Pharmacological Interactions Between Rifampicin and Antiretroviral Drugs

Abstract

Coadministration of antituberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis (TB) is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and many antiretroviral drugs is complicated by pharmacokinetic drug-drug interactions. Rifampicin is a very potent enzyme inducer, which can result in subtherapeutic antiretroviral drug concentrations. In addition, TB drugs and antiretroviral drugs have additive (pharmacodynamic) interactions as reflected in overlapping adverse effect profiles. This review provides an overview of the pharmacological interactions between rifampicin-based TB treatment and antiretroviral drugs in adults living in resource-limited settings. Major progress has been made to evaluate the interactions between TB drugs and antiretroviral therapy; however, burning questions remain concerning nevirapine and efavirenz effectiveness during rifampicin-based TB treatment, treatment options for TB-HIV-coinfected patients with nonnucleoside reverse transcriptase inhibitor resistance or intolerance, and exact treatment or dosing schedules for vulnerable patients including children and pregnant women. The current research priorities can be addressed by maximizing the use of already existing data, creating new data by conducting clinical trials and prospective observational studies and to engage a lobby to make currently unavailable drugs available to those most in need.

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

“…In Tanzania various studies have been conducted using both conventional and non-conventional means to characterize the disease and its spread. Some of these studies focus on epidemiology [ 2 – 5 ], diagnostics [ 6 – 9 ], treatment and control [ 2 , 10 – 12 ], strain molecular characterization [ 13 – 16 ], TB-HIV co-infections [ 17 – 20 ], challenges and resource limitation [ 21 ], and more recently, TB cross-species transmission at the human-animal interface [ 22 – 24 ]. In the recent study by our group in Serengeti ecosystem [ 15 ], a strain unassigned to neither of known spoligotypes, but resembling the CAS strain family was identified and tentatively named ‘Serengeti strain’.…”

Disulfiram and Copper Ions Kill Mycobacterium tuberculosis in a Synergistic Manner

“…We present disulfiram both as a promising therapeutic compound and as an excellent example of a new class of compounds harnessing copper ions as an environmental insult to enhance antibacterial activity. 4 , 0.5% glucose, and 0.02% tyloxapol. Hygromycin (50 g/ml), 10% oleic acidalbumin-dextrose-catalase (OADC) (Remel), 1% casamino acids, 24 g/ml pantothenate, or combinations thereof were supplemented as needed.…”

“…Major obstacles to global control efforts include (i) the complete lack of convenient and easy-to-comply-with short-term or single-drug treatment options, (ii) the ability of Mycobacterium tuberculosis to persist in the human host, asymptomatically and undetectably, during and after treatment with a 10% lifetime chance to reactivate eventually (2), (iii) adverse drug interactions in the cotreatment of HIV and M. tuberculosis infections (3,4), (iv) a short supply of first-line drugs (5), and (v) the rise of multidrug-resistant (MDR), extensively drug-resistant (XDR), and even totally drug-resistant (TDR) M. tuberculosis strains (6). Only two new antitubercular drugs, bedaquiline (Sirturo, TMC207) and delamanid (Deltyba, OPC-67683), were approved in recent years for use against MDR-and XDR-TB in the United States and Europe, respectively, with phase III clinical trials still ongoing to elucidate potentially serious side effects that may limit the utility of these drugs (7)(8)(9).…”

Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections

“…The complications from drug-drug interactions for concomitmant therapy of both conditions have been reviewed (Gengiah et al, 2011 ; Regazzi et al, 2014 ; Semvua et al, 2015 ). The first-line TB drug rifampicin (RIF) is a potent inducer of hepatic cytochrome CYP450 system, thus increasing the rate of metabolism of antiretroviral drugs in the liver to result in subtherapeutic antiretroviral drug concentrations (Piscitelli and Gallicano, 2001 ; Semvua et al, 2015 ). Protease inhibitors are known to be substrates of CYP3A4 and therefore could not be coadministered with RIF (Gengiah et al, 2011 ).…”