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Persons using assistive technology might not be able to fully access information in this file. For assistance, please send e-mail to: mmwrq@cdc.gov. Type 508 Accommodation and the title of the report in the subject line of e-mail. Appendix - Recommended Treatment Options for Persons with Human Immunodeficiency Virus-Related Tuberculosis Infection and Disease(Table_1A) Table 1A. Treatment regimens for human immunodeficiency virus (HIV)-related tuberculosis (TB) (Table_2A) Table 2A. Antituberculosis medcations: doses, toxicities, and monitoring requirements. (Table_3A) Table 3A. Tuberculosis (TB) preventive therapy regimens for adults with human immunodeficiency virus (HIV) infection Table_1A Note: To print large tables and graphs users may have to change their printer settings to landscape and use a small font size. Table 1A. Treatment regimens for human immunodeficiency virus (HIV)-related tuberculosis (TB) =================================================================================================================================================================== Induction Phase Continuation Phase ----------------------------- ----------------------------- Rating Drugs Interval and Duration Drugs Interval and Duration Considerations for HIV Therapy Comments ------------------------------------------------------------------------------------------------------------------------------------------------------------------- Six-month RFB-based therapy (may be prolonged* to 9 months) ------------------------------------------------------------------------------------------------------------------------------------------------------------------- A.II INH Daily for 2 months INH Daily or 2 times/week RFB should not be used If the patient also is taking RFB (8 weeks) RBF for 4 months (18 weeks) concurrently with ritonavir, indinavir, nelfinavir, or PZA+ hard-gel saquinavir (Invirase), amprenavir, the daily dose of RFB or delavirdine. is decreased from 300mg to 150mg. The twice-weekly dose of RFB (300mg) remains unchanged if the patient is also taking these protease inhibitors. or or A 20%-25% increase in the dose of protease inhibitors or NNRTIs might be necessary. INH Daily for 2 weeks and INH 2 times/week for The patient should be monitored If the patient also is taking RFB then 2 times/week for RFB 4 months (18 weeks) carefully for RFB drug toxicity efavirenz, the daily or twice (arthalgia, uveitis,leukopenia) weekly dose of RFB is increased if RFB is used concurrently from 300mg to 450 mg. with protease inhibitors or NNRTIs. Evidence of decreased Three times a week antiretroviral drug activity administration of RFB used in should be assessed combination with antiretroviral periodically with HIV RNA therapy has not been studied. levels. No contraindication exists for the use of RFB with NRTIs. Nine-month SM-based therapy (may be prolonged* to 12 months) ------------------------------------------------------------------------------------------------------------------------------------------------------------------- B.II INH Daily for 2 months INH 2-3 times/week for Can be used concurrently with SM is contraindicated for SM (8 weeks) SM 7 months (30 weeks) antiretroviral regimens that pregnant women. PZA PZA include protease inhibitors, NRTIs, and NNRTIs. Every effort should be made to continue administering SM for the total duration of treatment. When SM is not used for the recommended, 9 months, EMB should be added to the regimen and the treatment duration should be prolonged from 9 months (38 weeks) to 12 months (52 weeks). Six-month RIF-based therapy (may be prolonged* to 9 months) ------------------------------------------------------------------------------------------------------------------------------------------------------------------- A.I INH Daily for 2 months INH Daily or 2-3 times/week Protease inhibitors or NNRTIs SM is contraindicated for RIF (8 weeks) RIF for 4 months (18 weeks) should not be administered pregnant women. PZA& concurrently with RIF. EMB& (or SM) or or NRTIs can be administered concurrently with RIF. INH Daily for 2 weeks and INH 2-3 times/week for If appropriate, patients should be RIF then 2-3 times/week for RIF 4 months (18 weeks) assessed every 3 months t PZA& 6 weeks evaluate the decision to initiate EMB& antiretroviral therapy. (or SM) or or A 2-week "P-450 induction washout" period may be necessary between the last dose of RIF and the first dose of protease inhibitors or NNRTIs. INH 3 times/week for INH 3 times/week for RIF 2 months (8 weeks) RIF 4 months (18 weeks) PZA PZA EMB EMB (or SM) (or SM) ------------------------------------------------------------------------------------------------------------------------------------------------------------------- EMB=ethambutol; INH=isoniazid; PZA=pyrazinamide; RFB=rifabutin; RIF=rifampin; SM=streptomycin. NNRTI=nonnucleoside reverse transcriptase inhibitor; NRTI=nucleoside reverse transcriptase