What is the recommended treatment regimen for a patient with both tuberculosis (TB) and Human Immunodeficiency Virus (HIV) infection?

TB Treatment in HIV-Infected Patients

For HIV-infected patients with drug-susceptible tuberculosis, initiate a 6-month daily regimen of isoniazid, rifabutin (or rifampin if not on certain antiretrovirals), pyrazinamide, and ethambutol, and start antiretroviral therapy (ART) within 2 weeks if CD4 <50 cells/μL or within 8-12 weeks if CD4 ≥50 cells/μL. 1

Core TB Treatment Regimen

Initial Intensive Phase (2 months)

• Administer isoniazid, rifabutin, pyrazinamide, and ethambutol daily for 8 weeks 1, 2
• Rifabutin is preferred over rifampin when patients are taking protease inhibitors or NNRTIs due to fewer drug interactions 1, 2
• For patients not on antiretrovirals or on compatible ART regimens (not containing protease inhibitors/NNRTIs), rifampin-based regimens remain acceptable 1

Continuation Phase (4 months)

• Continue isoniazid and rifabutin (or rifampin) daily or twice weekly for 4 months 1, 2
• Daily therapy is mandatory for HIV-infected patients—intermittent dosing increases risk of relapse and acquired rifamycin resistance, particularly in those with CD4 counts <100 cells/μL 1

Critical Timing of Antiretroviral Therapy

The timing of ART initiation directly impacts mortality:

• CD4 <50 cells/μL: Start ART within 2 weeks of TB treatment initiation 1, 2, 3
• CD4 ≥50 cells/μL: Start ART within 8-12 weeks of TB treatment initiation 1, 2
• Exception: TB meningitis—delay ART for 8 weeks due to increased risk of life-threatening immune reconstitution inflammatory syndrome (IRIS) 1, 3
• For patients already on established ART with undetectable viral load, continue ART without interruption 3

Drug Interactions and Dosing Adjustments

Rifabutin Dosing with Antiretrovirals

• When used with indinavir, nelfinavir, or amprenavir: reduce rifabutin from 300 mg to 150 mg daily 1
• When used with efavirenz: increase rifabutin from 300 mg to 450 mg daily 1
• Twice-weekly rifabutin dosing remains 300 mg regardless of concurrent antiretroviral use 1

Critical Pitfall to Avoid

Never use rifampin in patients taking protease inhibitors or NNRTIs—this causes treatment failure of either HIV or TB due to severe drug interactions 1, 3

Essential Supportive Measures

• Administer pyridoxine (vitamin B6) 25-50 mg daily to all HIV-infected patients receiving isoniazid to prevent peripheral neuropathy 1, 2, 3
• Implement directly observed therapy (DOT) for all HIV-TB coinfected patients to ensure adherence and prevent drug resistance 1, 2, 3
• Provide co-trimoxazole prophylaxis for patients with CD4 <200 cells/μL to reduce morbidity and mortality 1

Monitoring Requirements

Baseline Assessment

• Drug susceptibility testing on all TB isolates 2, 3
• Liver function tests, serum creatinine, platelet count 3
• CD4 count and HIV viral load 3
• Hepatitis B and C serology if not previously done 1

Ongoing Monitoring

• Sputum microscopy and culture at 2 months to assess treatment response 2, 3
• CD4 count and HIV viral load every 3 months 1, 2, 3
• Liver function tests regularly due to overlapping hepatotoxicity from multiple medications 1, 2
• Monitor for IRIS, particularly in first 2-8 weeks after ART initiation 1, 3

Management of Immune Reconstitution Inflammatory Syndrome (IRIS)

• IRIS presents as paradoxical worsening of TB symptoms (fever, lymphadenopathy, worsening radiographic findings) after ART initiation 1
• Rule out treatment failure and other infections before diagnosing IRIS 1, 3
• Treat mild IRIS with nonsteroidal anti-inflammatory drugs 1
• For severe IRIS: consider prednisone 1-2 mg/kg/day for 1-2 weeks, then taper 1
• Generally do not stop TB treatment or ART unless life-threatening complications occur 4

Special Populations

Pregnant Women

• Treat immediately with rifamycin-containing regimens including pyrazinamide—benefits outweigh potential risks 1
• Avoid aminoglycosides (streptomycin, kanamycin, amikacin) due to fetal toxicity 1

Children

• Use same regimens as adults with appropriate weight-based dosing 1
• Include ethambutol 15 mg/kg even in young children when drug resistance is suspected 1

Drug-Resistant TB in HIV

Isoniazid-Resistant TB

• Use rifabutin, pyrazinamide, and ethambutol for 6-9 months or 4 months after culture conversion 1

Rifampin-Resistant TB

• Use 9-month regimen: isoniazid, streptomycin, pyrazinamide, and ethambutol for 2 months, then isoniazid, streptomycin, and pyrazinamide for 7 months 1

Multidrug-Resistant TB (MDR-TB)

• Consult MDR-TB expert immediately 1
• Consider BPaL/BPaLM regimen (bedaquiline, pretomanid, linezolid ± moxifloxacin) for 6 months—highly effective in HIV-coinfected patients 5, 6, 7
• Treatment duration: 24 months after culture conversion for traditional MDR regimens 1

Treatment Duration Considerations

• Standard duration: 6 months (180 daily doses) 1, 3
• Extend to 9 months if: CD4 <100 cells/μL, cavitation on chest X-ray, positive cultures at 2 months, or delayed clinical response 3
• Once-weekly rifapentine continuation regimens are contraindicated in HIV-infected patients due to unacceptably high relapse rates 1