Table 1.

Approaches to cotreatment for HIV-infected patients with rifampicin-susceptible tuberculosis

Combined regimes	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 d 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 every12 h) or superboost lopinavir (lopinavir/ritonavir 400/400 mg every 12 h). Monitor alanine transaminase (ALT) closely.	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 rifamyin exposures with reduced dose are concerns.
Triple nucleoside/nucleotide regime + rifampicin-based TB treatment	No dose adjustments. A triple nucleoside/nucleotide regimen should include tenofovir or abacavir. Monitor viral load.	Triple nucleoside/nucleotide 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, in which 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.

Data adapted from Lawn et al. 2013.

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