Treatment Options for Patients with HIV Infection and Drug-Susceptible Pulmonary TB

A.II DOT and other strategies that promote adherence to therapy should be used for all patients with HIV-related TB.

A.II For patients who are receiving therapy with protease inhibitors or NNRTIs, the initial phase of a 6-month TB regimen consists of isoniazid, rifabutin, pyrazinamide, and ethambutol. These drugs are administered a) daily for 8 weeks or b) daily for at least the first 2 weeks, followed by twice-a-week dosing for 6 weeks, to complete the 2-month induction phase. The second phase of treatment consists of isoniazid and rifabutin administered daily or twice a week for 4 months (see Six-month RFB-based therapy in Table 1A of Appendix).

B.II For patients for whom the use of rifamycins is limited or contraindicated for any reason (e.g., intolerance to rifamycins, patient/clinician decision not to combine antiretroviral therapy with rifabutin), the initial phase of a 9-month TB regimen consists of isoniazid, streptomycin,* pyrazinamide, and ethambutol administered a) daily for 8 weeks or b) daily for at least the first 2 weeks, followed by twice-a-week dosing for 6 weeks, to complete the 2-month induction phase. The second phase of treatment consists of isoniazid, streptomycin,* and pyrazinamide administered 2-3 times a week for 7 months (see Nine-month SM-based therapy in Table 1A of Appendix).

A.I For patients who are not candidates for antiretroviral therapy, or for those patients for whom a decision is made not to combine the initiation of antiretroviral therapy with TB therapy, the preferred option continues to be a 6-month regimen that consists of isoniazid, rifampin, pyrazinamide, and ethambutol (or streptomycin). These drugs are administered a) daily for 8 weeks or b) daily for at least the first 2 weeks, followed by 2-3-times-per-week dosing for 6 weeks, to complete the 2-month induction phase. The second phase of treatment consists of a) isoniazid and rifampin administered daily or 2-3 times a week for 4 months. Isoniazid, rifampin,pyrazinamide, and ethambutol (or streptomycin) also can be administered three times a week for 6 months (see Six-month RIF-based therapy in Table 1A of Appendix).

D.II TB regimens consisting of isoniazid, ethambutol, and pyrazinamide (i.e., three-drug regimens that do not contain a rifamycin, an aminoglycoside [e.g., streptomycin, amikacin, kanamycin], or capreomycin) should generally not be used for the treatment of patients with HIV-related TB; if these regimens are used for the treatment of TB, the minimum duration of therapy should be 18 months (or 12 months after documented culture conversion).

A.II Pyridoxine (vitamin B6) (25-50 mg daily or 50-100 mg twice weekly) should be administered to all HIV-infected patients who are undergoing TB treatment with isoniazid, to reduce the occurrence of isoniazid-induced side effects in the central and peripheral nervous system.

E.II Because CDC's most recent recommendations for the use of antiretroviral therapy strongly advise against interruptions of therapy,** and because alternative TB treatments that do not contain rifampin are available, previous antituberculosis therapy options that involved stopping protease inhibitor therapy to allow the use of rifampin (Option I and Option II [ 3 ])are no longer recommended.

Medications and Doses for Treatment of TB

Duration of TB Treatment
A.II The minimum duration of short-course rifabutin-containing TB treatment regimens is 6 months, to complete a) at least 180 doses (one dose per day for 6 months) or b) 14 induction doses (one dose per day for 2 weeks)followed by 12 induction doses (two doses per week for 6 weeks) plus 36 continuation doses (two doses per week for 18 weeks) (see Six-month RFB-based therapy in Table 1A of Appendix).
A.II The minimum duration of short-course rifampin-containing TB treatment regimens is 6 months, to complete a) at least 180 doses (one dose per day for 6 months) or b) 14 induction doses (one dose per day for 2 weeks) followed by 12-18 induction doses (two to three doses per week for 6 weeks) plus 36-54 continuation doses (two to three doses per week for 18 weeks) (see Six-month RIF-based therapy in Table 1A of Appendix).
A.II Three-times-per-week rifampin regimens should consist of at least 78 doses administered over 26 weeks.***
A.II The final decision on the duration of therapy should consider the patient's response to treatment. For patients with delayed response to treatment(see Box 2), the duration of rifamycin-based regimens should be prolonged from 6 months to 9 months (or to 4 months after culture conversion is documented).
A.II The minimum duration of nonrifamycin, streptomycin-based TB treatment regimens is 9 months, to complete a) at least 60 induction doses (one dose per day for 2 months) or b) 14 induction doses (one dose per day for 2 weeks) followed by 12-18 induction doses (two to three doses per week for 6 weeks) plus either 60 continuation doses (two doses per week for 30 weeks) or 90 continuation doses (three doses per week for 30 weeks).
A.II When making the final decision on the duration of therapy, clinicians should consider the patient's response to treatment. For patients with delayed response to treatment (see Box 2), the duration of streptomycin-based regimens should be prolonged from 9 months to 12 months (or to 6 months after culture conversion is documented).
A.III Interruptions in therapy because of drug toxicity or other reasons should be taken into consideration when calculating the end-of-therapy date for individual patients. Completion of therapy is based on total number of medication doses administered and not on duration of therapy alone.
A.III Reinstitution of therapy for patients with interrupted TB therapy might require a continuation of the regimen originally prescribed (as long as needed to complete the recommended duration of the particular regimen)or a complete renewal of the regimen. In either situation, when therapy is resumed after an interruption of => 2 months, sputum samples (or other clinical samples as appropriate) should be taken for smear, culture, and drug-susceptibility testing.

*Every effort should be made to continue administering streptomycin for the total duration of treatment or for at least 4 months after culture conversion (approximately 6-7 months from the start of treatment). Some experts suggest that in situations in which streptomycin is not included in the regimen for all of the recommended 9 months, ethambutol should be added to the regimen to replace streptomycin, and the duration of treatment should be prolonged from 9 months to 12 months. Alternatives to streptomycin are the injectable drugs amikacin,kanamycin, and capreomycin.

**To minimize the emergence of drug-resistant HIV strains, if any antiretroviral medication must be temporarily discontinued for any reason, clinicians and patients should be aware of the theoretical advantage of stopping all antiretroviral agents simultaneously, rather than continuing the administration of one or two of these agents alone (4).

***Three-times-per-week rifabutin regimens, used in combination with antiretroviral therapy, have not been studied.

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