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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.
========================================================================================================================================================
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