Tb preventive therapy

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TB Preventive Therapy (TPT)

TB preventive therapy (also called treatment of latent TB infection, LTBI) reduces the viable bacilli population in inactive lesions, preventing progression to active TB. It can also prevent establishment of infection after exposure ("primary prophylaxis").

Who Should Receive TPT

Indications are listed in order of decreasing risk:

1. People Living with HIV (PLHIV)

TB rates in HIV/M. tuberculosis co-infection: 3–16% per year; PLHIV are 21× more likely to develop active TB than HIV-negative individuals
WHO recommends TPT for all PLHIV without evidence of active TB, regardless of TST or IGRA result
Preventive therapy reduces TB incidence (RR 0.68 vs. placebo); benefit is greater in TST-positive individuals (RR 0.38)
Consider 36-month duration in high-burden settings (conditionally recommended by WHO) to reduce reinfection risk

2. Close Contacts of Infectious TB Cases

2–4% develop TB within 1 year of close contact; risk is higher in children and adolescents
All close contacts should be treated (TST/IGRA may be negative early)
TST ≥5 mm → full course of TPT
TST negative → retest 2–3 months later; if still negative, discontinue; if converted, continue full course
HIV-positive contacts: treat even if TST is negative

3. Persons With Recent Infection

Risk is greatest in the first 1–2 years after infection
TST conversion = increase of ≥10 mm within 2 years (for most persons)
All documented converters should receive treatment

4. Persons With Other High-Risk Conditions Sufficient evidence to warrant TPT in:

Fibrotic lesions on chest X-ray (old, untreated TB)
Organ transplant recipients (immunosuppression)
TNF-α inhibitor therapy
Silicosis
Chronic renal failure / dialysis
Diabetes mellitus
Prolonged corticosteroid use
Malignancies (especially hematologic)

Treatment Regimens

These apply when infection is presumed susceptible to isoniazid or rifampin (guidelines updated February 2020):

Preferred Regimens

Regimen	Duration	Frequency	Key Notes
Isoniazid + Rifapentine (3HP)	3 months	Once weekly × 12 doses	Non-inferior to 9H; higher completion rates; suitable for adults & children >2 yrs (with or without HIV)
Rifampin alone (4R)	4 months	Daily	Preferred for HIV-negative; dose: 10 mg/kg adults, 15–20 mg/kg children (max 600 mg); watch drug interactions
Isoniazid + Rifampin (3HR)	3 months	Daily	Conditionally recommended; for adults & children ± HIV

Doses for 3HP (age ≥12 yrs):

Isoniazid: 15 mg/kg (rounded to nearest 50/100 mg, max 900 mg)
Rifapentine: 300 mg (10–14 kg) → 900 mg (>50 kg)

Alternative Regimens

Regimen	Duration	Recommendation
Isoniazid (6H)	6 months daily	Strongly recommended for HIV-negative; conditional for HIV-positive
Isoniazid (9H)	9 months daily	Conditionally recommended (all ages, ± HIV)

Adult isoniazid dose: 5 mg/kg/day (max 300 mg/day) OR 15 mg/kg twice weekly (max 900 mg) for DOT
Isoniazid reduced TB incidence by approximately 60% in clinical trials; protective effect persists 10–12 years

Special Situations & Monitoring

Contraindications / Cautions:

Active unstable liver disease → do not give isoniazid or rifamycin
Stable chronic liver disease → can proceed with close monitoring
Pregnancy → generally defer until after delivery; exceptions: documented TST conversion during pregnancy, HIV-infected with positive TST (start immediately)

Monitor closely in:

Age >35 years
Alcohol use disorder, diabetes mellitus, renal insufficiency
Concurrent medications (phenytoin, disulfiram, antiretroviral drugs)
Main adverse effects: hepatitis and peripheral neuropathy

Drug Interactions:

Rifamycins (rifampin, rifapentine) induce CYP3A and P-glycoprotein — significant interactions with antiretrovirals, anticoagulants, and other drugs
Rifabutin can substitute for rifampin in HIV/TB co-treatment when interaction management is complex

HIV Co-infection — Additional Considerations

TPT benefit persists in persons receiving ART
36-month isoniazid may further reduce TB risk in high-incidence settings by reducing reinfection
For active TB in PLHIV already on ART: standard 6-month regimen; if not on ART, extend continuation phase to 7 months (total 9 months)
Rifabutin substitution for rifampin is a practical option with dolutegravir-based ART

— Murray & Nadel's Textbook of Respiratory Medicine, pp. 1167–1168 — Goldman-Cecil Medicine, p. 3260

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