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Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis

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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.

 

 
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