Drug–drug interactions and tolerance in combining antituberculosis and antiretroviral therapy

Abstract

Worldwide, tuberculosis (TB) is one of the most important infectious diseases in subjects with HIV infection. Although effective therapy is available for both conditions, there are major problems in the concurrent treatment of HIV and TB co-infection. In this article the knowledge available on drug-drug interactions between anti-HIV and anti-TB compounds is analysed, particularly with regard to pharmacological interactions secondary to interference with cytochrome P450 enzymes. Within the same setting, facts and possible interpretations of the problems encountered in terms of tolerance and safety of the concurrent treatment of TB and HIV are also reviewed. Current guidelines, as well as additional possible strategies to be adopted in this particular co-morbidity setting are discussed.

The Influence of Antiretroviral and Antituberculosis Agents on the Biochemical and Histopathological Indices of Liver Function in Rats

“…Nucleoside reverse-transcriptase inhibitors (NRTIs), like d4T, are metabolized by glucuronidation pathway and don't have any influence on CYP450 [20]. Concerning the antituberculosis drugs, RMP is a potent inducer of CYP3A isoenzyme, as well as of other P450 isoforms, more potent than rifapentine and rifabutin [21]. PZA can induce CYP2E1 [22].…”

Pharmacokinetic Interaction Study of Ritonavir-Boosted Saquinavir in Combination with Rifabutin in Healthy Subjects

“…The rifamycins, including rifampin and rifabutin, are mainstays in the treatment of tuberculosis, but because they induce CYP3A4, they lower the exposure of coadministered protease inhibitors such as saquinavir (7,10). This complication can in principle be obviated by regimens involving the concomitant administration of ritonavir, an inhibitor of CYP3A4.…”

“…Not only is there an increased risk of reactivation of latent tuberculosis infections in HIV-coinfected patients, but the progression of new tuberculosis infections is also accelerated (7,10). The antimycobacterial agent rifabutin is being used for the prevention and treatment of active Mycobacterium tuberculosis infection in patients with advanced HIV infection in combination with other agents (7).…”

Moxifloxacin for the treatment of HIV-associated tuberculosis in patients with contraindications or intolerance to rifamycins

“…2 Its introduction in clinical practice allowed to significantly shorten the duration of antituberculous therapy. 1,2,7 Use of rifampicin in patients with HIV infection can be hampered by additive toxicity and pharmacological interactions with antiretrovirals. 1,2,7 Rifampicin is a potent inducer of CYP3A4, and as a consequence its administration with any PIs is contraindicated as it determines a marked decrease in PIs plasma exposure through enhancement of their metabolism by the CYP3A4 isoenzyme.…”

“…1 In dually HIVeTB-infected patients, both rifampicin, the so far undisputed cornerstone of antituberculous treatment, 2 and rifabutin, the only suggested alternative to rifampicin, 2 have been repeatedly found to be associated to an increased rate of adverse effects and clinically significant interactions with antiretrovirals. 1,2 Although in current practice the priority is that of administering rifampicin with exclusion of the most interacting antiretrovirals (e.g. protease inhibitors, PIs), there are clinical circumstances in which rifamycins cannot be used.…”