Initiating antiretrovirals during tuberculosis treatment: a drug safety review

Abstract

Introduction: Integrating HIV and tuberculosis (TB) treatment can reduce mortality substantially. Practical barriers to treatment integration still exist and include safety concerns related to concomitant drug use because of drug interactions and additive toxicities. Altered therapeutic concentrations may influence the chances of treatment success or toxicity.

Areas covered: The available data on drug-drug interactions between the rifamycin class of anti-mycobacterials and the non-nucleoside reverse transcriptase inhibitor and the protease inhibitor classes of antiretrovirals are discussed with recommendations for integrated use. Additive drug toxicities, the impact of immune reconstitution inflammatory syndrome (IRIS) and the latest data on survival benefits of integrating treatment are elucidated.

Expert opinion: Deferring treatment of HIV to avoid drug interactions with TB treatment or the occurrence of IRIS is not necessary. In the integrated management of TB-HIV co-infection, rational drug combinations aimed at reducing toxicities while effecting TB cure and suppressing HIV viral load are possible.

Figure 1

Drug interactions following oral administration may be mediated at four stages of disposition [15]

Figure 1

Possible metabolic drug interactions and the cytochrome (CYP) P450 system