Latent Tuberculosis Infection in Patients With HIV

Background

• Latent tuberculosis infection (LTBI) is defined as the presence of a Mycobacterium tuberculosis-specific immune response in the absence of clinical and radiological disease.
• In 2018, it was estimated that 10 million people developed tuberculosis (TB) (incidence of 130 cases per 100,000 persons).
• In 2018, an estimated 862,000 (8.6%) new cases of TB occurred in patients with HIV and 251,000 HIV deaths were attributed to TB.
• Regions endemic for HIV are also endemic for TB.
• HIV is the single most important risk factor for TB.
• Additional risk factors include residence in TB-endemic regions, close contact with patients with TB, crowded housing (including incarceration), poor ventilation in living or working quarters, poor nutrition, and limited access to quality health care.

Evaluation

• Perform testing for latent tuberculosis infection (LTBI) in all persons with HIV.
• Options for testing include the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs).
• TST assesses for a delayed hypersensitivity response to an intradermally injected Mycobacterium tuberculosis purified protein derivative and requires a reading 48-72 hours after the injection.
  • For those with HIV infection, a positive TST is defined as induration ≥ 5 mm.
  • Advanced HIV infection is associated with reduced TST reactivity and decreased sensitivity of the test.
• IGRAs measure levels of interferon induced by M. tuberculosis antigens in the blood.
• Select IGRAs for testing when patients are unlikely to return to obtain a TST or in persons with a history of Bacille Calmette-Guérin (BCG) vaccination.
• A negative TST or IGRA does not definitively exclude a diagnosis of tuberculosis (TB).
• In all patients with HIV infection and suspected LTBI or symptoms of TB, perform chest radiography and clinical evaluation promptly to rule out active TB.

Management

• Treat patients with HIV for latent tuberculosis infection (LTBI) when:
  • the patient has a positive diagnostic test for LTBI, no evidence of tuberculosis (TB) disease, and no prior history of treatment for active or latent TB (Strong recommendation)
  • the patient is a close contact of persons with infectious pulmonary TB, regardless of LTBI status (Strong recommendation)
• Rule out active TB prior to initiating treatment for LTBI, as treatment of active disease with regimens to treat LTBI can lead to development of drug-resistant TB.
• Recommended treatment regimens:
  • The preferred regimen is isoniazid (INH) 300 mg orally once daily plus pyridoxine 25-50 mg orally once daily (Strong recommendation).
  • Alternative regimens include:
    • rifapentine (weight-based, 900 mg maximum) plus isoniazid 15 mg/kg weekly (900 mg maximum) plus pyridoxine 50 mg weekly orally for 12 weeks for patients having ART regimens containing efavirenz or raltegravir (Strong recommendation)
    • rifampin 600 mg/day orally for 4 months (Weak recommendation)
  • CDC issues guidance regarding use of rifampin and rifapentine for treatment of active and latent TB infection after some manufacturers detect nitrosamine impurities in their products.
  • 2-month regimen of pyrazinamide plus rifampin is not recommended for prophylaxis due to increased risk for fatal and severe hepatotoxicity (Strong recommendation).
  • For patients exposed to drug-resistant Mycobacterium tuberculosis, select anti-TB drugs after consultation with experts or public health authorities (Strong recommendation).
  • Give ART in addition to LTBI treatment to reduce the risk of TB disease (Strong recommendation).
  • Dose adjustments of antiretroviral drugs and/or TB drugs may be required due to drug-drug interactions.
• Treatment for LTBI reduces the risk of developing active TB by about 60%.
• Consider longer courses of preventive therapy in settings where rates of TB are high and there is a risk of ongoing transmission and reinfection with M. tuberculosis.