Discordant associations between SLCO1B1 521T→C and plasma levels of ritonavir-boosted protease inhibitors in AIDS clinical trials group study A5146.

ABSTRACT:

Objective

Among HIV-positive patients prescribed ritonavir-boosted lopinavir, SLCO1B1 521T→C (rs4149056) is associated with increased plasma lopinavir exposure. Protease inhibitors (PIs) are also substrates for cytochrome P450 (CYP) 3A and ABCB1, which are induced by NR1I2. We characterized relationships between ABCB1, CYP3A4, CYP3A5, NR1I2, and SLCO1B1 polymorphisms and trough PI concentrations among AIDS Clinical Trials Group study A5146 participants.

Methods

At study entry, subjects with virologic failure on PI-containing regimens initiated new ritonavir-boosted PI regimens. We studied associations between week 2 PI plasma trough concentrations and 143 polymorphisms in these genes, including 4 targeted polymorphisms.

Results

Among 275 subjects with both drug concen

SUBMITTER: Zhang X 

PROVIDER: S-EPMC3603284 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature