Authors: Sekaggya C (1), Lamorde M (1), Scherrer A.U (2), Musaazi J (1), Corti N (2), Buzibye A (1), Nakijoba R (1), Nalwanga D (1), Henning L (2), von Braun A (1), Okware S (1), Castelnuovo B (1), Kambugu A (1), Fehr J (2).

1) Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda

2) Division of Infectious Diseases and Infection Control, University Hospital of Zurich, University of Zurich, Switzerland

Aims: There is limited data on exposure to anti-tuberculosis (TB) drugs in this region. Charles Peloquin et al (2002) have described reference ranges; however some studies demonstrated that patients actually achieve concentrations below these ranges. There is limited data about exposure to anti-TB drugs in the TB/HIV co-infected population in Sub-Saharan Africa. Our objective is to describe the concentration of anti-TB drug levels in a well characterized prospective cohort of adult patients starting treatment for pulmonary TB.

Methods: This study is an ongoing study being carried out in the TB/HIV integrated clinic at the Infectious Diseases Institute (IDI) in Kampala, Uganda. Sputum culture and microscopy was done for all patients. Pharmacokinetic blood sampling of anti-TB drugs was done 1 hour, 2 hours and 4 hours post dose 2 weeks, 8 weeks and 24 weeks after initiation of anti-TB treatment using ultra violet high – performance liquid chromatography (UV-HPLC) . We describe the maximum concentration (Cmax) of isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) and compare them with the values observed by Peloquin et al referenced in other studies.

Results: We started 113 HIV infected adults on a fixed dose combination of HREZ. The median age of our population was 33 years. 52% were male with a median BMI of 19kg/m2 and a median CD4 cell count of 142cells/µL. In 90% of the participants, the diagnosis of TB was based on microscopy and/or cultures. The boxplot graph shows the median Cmax and interquartile range (IQR) of H and R. Levels of H were found to be below the reference ranges (3-6µg/mL) in 54/77(70.1%), 38/59(64.4%) and 15/24(62.5%) participants at weeks 2, 8 and 24. R levels were also found to be below the reference ranges (8-24ug/mL) in 41/66(62.1%), 26/48(54.2%) and 8/10(8%) participants at weeks 2, 8, and 24 respectively. The mean Cmax of E and Z were within the reference range at week 2 and 8; mean Cmax of 3.2±SD2.1ug/mL and 4.0±SD3.1ug/mL for E and 41.6±SD13.1ug/mL and 42.6±SD16.4ug/mL for Z.

Conclusion: We observed lower concentrations of isoniazid and rifampicin in our study population of TB/HIV co-infected patients. The implications of these findings are not yet clear. We therefore plan to correlate our findings with the response to TB treatment.

Maximum drug concentration in comparison to reference ranges