According to the Indian National Tuberculosis Elimination Programme, what are the recommended tuberculosis preventive treatment regimens, including first‑line 3‑month weekly isoniazid‑rifapentine dosing by weight, alternative regimens, and special recommendations for people living with human immunodeficiency virus, pregnant or lactating women, and patients with liver disease?

India TB Preventative Therapy Guidelines

First-Line Recommended Regimen: 3-Month Weekly Isoniazid-Rifapentine (3HP)

The Indian National Tuberculosis Elimination Programme should adopt 3-month once-weekly isoniazid plus rifapentine (3HP) as the preferred first-line regimen for tuberculosis preventive treatment, based on its superior completion rates, lower hepatotoxicity, and equivalent efficacy to 9-month isoniazid. 1, 2

Weight-Based Dosing for 3HP Regimen

• Adults and adolescents ≥12 years: Rifapentine 900 mg plus isoniazid 900 mg once weekly for 12 weeks under direct observation 1, 3
• Children <12 years: Rifapentine is not currently recommended due to insufficient safety data 3
• This regimen must be administered under directly observed therapy (DOT) to ensure adherence 1, 4

Alternative Regimens

For Patients Unable to Take 3HP

• 4 months of daily rifampin (10 mg/kg, maximum 600 mg): Strongly recommended for HIV-negative adults with moderate-quality evidence; offers shorter duration than isoniazid regimens 1, 2
• 3 months of daily isoniazid (5 mg/kg, maximum 300 mg) plus rifampin (10 mg/kg, maximum 600 mg): Conditionally recommended, particularly when adherence to longer regimens is uncertain 1, 2
• 9 months of daily isoniazid (5 mg/kg, maximum 300 mg): Historically standard therapy with >90% efficacy if completed, but lower completion rates 1, 2
• 6 months of daily isoniazid: Conditionally recommended; less effective than 9-month regimen but may be better tolerated 1, 2

Special Population Recommendations

People Living with HIV (PLHIV)

• When isoniazid is chosen, use 9 months (not 6 months) duration 5, 1
• Rifapentine is contraindicated in HIV-infected patients due to increased risk of rifampin resistance with currently recommended dosages 3
• Rifabutin may substitute for rifampin when drug-drug interactions with protease inhibitors or NNRTIs are problematic 5, 1
• Rifampin is contraindicated with protease inhibitors or non-nucleoside reverse transcriptase inhibitors; rifabutin is also contraindicated with ritonavir, hard-gel saquinavir, and delavirdine 5
• For HIV-infected patients not on protease inhibitors/NNRTIs: 2-month daily rifabutin plus pyrazinamide is an option 5

Pregnant or Lactating Women

• For HIV-negative pregnant women: Daily or twice-weekly isoniazid for 9 or 6 months is recommended 5, 1
• For high-risk pregnant women (HIV-infected or recently infected): Initiation should not be delayed even during the first trimester 5, 1
• For lower-risk pregnant women: Some experts recommend deferring therapy until after delivery 1
• Pyridoxine supplementation should accompany isoniazid to prevent peripheral neuropathy 1
• Rifapentine is not recommended in pregnant or lactating women due to insufficient safety data 3
• Women can breastfeed normally while taking antituberculosis drugs 5

Patients with Liver Disease

• Baseline liver function tests (AST/ALT, bilirubin) are mandatory for patients with chronic liver disease, regular alcohol use, hepatitis B or C positivity, or clinical suspicion of liver disorder 5, 1
• Baseline testing is NOT routinely required for all patients or based solely on age 1, 2
• Weekly liver function tests for the first 2 weeks, then every 2 weeks during the first 2 months of treatment in patients with known chronic liver disease 5
• Withhold isoniazid if transaminases exceed 3× upper limit of normal (ULN) with symptoms or 5× ULN without symptoms 1, 2
• Active hepatitis and end-stage liver disease are relative contraindications to isoniazid or pyrazinamide 1, 2
• Rifampin, isoniazid, and pyrazinamide can be given in standard dosage despite potential hepatotoxicity; the addition of pyrazinamide does not increase morbidity 5

