Efavirenz detectable in plasma 8 weeks after stopping therapy and subsequent development of non-nucleoside reverse transcriptase inhibitor-associated resistance

University of Liverpool, Liverpool, England, United Kingdom
AIDS (Impact Factor: 6.56). 11/2005; 19(15):1716-7. DOI: 10.1097/01.aids.0000186828.99032.60
Source: PubMed
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    ABSTRACT: Efavirenz-based antiretroviral therapy is recommended for prevention of mother-to-child transmission of HIV with two programmatic options: lifelong therapy for all women or treatment until cessation of breastfeeding. However, the risk of HIV resistance emerging after discontinuing efavirenz-based antiretroviral therapy is unclear. We review present knowledge surrounding the emergence of resistance after stopping efavirenz-based antiretroviral regimens. An expert review. A literature review was conducted to identify studies assessing risk for emergence of efavirenz-related resistance following discontinuation of efavirenz-based antiretroviral regimens containing either lamivudine and zidovudine or tenofovir disoproxil fumarate and lamivudine. Discontinuation strategies including the use of 'pharmacologic tails' are discussed in the light of what is known about the pharmacology of the drugs. We found no head-to-head comparisons between zidovudine, lamivudine and efavirenz and tenofovir disoproxil fumarate, lamivudine and efavirenz. The risk for HIV resistance exists, even with a 5-7 day tail of zidovudine and lamivudine. For tenofovir disoproxil fumarate, lamivudine and efavirenz, we found no clinical data to inform a recommendation for a tail. In order to prevent emergence of resistance, a tail of at least 2 weeks in duration may be required when discontinuing efavirenz in a regimen containing zidovudine and lamivudine. Studies are needed to characterize the risk of resistance among women who discontinue tenofovir disoproxil fumarate, lamivudine and efavirenz.
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    ABSTRACT: In clinical practice, antiretroviral regimens are often interrupted or modified for intolerance and toxicity. The objective of this study was to develop an in vitro to in vivo extrapolation (IVIVE) approach to describe the interaction when efavirenz is switched to either maraviroc or nevirapine and to test different switching scenarios to identify the best strategy.
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    ABSTRACT: Data on genetic polymorphisms associated with response to anti-HIV drugs has accumulated over the years. Information on how polymorphisms influence drug metabolism and transport to target sites is important in guiding dosage or selection of appropriate alternative therapies. This study determined the frequency of MDR1 C3435T and CYP2B6 G516T polymorphisms associated with the transport and metabolism of efavirenz and nevirapine, in a population of South African HIV infected patients. In addition, association of polymorphisms with immunologic and virologic factors was investigated. A 207bp of MDR1 exon 26 and a 161bp of CYP2B6 exon 4 were obtained from patients by polymerase chain reaction. Analysis of population-based sequences of MDR1 revealed a frequency of 89% and 11% of C and T alleles respectively (n=197; X ^{2} = 0.974; p=0.324). Restriction fragment length polymorphism (RFLP) analysis of the CYP2B6 gene revealed a prevalence of 9.5% of GG, 78.4% of GT and 12.1% of TT genotype (n= 199; X ^{2} = 65.204; p=0.00). There was no significant difference between immune recovery and decline in viral load (n=53), with genotype after repeated calculations of analysis of variance (ANOVA).
    Disease markers 02/2012; 32(1):43-50. DOI:10.3233/DMA-2012-0859 · 2.17 Impact Factor