AUTHOR=Swart Marelize , Ren Yuan , Smith Peter , Dandara Collet 

TITLE=ABCB1 4036A>G and 1236C>T Polymorphisms Affect Plasma Efavirenz Levels in South African HIV/AIDS Patients

JOURNAL=Frontiers in Genetics

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2012.00236

DOI=10.3389/fgene.2012.00236

ISSN=1664-8021

ABSTRACT=<p>The <italic>ABCB1</italic> gene encodes P-glycoprotein, an ATP-dependent drug efflux pump, which is responsible for drug transport across extra- and intra-cellular membranes. The variability in the expression of <italic>ABCB1</italic> may contribute to variable plasma efavirenz concentration which results in variability in the levels of suppression of the human immunodeficiency syndrome virus (HIV). The aim of the study was to evaluate the role of polymorphisms in <italic>ABCB1</italic> gene on plasma efavirenz levels and treatment response in the form of change in viral load and CD-4 cell count in HIV/AIDS patients receiving efavirenz-containing highly active antiretroviral treatment regimens. Two hundred and eighty-two HIV-infected patients were recruited from Themba Lethu Clinic in Johannesburg and plasma efavirenz drug concentration levels were measured using LC-MS/MS. SNaPshot was used to genotype five known <italic>ABCB1</italic> single nucleotide polymorphisms (SNPs). Genotype-phenotype correlations were computed. The <italic>ABCB1 4036A/G</italic> and <italic>4036G/G</italic> genotypes were significantly associated with low plasma efavirenz concentrations (<italic>P</italic> = 0.0236), while the <italic>ABCB1 1236C/T</italic> and <italic>1236T/T</italic> genotypes were associated with high efavirenz concentrations (<italic>P</italic> = 0.0282). A haplotype <italic>ABCB1 T-G-T-A</italic> is reported that is associated with significantly increased plasma efavirenz levels. This is the first report on <italic>61A</italic>&gt;<italic>G</italic>, <italic>2677G</italic>&gt;<italic>T/A</italic>, and <italic>4036A</italic>&gt;<italic>G</italic> SNPs in the South African population. <italic>ABCB1</italic> plays a role in determining the plasma concentrations of efavirenz and should be taken into account in future design of assays for genotype-based dosing of efavirenz-containing regimens.</p>