Low isoniazid and rifampicin concentrations in TB/HIV co-infected patients in Uganda.
BACKGROUND
There is limited data available on exposure to anti-tuberculosis (TB) drugs in this region. Peloquin has described reference ranges [1] however some studies have demonstrated that patients actually achieve concentrations below these ranges [2]. There is limited data about exposure to anti-TB drugs in the HIV/TB 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 carried out in the TB/HIV integrated clinic at the Infectious Diseases Institute in Kampala, Uganda. Sputum culture and microscopy was done for all patients. We performed pharmacokinetic blood sampling of anti-TB drugs for 1 hour, 2 hours and 4 hours post dose at 2 weeks, 8 weeks and 24 weeks after initiation of anti-TB treatment using ultraviolet high-performance liquid chromatography (UV-HPLC). We described 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, of which 52% were male with a median BMI of 19 kg/m(2) and a median CD4 cell count of 142 cells/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 IQR of H and R.


CONCLUSIONS
We observed lower concentrations of isoniazid and rifampicin in our study population of HIV/TB co-infected patients. The implications of these findings are not yet clear. We therefore need to correlate our findings with the response to TB treatment.
Infectious Diseases Institute, Research, Kampala, Uganda.
Christine Sekaggya
CS
Wiltshire
Infectious Diseases Institute, Research, Kampala, Uganda.
Mohammed
M
Lamorde
Infectious Disease and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland.
Alexandra
A
Scherrer
Infectious Diseases Institute, Research, Kampala, Uganda.
Joseph
J
Musaazi
Clinical Pharmacology and Toxicology, University Hospital of Zurich, Zurich, Switzerland.
Natascia
N
Corti
Infectious Diseases Institute, Research, Kampala, Uganda.
Buzibye
B
Allan
Infectious Diseases Institute, Research, Kampala, Uganda.
Rita
R
Nakijoba
Infectious Diseases Institute, Research, Kampala, Uganda.
Damalie
D
Nalwanga
Infectious Disease and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland.
Lars
L
Henning
Infectious Diseases Institute, Research, Kampala, Uganda.
Amrei
A
Von Braun
Infectious Diseases Institute, Research, Kampala, Uganda.
Solome
S
Okware
Infectious Diseases Institute, Research, Kampala, Uganda.
Barbara
B
Castelnuovo
Infectious Diseases Institute, Research, Kampala, Uganda.
Andrew
A
Kambugu
Infectious Disease and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland.
Jan
J
Fehr