Table 5

Approaches to cotreatment for HIV-infected patients with rifampicin-susceptible tuberculosis
Combined regimens Treatment recommendations Drug-drug interactions
Efavirenz + rifampicin-based TB treatment No dose adjustments TDF + 3TC/FTC + EFV (WHO-recommended optimum regimen) AZT + 3TC + EFV (alternative WHO regimen) Rifampicin induces CYP2B6 but inhibition of CYP2A6 by isoniazid might account for increased efavirenz concentrations during TB treatment in those patients with slow CYP2B6 metabolizer genotype
Nevirapine + rifampicin-based TB treatment Omit 14 day lead-in phase of once daily dose of NVP TDF + 3TC/FTC + NVP (alternative WHO regimen) AZT + 3TC + NVP (alternative WHO regimen) Rifampicin induces CYP2B6 and CYP3A4. Although TB treatment reduces nevirapine concentrations, toxicity concerns curtail increasing the dose and outcomes are acceptable (but inferior to EFV) on standard doses.
Lopinavir/ritonavir + rifampicin-based TB treatment Double dose lopinavir/ritonavir (800/200 mg 12 hourly) Or superboost lopinavir (lopinavir/ritonavir 400/400 mg 12 hourly) Monitor alanine transaminase (ALT) closely. Rifampicin induces CYP3A4, p-glycoprotein and OATP1B1. Ritonavir counteracts this effect and adjusted doses of ritonavir or lopinavir/ritonavir are used to compensate, but lopinavir concentrations may be more variable. Increased risk of hepatotoxicity, and gastrointestinal side effects.
PI/ritonavir + rifabutin-based TB treatment Reduce rifabutin dose to 150 mg daily or thrice weekly. Monitor closely for rifabutin toxicity. Ritonavir-boosted PIs markedly increase rifabutin concentrations and reduce its clearance necessitating reduction in the dose of rifabutin by 50% to 75%. Toxicity (neutropenia, uveitis, hepatoxicity, rash, gastrointestinal symptoms) and suboptimal rifamycin exposures with reduced dose are concerns.
Triple nucleoside/tide regimen + rifampicin-based TB treatment No dose adjustments. A triple nucleoside/tide regimen should include tenofovir or abacavir. Monitor viral load. Triple nucleoside/tide regimens may perform adequately in patients with viral suppression who have not failed a first line regimen, and provide alternative ART regimens in patients with contraindications to efavirenz or nevirapine, wehre other options are unavailable. TB treatment has minimal effect on tenofovir concentrations. Although rifampicin induces the enzymes responsible for glucuronidation of abacavir and zidovudine, this effect is not thought to be clinically important.

3TC 2′,3′-dideoxy-3′-thiacytidine, ART antiretroviral therapy, CYP cytochrome P450, EFV efavirenz, FTC emtricitabine, OATP organic anion-transporting polypeptide, NNRTI non-nucleoside reverse transcriptase inhibitor, NVP nevirapine, PI protease inhibitor, TB tuberculosis, TDF tenofovir, WHO World Health Organization.

Lawn et al.

Lawn et al. BMC Medicine 2013 11:253   doi:10.1186/1741-7015-11-253

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