Low rifampicin concentrations in tuberculosis patients with HIV infection

  • Tanuja Narayansamy Gengiah CAPRISA - Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa
  • Julia Hillary Botha School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
  • Deepak Soowamber CAPRISA - Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa
  • Kogieleum Naidoo CAPRISA - Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa
  • Salim S Abdool Karim CAPRISA - Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa
Keywords: drug interactions, pharmacogenetics, TB recurrence, co-infection

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) µg/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) µg/mL in the heterozygous and 3.4 (2.7-4.7) µg/mL 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 μg/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.

Author Biographies

Tanuja Narayansamy Gengiah, CAPRISA - Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa
Head of Pharmacy
Julia Hillary Botha, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Professor
Salim S Abdool Karim, CAPRISA - Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa
Professor
Published
2014-08-13
How to Cite
1.
Gengiah TN, Botha JH, Soowamber D, Naidoo K, Abdool Karim SS (2014) Low rifampicin concentrations in tuberculosis patients with HIV infection. J Infect Dev Ctries 8:987-993. doi: 10.3855/jidc.4696
Section
Original Articles