Nutritional supplementation increases rifampin exposure among tuberculosis patients coinfected with HIV.
Nutritional supplementation to tuberculosis (TB) patients has been associated with increased weight and reduced mortality, but its effect on the pharmacokinetics of first-line anti-TB drugs is unknown. A cohort of 100 TB patients (58 men; median age, 35 [interquartile range {IQR}, 29 to 40] years, and median body mass index [BMI], 18.8 [17.3 to 19.9] kg/m(2)) were randomized to receive nutritional supplementation during the intensive phase of TB treatment. Rifampin plasma concentrations were determined after 1 week and 2 months of treatment. The effects of nutritional supplementation, HIV, time on treatment, body weight, and SLCO1B1 rs4149032 genotype were examined using a population pharmacokinetic model. The model adjusted for body size via allometric scaling, accounted for clearance autoinduction, and detected an increase in bioavailability (+14%) for the patients in the continuation phase. HIV coinfection in patients not receiving the supplementation was found to decrease bioavailability by 21.8%, with a median maximum concentration of drug in serum (Cmax) and area under the concentration-time curve from 0 to 24 h (AUC0-24) of 5.6 μg/ml and 28.6 μg · h/ml, respectively. HIV-coinfected patients on nutritional supplementation achieved higher Cmax and AUC0-24 values of 6.4 μg/ml and 31.6 μg · h/ml, respectively, and only 13.3% bioavailability reduction. No effect of the SLCO1B1 rs4149032 genotype was observed. In conclusion, nutritional supplementation during the first 2 months of TB treatment reduces the decrease in rifampin exposure observed in HIV-coinfected patients but does not affect exposure in HIV-uninfected patients. If confirmed in other studies, the use of defined nutritional supplementation in HIV-coinfected TB patients should be considered in TB control programs. (This study has the controlled trial registration number ISRCTN 16552219.).
Department of Infectious Diseases, Odense University Hospital, Odense, Denmark National Institute for Medical Research, Mwanza Medical Research Centre, Mwanza, Tanzania jkidola@gmail.com.
Kidola
K
Jeremiah
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Paolo
P
Denti
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Emmanuel
E
Chigutsa
Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Daniel
D
Faurholt-Jepsen
National Institute for Medical Research, Mwanza Medical Research Centre, Mwanza, Tanzania.
George
G
PrayGod
National Institute for Medical Research, Muhimbili Research Centre, Dar Es Salaam, Tanzania.
Nyagosya
N
Range
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Sandra
S
Castel
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Lubbe
L
Wiesner
Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
Christian Munch
CM
Hagen
Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
Michael
M
Christiansen
National Institute for Medical Research, Mwanza Medical Research Centre, Mwanza, Tanzania.
John
J
Changalucha
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Helen
H
McIlleron
Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Henrik
H
Friis
Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
Aase Bengaard
AB
Andersen
D000328:Adult; D001682:Biological Availability; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D015331:Cohort Studies; D060085:Coinfection; D019587:Dietary Supplements; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012293:Rifampin / Q000493:pharmacokinetics*; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*; D015430:Weight Gain / Q000187:drug effects
D012293:Rifampin