The Influence of Pharmacogenetic Variants in HIV/Tuberculosis Co-infected Patients in Uganda in the SOUTH Study

Unsatisfactory treatment outcomes have been reported in HIV/tuberculosis (TB) co-infected patients. Aim of this study was to assess the influence of single nucleotide polymorphisms (SNPs) in genes encoding for proteins involved in antitubercular drug disposition or effect. A pharmacogenetic study was conducted in Kampala, Uganda, where all analysis were performed. The impact of SNPs on antitubercular drugs exposure, adverse events and treatment outcomes was evaluated in HIV/TB co-infected subjects receiving treatments for both conditions. In 221 participants NAT2 (rs1799930), SLCO1B1 (rs4149032) and PXR (rs2472677) variants affected isoniazid exposure in multivariate analysis. Most patients were deemed cured (163, 73.8%), yet PXR 63396TT carriers had a higher probability of death (p=0.007) and of worsening peripheral neuropathy (p=0.018). In this exploratory study in Ugandan HIV/TB coinfected patients genetic variants in PXR, SLCO1B1 and NAT2 were moderately associated with isoniazid exposure while PXR 63396TT carriers showed worse outcomes. This article is protected by copyright. All rights reserved.