Li et al (2011) pooled analysis reported that the presence of any NNRTI-resistance or NRTI-resistance minority variation was connected with an expanded risk of virologic failure. Their other from cohort studies uncovered virologic failure in 40% of patients with medication resistance minority mutations compared with 17% in those with no minority variations (Li et al., 2011). What’s more, it has been watched, using test with the highest sensitivity to detect resistance minority mutations, which roughly 11 patients would have to be screened before starting of antiretroviral treatment containing NNRTI to anticipate one case of virologic disappointment (Johnson et al., 2008). Since NNRTIs are ordinarily recommended in first-line regimens, this discovery supports a rationale for ultra-sensitive screening test for HIV drug resistance variations before starting antiretroviral treatment to distinguish subjects at higher danger of virologic failure (Li et al., 2011).
5. ROLE OF PHARMACOGENETICS IN ANTIRETROVIRAL METABOLISM AND TRANSPORT
The noticed inter-subject variations in the pharmacokinetics of antiretroviral medications also have an important role with respect both to the efficacy and the toxicity of these agents. Following the administration of the standard dose of antiretroviral medications, a lot of inter-subject variability in concentrations of plasma drug has been accounted for (Owen et al., 2006). The enzymes that are in charge of the metabolism of these agents and the proteins included in their transport are the real determinants of what happens to a medication once it is in the body. Host environmental and genetic factors, for example, drug-drug interaction, sex, weight, and the presence of comorbidities can also influence enzyme and transporter activity and, therefore, the disposition of antiretroviral operators.
5.1 PHARMACOKINETICS
The process that manage drug absorption, for example, the intestinal-hepatic first-pass effect, metabolism, dispersion (systemic and tissue) and excretion are significant determinants of drug concentrations of plasma and tissue. The greater part of antiretroviral drugs is directed orally and absorbed through intestinal epithelial cells and these cells express various membrane-bounded proteins that proceed as selective drug transporters, which locally decide absorption quantities. In addition, enterocytes contain large amounts of enzymes that can biotransform drugs (Boffito et al., 2003).
The portion of the drug absorbed from the intestine tract goes to the liver by means of the mesenteric veins and after that by the portal vein to the liver. In hepatocytes, the medication is at the end subjected to transport and metabolism before it arrives the systemic circulation. Together, these procedures describe the effects of the first intestinal-hepatic pass which decides a drug’s systemic bioavailability. When it is in the systemic circulation, and relying upon the molecule’s inherent physiochemical properties, the medication is circulated to different tissues that empower the antiretroviral agents to go to certain HIV sanctuary locations.
