Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis
Table 1a. Recommendations for regimens for the concomitant treatment of tuberculosis and HIV infection in adults
Combined regimen for treatment of HIV and tuberculosis | PK effect of the rifamycin on ART | Tolerability / toxicity | Antiviral activity when used with rifamycin | Recommendation (comments) |
Efavirenz-based antiretroviral therapy (ART) * with rifampin-containing tuberculosis treatment | Well-characterized, modest decrease in concentrations in some patients | Low rates of discontinuation | Excellent | Preferred (efavirenz should not be used during the first trimester of pregnancy) |
PI-based ART * with rifabutin-containing tuberculosis treatment | Little effect of rifabutin on PI concentrations, but marked increases in rifabutin concentrations | Low rates of discontinuation (if rifabutin is appropriately dose-reduced) | Favorable, though published clinical experience is not extensive | Preferred for patients unable to take efavirenz † (caution to ensure patients who discontinue PIs do not continue to receive reduced rifabutin dose) |
Nevirapine-based ART with rifampin-containing tuberculosis treatment | Moderate decrease in concentrations | Concern about hepatotoxicity when used with isoniazid, rifampin and pyrazinamide | Suboptimal when nevirapine is initiated using once-daily dosing; largely favorable when nevirapine is given twice-daily throughout co-treatment | Alternative for patients who cannot take efavirenz, though efavirenz is preferred (nevirapine should not be initiated among women with CD4>250 or men with CD4>400 cells/µL). Viral load monitoring is recommended. |
Raltegravir-based ART* with rifampin-containing tuberculosis treatment | Significant decrease in concentrations with standard dosing | Limited experience | Limited published clinical experience | Alternative at higher doses for patients who cannot take efavirenz and who have baseline viral load <100,000 copies/mL |
Zidovudine / lamivudine / abacavir / tenofovir with rifampin-containing tuberculosis treatment | 50% decrease in zidovudine, possible effect on abacavir not evaluated | Anemia | No published clinical experience, but this combination is less effective than efavirenz- or atazanavir-based regimens in persons not taking rifampin | Alternative for patients who cannot take efavirenz or NVP and if rifabutin not available |
Zidovudine / lamivudine / tenofovir with rifampin-containing tuberculosis treatment | 50% decrease in zidovudine, no other effects predicted | Anemia | Favorable, but not evaluated in a randomized trial | Alternative for patients who cannot take efavirenz and abacavir and if rifabutin not available |
Zidovudine / lamivudine / abacavir with rifampin-containing tuberculosis treatment | 50% decrease in zidovudine, possible effect on abacavir not evaluated | Anemia | Early favorable experience, but this combination is less effective than efavirenz- or nevirapine-based regimens in persons not taking rifampin | Alternative for patients who cannot take efavirenz and tenofovir and if rifabutin not available |
Super-boosted‡ lopinavir-based ART or double-dose lopinavir/ritonavir based ART with rifampin-containing tuberculosis treatment | Modest decrease in concentrations | Hepatitis | Early favorable experience of super-boosting among young children and double-dose among adults already on antiretroviral drugs at the time of rifampin initiation | Alternative if rifabutin not available; double dose an option among adults already taking lopinavir-based ART and virologically suppressed at the time of tuberculosis treatment initiation; super boosting has not been adequately tested in adults but may be effective |
* with 2 nucleoside analogues
† includes patients with NNRTI-resistant HIV, those unable to tolerate efavirenz, women during the first trimester of pregnancy
‡ Super-boosting of lopinavir is achieved by giving lopinavir 400 mg together with 400 mg ritonavir twice daily. Double-dose lopinavir/ritonavir is lopinavir 800 mg plus ritonavir 200 mg twice daily.