inhibitor. * Duration of therapy should be prolonged for patients with delayed response to therapy. Criteria for delayed response should be assessed at the end of the 2-month induction phase and include a) lack of conversion of the Mycobacterium tuberculosis culture from positive to negative or b) lack or resolution or progression of signs or symptoms of TB. + Continue PZA and EMB for the total duration of the induction phase (8 weeks). & Contimue PZA for the total duration of the induction phase (8 weeks). EMB can be stopped after susceptibility test retults indicate Mycobacterium tuberculosis susceptibility to INH and RIF. =================================================================================================================================================================== Return to top. Table_2A Note: To print large tables and graphs users may have to change their printer settings to landscape and use a small font size. TABLE 2A. Antituberculosis medications: doses, toxicities, and monitoring requirements. ======================================================================================================================================================================================================== Dose in mg/kg (maximum dose) Rout of Administration ------------------------------------------------------------------------------------------ Daily Two times/week * Three times/week* ------------------------- ------------------------ ---------------------------- Drug Children Adults Children Adults Children Adults Adverse Reactions Monitoring Comments -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- INH 10-20 5 20-40 15 20-40 15 Rash Liver function tests Hepatitis risk increases (300 mg) (300 mg) (900 mg) (900 mg) (900 mg) (900 mg) Hepatic enzyme elevation with age and alcohol PO or IM PO or IM PO or IM PO or IM PO or IM PO or IM Hepatitis Repeat measurements if consumption. Peripheral neuropathy baseline results are Mild central nevous abnormal Pyridoxine (Vitamin B6) system effects patient is pregnant or at might prevent peripheral Drug interactions high risk for adverse neuropathy and central resulting in increased reactions nervous system effects. phenytoin (Dilantin) or patient has symptoms of disulfiram (Antabuse) adverse reactions levels RIF 10-20 10 10-20 10 10-20 10 Rash Complete blood count, RIF use contraindicated (600 mg) (600 mg) (600 mg) (600 mg) (600 mg) (600 mg) Hepatitis platelets, and liver for patients taking PIs or PO or IV PO or IV PO or IV PO or IV PO or IV PO or IV Fever function tests NNRTIs. Thrombocytopenia Flu-like symptoms Repeat measurements if Decreases levels of many associated with baseline results are drugs (e.g., methadone, intermittent dosing abnormal dapsone, ketoconazole, Orange-colored body patient has symptoms hormonal contraceptives fluids (secretions, urine, of adverse reactions tears) Might permanently discolor soft contact lenses. RFB+ 10-20 5 10-20 5 Not Not Rash Complete blood count, RFB is contraindicated for (300 mg) (300 mg) (300 mg) (300 mg) known known platelets, and liver platelets, and liver patients taking ritonavir, PO or IV PO or IV PO or IV PO or IV Fever function tests saquinavir (Invirase), or Thrombocytopenia delavirdine. or or or or Orange-colored body Repeat measurements if fluids (secretions, urine, baseline results are Reduces levels of many NA& NA& 10-20& 5& Not Not tears) abnormal drugs (e.g., PIs, NNRTIs, (150 mg) (150 mg) (300 mg) (300 mg) known known patient has symptoms methadone, dapsone, PO or IV PO or IV PO or IV PO or IV With increased levels of of adverse reactions ketoconazole, hormonal RFB: contraceptives). or or or or Not Not Severe arthralgias Use adjusted daily dose known known Uveitis of RFB&, and monitor for Might permanently NA@ NA@ NA@ NA@ Leukopenia decreased antiretroviral discolor soft contact (450 mg) (450 mg) (450 mg) (450 mg) activity and for RFB lenses. PO or IV PO or IV PO or IV PO or IV toxicity if RFB taken concurrently with PIs or NNRTIs. PZA 15-30 15-30 50-70 50-70 50-70 50-70 Gastrointestinal upset Liver function tests and Treat hyperuricemia only (2.0 g) (2.0 g) (3.5 g) (3.5 g) (2.5 g) (2.5 g) Hepatitis uric acid if patient has symptoms. PO PO PO PO PO PO Rash Arthralgias Repeat measurements if Might make glucose Hyperuricemia baseline results are control more difficult in Gout (rare) abnormal persons with diabetes. patient has symptoms of adverse reactions EMB 15-25 15-25 50 50 25-30 25-30 Optic neuritis (decreased Baseline and monthly Optic neuritis might be (1600 mg) (1600 mg) (4000 mg) (4000 mg) (2000 mg) (2000 mg) red-green color tests of visual acuity and unilateral; check each eye PO PO PO PO PO PO discrimination), color vision separately. decreased visual acuity Rash SM 20-40 15 25-30 25-30 25-30 25-30 Otoxicity (hearing loss Baseline and repeat as Ultrasound and warm (1 g) (1 g) (1.5 g) (1.5 g) (1.5 g) (1.5 g) or vestibular dysfunction) needed audiometry and compresses to injection IM or IV IM or IV IM or IV IM or IV IM or IV IM or IV Nephrotoxicity renal function tests site might reduce pain. Maximum dose for patients >=60 years is 1.0 g. