97% of those with GT sellectchem genotype and 60% of those with GG genotype could achieve the HIV 1 RNA levels 50 copiesmL, but this Inhibitors,Modulators,Libraries difference also did not reach statisti cal significance Inhibitors,Modulators,Libraries due to small numbers of patients with homozygous TT genotype in this study. At weeks 24, 36 and 48 of ART, nearly all the patients achieved undetectable viral load, since viral load were not detected in 95. 38%, 93. 65% and 87. 9%, respectively, of efavirenz group and 96. 55%, 94. 64% and 94. 64%, respectively, of nevirapine group. Discussion This is the first report to demonstrate the effects of CYP2B6 G516T and CYP3A4 T878C polymorphisms on plasma efavirenz and nevirapine concentrations in rifampicin treated HIVTB co infected Thai adults.

The results indicated that the wide interindividual variability of efavirenz concentrations is strongly influenced by Inhibitors,Modulators,Libraries CYP2B6 516TT genotype by the finding of significantly higher plasma efavirenz concentration at weeks 6 and 12 of ART and 1 month after rifampicin discontinuation compared to those with GT or GG genotype. Likewise, it seems to be that this CYP2B6 516TT would also influence nevirapine concentrations, although it was less pronounced probably due to the small samples size of homozygous mutant TT in our sample set. The present results were in line with the previous report on efavirenz pharmacokinetics when co administration with rifampi cin in HIVTB co infected Indian and Ghana patients in that plasma efavirenz was highest in patients with CYP2B6 516TT genotype when compared to those with GT or GG genotypes.

While the heterozy gous TC mutant in CYP3A4 T878C in this study seems to have Inhibitors,Modulators,Libraries some Inhibitors,Modulators,Libraries effects on plasma drug concentrations in patients at weeks 6 and 12 of ART and 1 month after rifampicin discontinuation in both efavirenz and nevira pine groups, further statistical analysis was not done due to the relatively less variation inhibitor Vandetanib of CYP3A4 among Thai adults in this study. Further investigation should include a larger sample size with varying genotypes in order to draw a definite conclusion on the effect of CYP3A4 variations. In this study, the frequency of CYP2B6 G516T among 124 Thai adults was 8. 9%, which was close to that of our recent study on 237 HIV infected Thai adults with different rate of CD4 T cell recovery after ARV treat ment and slightly lower than what has been reported in Thai children. Comparing to the other ethnic groups, it was higher than those of Japanese and Cau casian. but lower than that of African Ameri can or African population. Although the frequencies of CYP2B6 G516T were differ ent among populations or ethnicity, the pharmacoge netic studies reported so far in HIV patients demonstrated that CYP2B6 516TT was definitely asso ciated with plasma efavirenz concentration.