Children and Adolescents

• Isoniazid daily (10-15 mg/kg, maximum 300 mg) or twice-weekly for 9 months is recommended 1
• 12-month isoniazid regimen is recommended by the American Academy of Pediatrics for HIV-infected children 5
• Under India's National TB Elimination Program, all household contacts aged <6 years receive daily isoniazid (5 mg/kg) for 6 months 6, 7

Contacts of Drug-Resistant TB

• For isoniazid-resistant, rifamycin-susceptible TB contacts: 2-month daily rifampin plus pyrazinamide, or 4-month rifampin alone if pyrazinamide intolerance 5, 1
• For multidrug-resistant TB contacts: Pyrazinamide plus ethambutol OR pyrazinamide plus fluoroquinolone (levofloxacin/ofloxacin) for 6-12 months; minimum 6 months for immunocompetent, 12 months for immunocompromised 1
• Drug selection must be guided by susceptibility testing of the source case 1

Mandatory Pre-Treatment Requirements

• Active tuberculosis must be definitively excluded through detailed history, physical examination, chest radiography, and when indicated, bacteriologic studies 1, 2
• Screen for TB symptoms: Cough >2-3 weeks, hemoptysis, fever, night sweats, weight loss, chest pain, dyspnea, and fatigue 1
• Obtain three consecutive sputum specimens for AFB smear and culture if chest X-ray is abnormal or respiratory symptoms are present 1
• In HIV-infected patients with respiratory symptoms, collect sputum even if chest X-ray appears normal 1

Clinical Monitoring During Treatment

For Isoniazid-Only or Rifampin-Only Regimens

• Monthly clinical evaluations to assess for fever, malaise, vomiting, jaundice, or unexplained deterioration 5, 1
• Patients must stop medication immediately and seek urgent care if they develop symptoms of hepatotoxicity 1, 2

For Rifampin Plus Pyrazinamide Regimens

• Clinical assessments at weeks 2,4, and 8 1
• This regimen is associated with significantly more treatment-limiting adverse events and hepatotoxicity compared to isoniazid alone 8

Laboratory Monitoring

• Reserved for patients with abnormal baseline tests or high-risk groups (HIV-infected, pregnant/postpartum ≤3 months, chronic liver disease, regular alcohol use) 1, 2
• Not routinely indicated for all patients 1, 2

Critical Pitfalls to Avoid

• Never initiate preventive therapy without definitively excluding active TB disease; treating unrecognized active TB with monotherapy promotes drug resistance 1, 2
• Never use rifapentine in HIV-infected patients due to increased risk of rifampin resistance 3
• Never assume normal chest X-ray excludes TB in immunocompromised patients; maintain high clinical suspicion and collect sputum if symptoms present 1
• Never perform routine baseline liver testing in all patients; limit to high-risk groups to avoid over-testing 1, 2
• Always verify antiretroviral compatibility before prescribing rifamycin-based regimens in HIV patients to avoid treatment failure 1
• Never ignore symptoms of hepatotoxicity; patients must stop treatment immediately if fever, malaise, vomiting, or jaundice develop 1, 2

Operational Challenges in India

• Contact screening and IPT implementation under routine programmatic conditions is sub-optimal in India, with only 67% of eligible children evaluated and 84% of those initiated on IPT 7
• Rural household contacts are significantly less likely to be evaluated and initiated on IPT (risk ratio 6.65) 7
• Non-adherence rates are high: 54.7% of children missed at least two doses in the previous 7 days, attributed to forgetfulness (37%), carelessness (39%), and intermittent stopping (27%) 6
• Shortage of isoniazid tablets in peripheral health centers prevents initiation in eligible contacts 7
• Urgent need to sensitize program staff and establish rigorous monitoring mechanisms 7