Delayed Sputum Culture Conversion in Tuberculosis–Human Immunodeficiency Virus–Coinfected Patients With Low Isoniazid and Rifampicin Concentrations

Abstract

Although low antituberculosis drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications for tuberculosis transmission. Clinical Trials Registration: NCT01782950.

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

“…Several studies have recognized the role of underexposure of one or more compounds and the association of this event with unfavorable outcomes, such as slow response or treatment failure. In the same study population, Sekaggya‐Whiltshire and colleagues found a significant association between low concentrations of RIF and INH and delayed culture conversion and concluded that this may have implications for TB transmission. In this pharmacogenetic analysis, we observed that INH exposure (both as AUC 0–4 and C max ) could be predicted by gender and by genetic variants in three genes: NAT2 , SLCO1B1 , and PXR .…”

“…In this prospective observational study, the correlation of anti‐TB drug concentrations and clinical response in individuals infected with HIV with new pulmonary TB was investigated. The study was conducted at the Infectious Diseases Institute, Kampala, Uganda, a center of excellence in HIV care and treatment …”

“…The study was conducted at the Infectious Diseases Institute, Kampala, Uganda, a center of excellence in HIV care and treatment. 7,38 Ethics approval was received from the Joint Clinical and Research Centre Institutional Review Board, the Uganda National Council for Science and Technology, and the National Drug Authority. Written informed consent was obtained from all study participants prior to enrollment, and separate consent was obtained for pharmacogenetics study participation.…”

“…Low serum concentrations of antitubercular drugs are associated with slow response and treatment failure, and they may contribute to the selection of drug‐resistant strains . A recent analysis in patients coinfected with HIV/TB in Uganda showed that patients with low concentrations of rifampicin (RIF) and isoniazid (INH) were less likely to reach sputum culture conversion before the end of TB treatment or by the end of follow‐up (6 months after the completion of treatment) …”

“…6 A recent analy sis in patients co infected with HIV/TB in Uganda showed that patients with low concentrations of rifampicin (RIF) and isoniazid (INH) were less likely to reach sputum culture conversion before the end of TB treatment or by the end of follow-up (6 months after the completion of treatment). 7 Interindividual variability, tissue penetration, and drug-drug interactions are partially explained by genetic variants in genes encoding for drug metabolizing or transporting proteins. Singlenucleotide polymorphisms (SNPs) are the most common genetic variants; they seldom influence protein expression or activity, whereas some genetic variants may affect the risk of developing certain diseases as well as the efficacy and tolerability of several compounds.…”