Tuberculosis Preventive Therapy (TPT) Regimens
Recommended First-Line Regimens
For most adults and children with latent TB infection, use either 3 months of once-weekly isoniazid plus rifapentine (3HP) or 4 months of daily rifampin as the preferred regimens due to superior completion rates and safety profiles. 1
Standard Regimen Options
3HP (3 months once-weekly isoniazid + rifapentine): This regimen has equivalent effectiveness to 9 months of isoniazid with higher completion rates and less hepatotoxicity in HIV-negative persons 1, 2
4 months daily rifampin (4R): Demonstrates significantly better completion than 9-month isoniazid with significantly less toxicity, especially hepatotoxicity 3, 4
9 months daily isoniazid (9H): Provides over 90% efficacy when completed properly, though completion rates are lower than shorter regimens 5, 3
6 months daily isoniazid (6H): Widely used alternative, though less effective than 9-month regimens 6
HIV-Infected Individuals
HIV-infected adults should receive 9-12 months of daily isoniazid as the standard regimen. 7, 5
Regimen Selection Based on Antiretroviral Therapy
For patients on protease inhibitors or NNRTIs: Use 9-month isoniazid daily or twice weekly (with directly observed therapy for intermittent dosing) 7
For patients NOT on protease inhibitors or NNRTIs: May use 2 months of daily rifampin and pyrazinamide as an alternative 7, 5
Rifabutin substitution: Can replace rifampin when drug interactions with antiretrovirals are a concern, but avoid concurrent use with ritonavir, hard-gel saquinavir, or delavirdine 7
HIV-infected children: The American Academy of Pediatrics recommends 12 months of daily isoniazid 7, 1
Special Populations
Pregnant Women
For pregnant HIV-infected women who are candidates for TPT, initiate 9-month isoniazid regimen immediately without delay, even during the first trimester. 7, 5
Contacts of Drug-Resistant TB
Isoniazid-resistant, rifamycin-susceptible TB contacts: Use 2 months of rifamycin (rifampin or rifabutin) plus pyrazinamide 7, 5
Pyrazinamide intolerance: Use 4-6 months of rifamycin alone 7
Multidrug-resistant TB contacts: Use combination of at least two drugs the strain is susceptible to (e.g., ethambutol and pyrazinamide, or levofloxacin and ethambutol), based on source patient's drug susceptibility pattern 7
Dosing Schedules and Administration
Daily vs. Intermittent Therapy
Daily administration: Preferred approach for all regimens 8, 5
Twice-weekly administration: Acceptable for isoniazid regimens but requires directly observed therapy (DOT) 7, 5
DOT requirement: Always use DOT with intermittent dosing regimens; also recommended for 2-month preventive therapy regimens and in institutional settings 7
Treatment Completion Criteria
Completion is based on total doses administered, not calendar duration alone. 1, 5
Daily isoniazid: Minimum 270 doses over 9 months (up to 12 months if interruptions occur) 7, 1, 5
Daily rifamycin plus pyrazinamide: Minimum 60 doses over 2 months 7, 5
Monitoring Requirements
Monthly Clinical Evaluation
All persons on TPT must receive monthly clinical evaluation to assess adherence and medication side effects. 7, 1, 5
Laboratory Monitoring
Baseline assessment: For persons over age 35, obtain transaminase measurement before initiation 1, 5
Ongoing monitoring: Monthly transaminase measurements until completion for those over 35 years 1, 5
Symptom-based monitoring: All patients should be questioned about reactions at each monthly visit, even if no problems are apparent 7
Pyridoxine Supplementation
- HIV-infected patients: Administer pyridoxine 25-50 mg daily or 50-100 mg twice weekly with isoniazid to reduce central and peripheral nervous system side effects 5
Critical Pitfalls and Caveats
Pre-Treatment TB Exclusion
Active TB disease must be ruled out before initiating TPT. 6 The balance between thorough screening and maintaining TPT access is crucial:
Symptom-only screening: Allows broader access but may include individuals with subclinical TB 4
Radiographic screening: Detects subclinical TB but if it reduces TPT access by more than 10-30%, it may reduce overall TB prevention impact 4
Drug Resistance Considerations
Community-wide IPT programs: May generate selective pressure favoring drug-resistant strains through suppression of drug-sensitive infections, even without directly selecting for resistance in treated individuals 9
Rifamycin-based regimens: When prescribed after symptom-only screening, 4 months rifampin averts 12-37 active TB cases for each net rifampicin resistance case added 4
Treatment Interruptions
Interruptions >2 months: Require medical examination to rule out TB disease before restarting therapy 7
Reinitiation options: Either continue the original regimen to complete recommended duration, or restart the entire regimen 7
Drug Interactions
Methadone: Patients on rifampin require increased methadone dosage to avoid withdrawal symptoms 7, 8
Antiretroviral therapy: Rifampin cannot be used with protease inhibitors or NNRTIs due to drug interactions 7
Post-Treatment Follow-Up
Follow-up care including chest x-rays and medical evaluations is not necessary for patients who complete TPT, unless they develop symptoms of active TB or are subsequently reexposed to infectious TB. 7
For those who do not receive TPT despite being candidates, assess periodically (at intervals <6 months) for TB symptoms as part of ongoing care, and educate about symptoms requiring immediate medical attention (cough with or without fever, night sweats, weight loss). 7