What is the recommended treatment regimen for a patient with tuberculosis (TB) and human immunodeficiency virus (HIV) infection?

Management of Tuberculosis in HIV-Positive Patients

Initial Treatment Regimen

All HIV-infected patients with tuberculosis should receive a 6-month rifamycin-based regimen consisting of isoniazid, rifabutin (preferred) or rifampin, pyrazinamide, and ethambutol for the initial 2-month intensive phase, followed by isoniazid and rifabutin/rifampin for the 4-month continuation phase. 1, 2, 3

Intensive Phase (First 2 Months)

• Administer daily isoniazid, rifabutin, pyrazinamide, and ethambutol 1, 2, 3
• Daily therapy is mandatory for all HIV-coinfected patients; intermittent dosing during the intensive phase should be avoided due to increased risk of relapse with acquired rifamycin resistance 4
• The minimum is 14 daily doses (one dose per day for 2 weeks) followed by 12 induction doses (two doses per week for 6 weeks) if intermittent therapy is used 1

Continuation Phase (Months 3-6)

• Continue isoniazid and rifabutin/rifampin daily or twice weekly for 4 months 1, 2
• Complete at least 180 doses (one dose per day for 6 months) or 36 continuation doses (two doses per week for 18 weeks) 1

Rifamycin Selection: Critical Drug Interaction Considerations

Rifabutin is strongly preferred over rifampin in HIV-infected patients receiving antiretroviral therapy, particularly those on protease inhibitors or NNRTIs, due to significantly fewer drug interactions. 1, 2

Rifabutin Dosing Adjustments with Antiretrovirals

• With indinavir, nelfinavir, or amprenavir: Reduce rifabutin from 300 mg to 150 mg daily 1
• With efavirenz: Increase rifabutin from 300 mg to 450 mg daily 1
• Twice-weekly dosing: Use 300 mg regardless of concurrent protease inhibitor use 1
• With soft-gel saquinavir or nevirapine: Dose adjustments are uncertain; expert consultation recommended 1

When Rifampin Can Be Used

• Rifampin may be used if the patient is not yet on antiretroviral therapy and ART initiation can be appropriately timed 1
• Critical pitfall: Never use rifampin in patients on protease inhibitors or NNRTIs, as this causes treatment failure of either HIV or TB due to severe drug interactions 2

Antiretroviral Therapy Management

Continue antiretroviral therapy without interruption in patients already on ART with undetectable viral load, as stopping ART risks virological rebound and immune deterioration. 2

Timing of ART Initiation in Treatment-Naive Patients

• CD4 count <50 cells/mm³: Initiate ART within 2 weeks of starting TB treatment 5, 6, 7
• CD4 count ≥50 cells/mm³: Initiate ART within 8 weeks of starting TB treatment 5, 6, 7
• ART should be initiated in all HIV-infected patients with TB, irrespective of CD4 cell count 6

Preferred ART Regimens

• NNRTI-based regimens remain first-line in resource-limited settings 6
• Efavirenz is preferred over nevirapine due to more favorable treatment outcomes 6
• If using raltegravir with rifampin, double the dose to 800 mg twice daily 2

Treatment Duration and Extension Criteria

The minimum duration is 6 months (180 daily doses), but extend to 9 months in patients with delayed response or specific risk factors. 1, 2

Extend Treatment to 9 Months If:

• CD4 count <100 cells/mm³ 2
• Cavitation on chest X-ray 2
• Positive sputum cultures at 2 months 2
• Delayed clinical or microbiological response 1, 2

Calculating Treatment Completion

• Completion is based on total number of doses administered, not duration alone 1
• Interruptions due to drug toxicity must be accounted for when calculating the end-of-therapy date 1

Essential Supportive Measures

Pyridoxine Supplementation

• Administer pyridoxine (vitamin B6) 25-50 mg daily to all HIV-infected patients receiving isoniazid to prevent peripheral neuropathy 2, 5

Directly Observed Therapy (DOT)

• Implement DOT for all HIV-TB coinfected patients to ensure adherence and prevent drug-resistant TB 1, 2, 8, 3
• DOT is mandatory for twice-weekly or thrice-weekly regimens 3

Drug-Resistant Tuberculosis

Isoniazid-Resistant TB

• Use rifabutin, pyrazinamide, and ethambutol for 6-9 months or 4 months after culture conversion 1
• Stop isoniazid when high-level resistance (>1% bacilli resistant to 1.0 µg/mL) is confirmed 1
• Consider continuing isoniazid if only low-level resistance is present 1

Rifampin-Resistant TB

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

Multidrug-Resistant TB (MDR-TB)

• Consult experts experienced in MDR-TB management immediately 1, 5
• Use regimens including aminoglycosides and fluoroquinolones 1
• Treat for 24 months after culture conversion 1
• For newer MDR-TB regimens, a 6-month combination of bedaquiline, pretomanid, linezolid, and moxifloxacin is now standard 9

Special Populations

Pregnant Women with HIV and TB

• Treat without delay using rifamycin-containing regimens 1
• Pyrazinamide is recommended despite inadequate teratogenicity data, as benefits outweigh risks 1
• Contraindicated: Aminoglycosides (streptomycin, kanamycin, amikacin) and capreomycin due to fetal toxicity 1

Children with HIV and TB

• Include ethambutol at 15 mg/kg even in young children who cannot be monitored for visual acuity, unless the strain is known to be susceptible to isoniazid and rifampin 1
• A 4-month regimen of standard TB drugs is non-inferior to 6 months for non-severe, drug-sensitive TB 9

Extrapulmonary and CNS Tuberculosis

• Use the same 6-month rifabutin-based regimen as pulmonary TB 2
• Consider extending to 9 months for CNS involvement, especially if CD4 <100 cells/mm³ 2
• Monitor closely for paradoxical reactions and immune reconstitution inflammatory syndrome (IRIS) 2

Monitoring Requirements

Baseline Assessments

• Drug susceptibility testing on all TB isolates 2, 5, 3
• Liver function tests, serum creatinine, platelet count 2
• CD4 count and HIV viral load 2

Follow-Up Monitoring

• Sputum microscopy and culture at 2 months 2, 5
• CD4 count and HIV viral load every 3 months 2, 5
• Regular liver function monitoring due to hepatotoxicity risk from multiple medications 5
• HIV-infected patients with hepatitis C coinfection have 14-fold increased risk of drug-induced hepatotoxicity 5

Critical Pitfalls to Avoid

• Never interrupt ART to accommodate rifampin use, as this increases mortality risk 2
• Never use rifampin with protease inhibitors or NNRTIs without switching to rifabutin 2
• Never use intermittent dosing during the intensive phase in HIV-coinfected patients 4
• Never delay TB treatment while waiting to optimize HIV therapy; TB treatment takes priority 1, 2
• Never use rifapentine in HIV-infected patients, as safety and effectiveness are not established 1
• Never assume treatment completion based on time alone; count actual doses administered 1