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.
ATP-binding cassette, sub-family B (encoded by ABCB-1 or 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.
Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Sumonmal
S
Uttayamakul
Sirirat
S
Likanonsakul
Weerawat
W
Manosuthi
Nuanjun
N
Wichukchinda
Tatsuo
T
Shioda
Srisin
S
Khusmith
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000480:Alkynes; D000704:Analysis of Variance; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000097:blood; D048588:Benzoxazines / Q000097:blood*; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000097:blood*; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction; D012293:Rifampin / Q000097:blood; D013785:Thailand; D014376:Tuberculosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D019562:Viral Load
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000480:Alkynes; D000995:Antitubercular Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D019829:Nevirapine; C098320:efavirenz; D012293:Rifampin