Systemic exposure to rifampicin in patients with tuberculosis and advanced HIV disease during highly active antiretroviral therapy in Burkina Faso.
OBJECTIVE
Low plasma concentrations of rifampicin, an essential antituberculosis drug, have been reported particularly among HIV co-infected persons. In a prospective, longitudinal study we measured rifampicin systemic exposure at different timepoints during highly active antiretroviral therapy (HAART).


METHODS
From May 2006 to April 2007, 16 tuberculosis (TB)/HIV co-infected patients were enrolled in Ouagadougou, Burkina Faso. All patients received fixed dose combinations of rifampicin, isoniazid, pyrazinamide and ethambutol under direct observation and HAART, consisting of a fixed dose combination of stavudine, lamivudine and nevirapine. Rifampicin concentrations during the dosing interval were determined by HPLC at three different timepoints: (i) after 2 weeks of TB therapy and before starting HIV therapy (T0); (ii) after 4 weeks of combined therapy (T1); and (iii) after 10 weeks of combined therapy (T2).


RESULTS
The median values of the area under the curve (AUC(0-24)) of rifampicin increased by 39% at T1 (15.69 μg · h/mL; P = 0.01) and by 83% at T2 (20.65 μg · h/mL; P = 0.001) compared with T0 (11.28 μg · h/mL). Similar variations were observed for the median C(max) at T0 (2.24 μg/mL) compared with T2 (2.83 μg/mL; P = 0.003). However, none of the subjects had C(max) levels >8 μg/mL at either T0 or T2.


CONCLUSIONS
Rifampicin systemic exposure increased during combined TB and HIV therapy, possibly due to increased drug absorption or decreased oral clearance, but remained invariably low in this population. Studies to define the C(max) rifampicin concentrations, which are associated with a significantly increased risk of treatment failure, are urgently warranted.
National Tuberculosis Program, Ministry of Health, Ouagadougou,  Burkina Faso.
Nuccia
N
Saleri
Sary Mathurin
SM
Dembélé
Paola
P
Villani
Anna Cristina C
AC
Carvalho
Maria
M
Cusato
Victor
V
Bonkoungou
Rachel
R
Nacanabo
Seni
S
Kouanda
Mario
M
Comelli
Mario
M
Regazzi
Alberto
A
Matteelli
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002050:Burkina Faso; D002851:Chromatography, High Pressure Liquid; D004977:Ethambutol / Q000008:administration & dosage; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011718:Pyrazinamide / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*
D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin