Concentrations of the protease inhibitor indinavir are reduced by over 80% if the first-line anti-TB drug rifampicin is being taken at the same time, even when indinavir is boosted by the addition of a small dose of ritonavir, according to a small Danish study published in the February 1st edition of Clinical Infectious Diseases, which is now available online.
Both indinavir and rifampicin are metabolised using the P450 (CYP) 3A4 enzyme, but rifampicin induces the enzyme's activity, causing a substantial reduction in blood concentrations of indinavir. In comparison, an earlier small study found that it was possible to maintain therapeutic blood concentrations of the protease inhibitor saquinavir during rifampicin therapy if the standard dose of saquinavir was boosted by the addition of 100mg dose of the protease inhibitor ritonavir.
Accordingly, Danish investigators conducted a prospective, open label study to see if therapeutic concentrations of indinavir during rifampicin treatment by adding the 100mg ritonavir booster. The study enrolled six HIV-positive patients, all of whom had an HIV viral load below 20 copies/mL and a median CD4 cell count of 355 cells/mm3. All the patients were taking HAART, and rifampicin was provided for four days at a dose of 300mg daily before the collection of study blood samples.
Individuals enrolled in the study had twelve-hour steady state indinavir concentrations measured. Indinavir was dosed at 800mg twice daily, boosted by a 100mg twice-daily dose of ritonavir.
The investigators originally planned to enroll a total of eight patients, but stopped the study early because of the dramatic decreases in indinavir concentrations observed in the first six patients.
An 87% reduction in steady-state indinavir concentrations was recorded twelve hours after dosing with rifampicin, and the ritonavir concentration was reduced by 94%.
”There is [a] clinically significant interaction between indinavir, ritonavir, and rifampin" conclude the investigators, adding “our results strongly indicate that the administration of rifampin with a combination of indinavir (800mg) and ritonavir (100mg)…could lead to subtherapeutic concentrations of indinavir."
Further information on this website
Rifampicin - overview
Indinavir - overview
Justesen US et al. Parmacokinetic interaction between rifampin and the combination of indinavir and low-dose ritonavir in HIV-infected patients. Clinical Infectious Diseases 38 (on-line edition), 2004.