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Low rifampicin concentrations in tuberculosis patients with HIV infection.
- Source :
-
Journal of Infection in Developing Countries . Aug2014, Vol. 8 Issue 8, p987-993. 7p. - Publication Year :
- 2014
-
Abstract
- Introduction: The efficacy of tuberculosis (TB) treatment in Human Immunodeficiency Syndrome (HIV) co-infected patients may be compromised by genetic and pharmacokinetic variation in drug disposition. Rifampicin is a critical component of TB treatment. We investigated the influence of drug transporter gene polymorphisms on rifampicin concentrations in TB-HIV co-infected patients in Durban, South Africa. Methodology: Rifampicin concentrations were measured 2.5 hours post-dose (approximated peak, C2.5hr) in patients receiving either 450mg or 600mg rifampicin, randomized to either integrated or sequential antiretroviral treatment. Patients were genotyped for SLCO1B1 (rs4149032) polymorphisms. A mixed effects regression model was fitted to assess the influence of various factors on rifampicin concentrations. TB recurrence rates were also estimated. Results: In 57 patients, median (IQR) C2.5hr was 3.6 (2.8-5.0) ng/mL. Polymorphism frequency in the SLCO1B1 (rs4149032) drug transporter gene was high (0.76) and was associated with low median rifampicin C2 .5hr, 3.7 (2.8-5.0) ng/inL in the heterozygous and 3.4 (2.7-4.7) ng/inL in the homozygous variant carriers. Concentrations were also low in males (p < 0.0001) and those with low haemoglobin (p = 0.02). Although reinfection could not be distinguished from reactivation for the 43 patients followed post trial, the incidence of TB recurrence was 7.1 per 100 person-years. Of the eight patients in whom TB recurred, seven had the polymorphism. Conclusion: Approximated peak rifampicin concentrations were well below the recommended target range of 8 to 24 |xg/mL in this patient population with its high frequency of the SLCO1B1 (rs4149032) polymorphism. Increased rifampicin dosage may be warranted in African, HIV- TB co-infected patients. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20366590
- Volume :
- 8
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Journal of Infection in Developing Countries
- Publication Type :
- Academic Journal
- Accession number :
- 97480881
- Full Text :
- https://doi.org/10.3855/jidc.4696