Interactions between antiretroviral agents and those used to treat tuberculosis

PURPOSES OF REVIEW: Metabolic features of protease inhibitors, nonnucleoside reverse transcriptase inhibitors and rifamycins are known to significantly affect the possibility of coadministration of these compounds in HIV/tuberculosis dual infected subjects. In this review recent findings of drug-drug interactions between antiretroviral and antituberculous agents will be discussed.

While protease inhibitors were confirmed to be not compatible with rifampin-containing anti-tuberculosis regimens, in the last year promising data were obtained for existing nonnucleoside reverse transcriptase inhibitors. Nevirapine, particularly, was shown to be safe and effective at standard dosing when associated with rifampin in Asian and African populations, suggesting a pharmacogenetics-based interindividual variability of interaction. On the other hand, although the interaction profile of new antiretrovirals, such as integrase inhibitors, entry inhibitors and most recent nonnucleoside reverse transcriptase inhibitors, has not yet been fully investigated, potential clinical problems of compatibility with rifamycins could be anticipated.

Rifampin-containing antituberculous regimens seem compatible with nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapies, although the need for dose adjustments of the latter probably varies on individual basis. Pharmacogenetics studies aimed to define a possible strategy of posological individualization are warranted, especially for developing countries where nonnucleoside reverse transcriptase inhibitors s are the main antiretroviral option. The newly marketed drugs and drugs under development in both anti-HIV and anti-tuberculosis settings seem not to be devoid of these pharmacological interactions.