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-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 antiretrovi...
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th-mahidol.150992018-06-11T12:19:46Z 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 Sumonmal Uttayamakul Sirirat Likanonsakul Weerawat Manosuthi Nuanjun Wichukchinda Tatsuo Shioda Srisin Khusmith Mahidol University Thailand Ministry of Public Health Osaka University Medicine 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. 2018-06-11T05:19:46Z 2018-06-11T05:19:46Z 2012-01-01 Article Southeast Asian Journal of Tropical Medicine and Public Health. Vol.43, No.1 (2012), 78-88 01251562 2-s2.0-84856161693 https://repository.li.mahidol.ac.th/handle/123456789/15099 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84856161693&origin=inward |
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Medicine Sumonmal Uttayamakul Sirirat Likanonsakul Weerawat Manosuthi Nuanjun Wichukchinda Tatsuo Shioda Srisin Khusmith 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 |
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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. |
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Mahidol University |
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Mahidol University Sumonmal Uttayamakul Sirirat Likanonsakul Weerawat Manosuthi Nuanjun Wichukchinda Tatsuo Shioda Srisin Khusmith |
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Article |
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Sumonmal Uttayamakul Sirirat Likanonsakul Weerawat Manosuthi Nuanjun Wichukchinda Tatsuo Shioda Srisin Khusmith |
author_sort |
Sumonmal Uttayamakul |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/15099 |
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1763489639095599104 |