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摘要
The MDR1 genotype was analysed from 72 patients in whom antiretroviral therapy was initiated between 1998 and 2004. Data were obtained at week 4, 12, 24 and 48 and were analysed by the Kruskal-Wallis test.During the first 48 weeks of antiretroviral therapy, there were no significant differences in the virological and immunological response with respect to the MDR1 2677 and 3435 genotypes and the 2677/3435 haplotype.In view of different results from several studies concerning the influence of MDR1 polymorphisms on the immunological and virological response to antiretroviral therapy, further studies with larger patient groups and longer follow-up are necessary in order to resolve conflicting issues.The P-glycoprotein (P-gp) is an ATP-dependent efflux transporter (ABCB1) encoded by the multidrug resistance gene (MDR1) which extrudes large lipophilic, positvely charged molecules from cells, among them HIV-1 protease inhibitors [1,2]. P-gp is expressed on a variety of cells including human lymphocytes, the target cells of HIV and of antiretroviral substances [3]. 48 single nucleotide polymorphisms (SNP) have been described so far for the MDR1 gene [4]. Though there is still controversy about the biological relevance of these SNPs, there appears to be an association between specific genotypes and mRNA expression, P-gp expression and/or P-gp reviewed in [5,6]). Recently, Fellay et al. found lower nelfinavir and efavirenz plasma levels associated with the TT genotype of the SNP C3435T in exon 26 and a greater rise of the CD4 cell count 6 months after initiation of antiretroviral therapy in patients with this genotype [7]. However, the mechanisms underlying this observation remain unclear. In contrast to protease inhibitors (PI), non-nucleoside reverse transcriptase inhibitors (NNRTI) such as efavirenz are not substrates of the P-gp. Therefore, it has been speculated that the P-gp may modulate the clinical course of HIV infection independent from its role in drug t