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- EMB=ethambutol; INH=isoniazid; PZA=pyrazinamide; RFB=rifabutin; RIF=rifampin; SM=streptomycin. NNRTIs=nonnucleoside reverse transcriptase inhibitors; PI=protease inhibitor. IM=intramuscular; IV=intravenous; PO=by mouth * All intermittent dosing should be administered with directly observed therapy. + The concurrent use of RFB is contraindicated with ritonavir, saquinavir (Invirase), and delavirdine. Information regarding the use of rifabutin with saquinavir (Fortovase), amprenavir, efavirenz, and nevirapine is limited. & Not applicable. If nelfinavir, indinavir, or amprenavir is administered with RFB, blood concentrations of these protease inhibitors decrease. Thus, when RFB is used concurrently with any of these three drugs, the daily dose of RFB is reduced from 300mg to 150mg (the twice-weekly dose of RFB is unchanged, however). @ NA=not applicable. If efavirenz is administered with RFB, blood concentrations of RFB decrease. Thus, when RFB is used concurrently with efavirenz, the dose of RFB for both daily and twice weekly administration should be increased from 300 mg to 450 mg. ======================================================================================================================================================================================================== Return to top. Table_3A Note: To print large tables and graphs users may have to change their printer settings to landscape and use a small font size. TABLE 3A. Tuberculosis (TB) preventive therapy regimens for adults with human immunodeficiency virus (HIV) infection ======================================================================================================================================================== Rating Drug Interval and Duration Comments Indications Conraindications -------------------------------------------------------------------------------------------------------------------------------------------------------- A.II INH Daily for 9 months INH can be administered HIV-infected persons who are History of an INH-induced concurrently with NRTIs, candidates for TB preventive reaction, including hepatic, protease inhibitors, or NNRTIs. therapy. skin, or other allergic reactions or neuropathy. B.I INH 2 times/week for 9 months DOPT must be used when Known exposure to person twice-weekly dosing is used. who has INH-resistant TB. Chronic severe liver disease. A.I RIF and PZA* Daily for 2 months Protease inhibitors or NNRTIs HIV-inifected persons who are History of rifamycin- should not be administered candidates for TB preventive induced reaction, including concurrently with RIF; in this therapy. hepatic, skin, or other allergic situation, an alternative is reactions, or the use of RFB+ and PZA. thrombocytopenia. If RFB is administered, patient HIV-infected persons known Pregnancy. should be monitored carefully to be contacts of patient who for potential RFB drug toxicity has INH-resistant, Chronic severe hyperuricemia. and potential decreased rifamycin-susceptible TB. antiretroviral drug activity. Chronic severe liver disease. Dose adjustments, alternative therapies, or other precautions might be needed with rifamycins are used (e.g., patients using hormonal contraceptives must be advised to use barrier methods, and patients using methodone require dose adjustments). -------------------------------------------------------------------------------------------------------------------------------------------------------- INH=isoniazid; PZA=pyrazinamide; RFB=rifabutin;RIF=rifampin. DOPT=directly observed preventive therapy; NNRTI=nonnucleoside reverse transcriptase inhibitor; NRTO=nucleoside reverse transcriptase inhibitor. * For patients with intolerance to PZA, some experts recommend the use of rifamycin (RIF or RFB) alone for preventive treatment. Most experts agree that available data support the recommendation that this treatment can be administered for as short a duration as 4 months, although some experts would treat for 6 months. + The concurrent use of RFB is contraindicated with ritonavir, hard-gel saquinavir (Invirase), and delavirdine. The information regarding the use of RFB with soft-gel saquinavir (Fortovase), amprenavir, efavirenz, and nevirapine is limited. ======================================================================================================================================================== Return to top. Disclaimer All MMWR HTML versions of articles are electronic conversions from ASCII text into HTML. This conversion may have resulted in character translation or format errors in the HTML version. Users should not rely on this HTML document, but are referred to the electronic PDF version and/or the original MMWR paper copy for the official text, figures, and tables. 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