Select antiretroviral and non-rifamycin-based antituberculosis drug overlapping toxicities and potential adverse drug-drug interactions

Potential overlapping toxicities and drug–drug interactions	Antiretroviral drugs	Non-rifamycin TB drugs
Arrhythmias, QT interval prolongation	Lopinavir/ritonavir, efavirenz Note PR interval prolongation* with atazanavir, lopinavir/ritonavir	Fluoroquinolones^¶, bedaquiline, delamanid, clofazimine
Hepatic cytochrome P450 enzyme system metabolism	Induce CYP P450 metabolism: efavirenz, etravirine, and nevirapine Impede CYP P450 metabolism: protease inhibitors, cobicistat	Bedaquiline, delamanid
Nephrotoxicity	Tenofovir,^Δ atazanavir Isolated creatinine elevation^◊: cobicistat, dolutegravir	Aminoglycosides, capreomycin
Mental health changes (depression, psychosis, dizziness, etc.)	Efavirenz, rilpivirine; dolutegravir, elvitegravir, raltegravir	Cycloserine, isoniazid, ethionamide, fluoroquinolones†
Peripheral neuropathy	Stavudine, zidovudine	Aminoglycosides, capreomycin, linezolid, isoniazid, ethionamide, cycloserine, fluoroquinolones^¶
Hepatotoxicity	Lactic acidosis with hepatic steatosis higher risk with stavudine, zidovudine; protease inhibitors; nevirapine (higher risk in patients with elevated CD4 cell counts); less common with efavirenz, etravirine and rilpivirine; maraviroc Indirect hyperbilirubinemia^§: atazanavir	Isoniazid, pyrazinamide, ethionamide, p-aminosalicylic acid, clofazimine
Skin rash	Nevirapine (higher risk in patients with elevated CD4 cell counts), efavirenz, etravirine, rilpivirine Any protease inhibitor (especially those containing sulfonamide moiety: eg, darunavir); abacavir (hypersensitive reaction a risk in patient who are HLA-B5701 positive); raltegravir	All TB drugs Note skin pigmentation with clofazimine use Thioacetazone should be avoided in people with HIV, because of an elevated risk of a severe adverse skin reaction
Dysglycemia	Lopinavir/ritonavir, ritonavir, stavudine, zidovudine	Ethionamide, p-aminosalicylic acid, fluoroquinolones, linezolid
Myelosuppression/cytopenias	Zidovudine	Linezolid
Lactic acidosis	Stavudine, zidovudine	Linezolid

Saquinavir, indinavir, fosamprenavir, tipranavir, and didanosine are older antiretroviral drugs that are rarely used in the United States. They do have many of the adverse interactions listed above with select TB drugs, and clinicians considering the use of these agents should therefore consult with an expert.

TB: tuberculosis.
* Use with caution in patients with underlying cardiac dysrhythmia.
¶ Fluoroquinolones include ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin.
Δ Tenofovir alafenamide is a prodrug of tenofovir and U.S. Food and Drug Administration approved in 2015. It is associated with decreased incidence of osteoporosis and nephrotoxicity compared with tenofovir disoproxil fumarate through achieving higher intracellular drug concentrations with a lower dose administered.
◊ Increases in serum creatinine via decrease in renal tubular creatinine excretion are commonly seen with cobicistat and dolutegravir usage. This is not a toxicity.
§ Indirect hyperbilirubinemia is expected with atazanavir and indinavir. This is not a toxicity.

Reprinted with permission of the American Thoracic Society. Copyright © 2019 American Thoracic Society. From: Nahid P, Mase SR, Migliori GB, et al. Treatment of drug-resistant tuberculosis: an official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019; 200:e93. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.

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Select antiretroviral and non-rifamycin-based antituberculosis drug overlapping toxicities and potential adverse drug-drug interactions