Influence of ABCB-1 C3435T polymorphisms on plasma nevirapine and efavirenz levels and their effects on virologic and immunological outcomes in HIV/TB co-infected thai adults under anti-retroviral therapy

Abstract

ATP-binding cassette, sub-family B (encoded by ABCB-1or MDR-1) has an important role in cellular export of antiretroviral agents. A previous study showed that ABCB-1 C3435T polymorphism affects plasma efavirenz and nelfinavir concentrations and rate of CD4+ T cell recovery after starting antiretroviral treatment (ART). The present study examined the influence of ABCB-1 polymorphisms on plasma nevirapine and efavirenz levels when co-administered with rifampicin in 124 HIV/TB patients who received nevirapine- (400 mg/day) (n = 59) and efavirenz- (600 mg/day) (n = 65) based ART. ABCB-1 C3435T polymorphisms were genotyped using real-time PCR. CD4 T cell counts and HIV-1 viral RNA were evaluated in response to ART. The frequencies of CC, CT and TT genotypes of ABCB-1 C3435T polymorphism were 34% (n = 42), 55% (n = 68) and 12% (n = 14), respectively. Contrary to the previous report, no association was found among these genotypes and plasma drug concentrations at weeks 6 and 12 of ART and after rifampicin discontinuation. We also observed no differences in CD4+ T cell recovery rate among different ABCB-1 C3435T genotypes. In nevirapine group, however, all the patients with CT genotype achieved HIV-1 RNA levels of < 50 copies/ml, while 67% of those with TT and 95% with CC genotypes achieved < 50 copies/ml (p = 0.040). These data suggested that ABCB-1 C3435T polymorphisms do not affect plasma nevirapine and efavirenz concentrations in HIV/TB co-infected Thai patients or their immunological outcome, but had an effect on virologic outcome in the nevirapine-treated group.