver, could be relevant to ATV, RTV, and EFV, and OATs or organic cation transporters (OCTs) in the kidney are important to TFV or FTC .…”

“…16 Transporters in the gut, such as P-glycoprotein (P-gp) and multidrug resistance proteins (MRPs), are presumably important globally to ARVs, which are mostly orally administrated. 1 Organic anion-transporting polypeptides (OATPs), which are enriched in the liver, could be relevant to ATV, RTV, and EFV, and OATs or organic cation transporters (OCTs) in the kidney are important to TFV or FTC. 17 Nucleoside transporters, concentrative nucleoside transporters (CNTs) and equilibrative nucleoside transporters, are believed to transport nucleoside analogs, 1,17 which could be crucial to the disposition of TFV and FTC and the cellular accumulation of their active metabolites.…”