What is the recommended treatment approach for a patient with HIV (Human Immunodeficiency Virus) and TB (Tuberculosis)?

Treatment of TB in HIV

For HIV-infected patients with tuberculosis, initiate a 6-month rifabutin-based regimen (isoniazid, rifabutin, pyrazinamide, and ethambutol) and start antiretroviral therapy within 2 weeks if CD4 <50 cells/μL or within 8 weeks if CD4 ≥50 cells/μL. 1

TB Treatment Regimen Selection

For Patients on or Starting Protease Inhibitors/NNRTIs

Use rifabutin instead of rifampin due to significant drug interactions that lower serum concentrations of antiretroviral drugs. 2, 1

• Intensive phase (2 months): Isoniazid, rifabutin, pyrazinamide, and ethambutol administered daily for 8 weeks, or daily for at least 2 weeks followed by twice-weekly dosing for 6 weeks 2, 1
• Continuation phase (4 months): Isoniazid and rifabutin administered daily or twice weekly 2, 1

Rifabutin dose adjustments are critical:

• Reduce from 300 mg to 150 mg daily when used with indinavir, nelfinavir, or amprenavir 1
• Increase from 300 mg to 450 mg daily when used with efavirenz 1

For Patients NOT on Antiretroviral Therapy

If both patient and clinician agree to delay ART initiation, use the standard rifampin-based regimen:

• Intensive phase (2 months): Isoniazid, rifampin, pyrazinamide, and ethambutol (or streptomycin) administered daily for 8 weeks, or daily for at least 2 weeks followed by 2-3 times weekly for 6 weeks 2
• Continuation phase (4 months): Isoniazid and rifampin administered daily or 2-3 times weekly 2

For Patients with Rifamycin Intolerance or Contraindication

Use a 9-month non-rifamycin regimen:

• Intensive phase (2 months): Isoniazid, streptomycin, pyrazinamide, and ethambutol 2
• Continuation phase (7 months): Isoniazid, streptomycin, and pyrazinamide administered 2-3 times weekly 2

Timing of Antiretroviral Therapy Initiation

The timing of ART is stratified by CD4 count and has direct mortality implications:

CD4 <50 cells/μL

• Start ART within 2 weeks of TB treatment initiation 1, 3, 4
• This approach reduces mortality by 6% (absolute risk reduction) 5

CD4 ≥50 cells/μL

• Start ART within 8-12 weeks of TB treatment initiation 1, 3, 4
• Earlier initiation in this group does not improve survival but increases IRIS risk 5, 6

Exception: TB Meningitis

• Delay ART for 8 weeks due to increased risk of life-threatening immune reconstitution inflammatory syndrome 1

Critical Drug Interaction Management

Rifampin is a potent CYP450 inducer that dramatically lowers protease inhibitor and NNRTI levels, rendering HIV treatment ineffective. 2

Key timing consideration: Rifampin's CYP450 induction continues for at least 2 weeks after discontinuation. Plan a 2-week washout period between the last rifampin dose and first dose of protease inhibitors or NNRTIs. 2

Staggered Therapy Approach for Treatment-Naive Patients

Consider delaying ART initiation to promote adherence and reduce overlapping toxicities:

• Start ART at the end of the 2-month intensive TB phase, OR 2
• Start ART after TB therapy completion 2

During the delay period, monitor every 3 months:

• HIV viral load 2
• CD4+ T-cell counts 2
• Clinical HIV status 2

Essential Supportive Measures

Directly Observed Therapy (DOT)

Implement DOT for all HIV-TB coinfected patients to ensure adherence and prevent drug resistance. 2, 1, 7

Pyridoxine Supplementation

Administer pyridoxine (vitamin B6) 25-50 mg daily to all HIV-infected patients receiving isoniazid to prevent peripheral neuropathy. 2, 1, 8

Monitoring Requirements

Baseline Assessment

• Drug susceptibility testing on TB isolates 8, 7
• Liver function tests 8
• Serum creatinine 9
• Platelet count 9
• CD4 count and HIV viral load 9

Follow-up Monitoring

• Sputum microscopy and culture at 2 months to assess TB treatment response 2, 1
• Sputum microscopy at 5 months and end of treatment 2
• CD4 count and HIV viral load every 3 months 1, 8
• Regular liver function monitoring due to overlapping hepatotoxicity from multiple medications 8, 3

Management of Immune Reconstitution Inflammatory Syndrome (IRIS)

IRIS occurs more frequently with earlier ART initiation (incidence 8.86 vs 5.02 per 100 person-months). 6

Treatment approach:

• Mild IRIS: Nonsteroidal anti-inflammatory drugs 1
• Severe IRIS: Prednisone 1-2 mg/kg/day for 1-2 weeks, then taper 1
• Continue both TB and HIV treatment unless life-threatening complications occur 2, 8

Treatment Duration Considerations

Standard duration is 6 months (180 daily doses) for drug-susceptible TB. 1, 3

Extend to 9 months if:

• CD4 <100 cells/μL 1
• Cavitation on chest X-ray 1
• Positive cultures at 2 months 1
• Delayed clinical response 1

Critical Pitfalls to Avoid

Never use rifampin in patients on protease inhibitors or NNRTIs - this causes treatment failure of either HIV or TB due to severe drug interactions. 9

Never interrupt established ART to accommodate rifampin use - this increases mortality risk. 9

Never use three-drug regimens without a rifamycin, aminoglycoside, or capreomycin for HIV-related TB; if unavoidable, treat for minimum 18 months. 2

Never delay TB treatment to optimize HIV regimen - start TB treatment immediately and adjust HIV regimen as needed. 2