The Influence of Pharmacogenetic Variants in HIV/Tuberculosis Coinfected Patients in Uganda in the SOUTH Study

Unsatisfactory treatment outcomes have been reported in patients coinfected with HIV/tuberculosis (TB). The 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...

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Vydané v:Clinical pharmacology and therapeutics Ročník 106; číslo 2; s. 450
Hlavní autori: Calcagno, Andrea, Cusato, Jessica, Sekaggya-Wiltshire, Christine, von Braun, Amrei, Motta, Ilaria, Turyasingura, Grace, Castelnuovo, Barbara, Fehr, Jan, Di Perri, Giovanni, Lamorde, Mohammed
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 01.08.2019
Predmet:
Adult
Antitubercular Agents - adverse effects
Antitubercular Agents - pharmacokinetics
Arylamine N-Acetyltransferase - genetics
Correlation of Data
Female
HIV Infections - epidemiology
HIV Infections - genetics
HIV Infections - therapy
Humans
Isoniazid - adverse effects
Isoniazid - pharmacokinetics
Liver-Specific Organic Anion Transporter 1 - genetics
Male
Outcome Assessment, Health Care
Pharmacogenomic Variants - genetics
Polymorphism, Single Nucleotide
Pregnane X Receptor - genetics
Rifampin - adverse effects
Rifampin - pharmacokinetics
Tuberculosis - drug therapy
Tuberculosis - epidemiology
Tuberculosis - genetics
Uganda - epidemiology
Uganda
ISSN:1532-6535, 1532-6535
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Shrnutí:Unsatisfactory treatment outcomes have been reported in patients coinfected with HIV/tuberculosis (TB). The 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 was performed. The impact of SNPs on antitubercular drug exposure, adverse events, and treatment outcomes was evaluated in patients coinfected with HIV/TB receiving treatments for both conditions. In 221 participants, N-acetyltransferase 2 (NAT2; rs1799930), solute carrier organic anion transporter family member 1B1 (SLCO1B1; rs4149032), and pregnane X receptor (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 patients coinfected with HIV/TB, genetic variants in PXR, SLCO1B1, and NAT2 were moderately associated with isoniazid exposure, whereas PXR 63396TT carriers showed worse outcomes.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1532-6535
1532-6535
DOI:10.1002/cpt.1403