Active Tuberculosis in Patients With HIV Infection

Background

• In 2018, an estimated 862,000 (8.6%) new cases of tuberculosis (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 infection is the most important risk factor for TB, and persons with HIV are 20-30 times more likely to develop TB than persons who are HIV-negative.
• 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.
• Clinical manifestations of TB in patients with HIV vary and depend on patient age, immune status, and sites of TB.
  • Pulmonary TB is the most common presentation.
  • Extrapulmonary TB is more common in patients with HIV than patients without HIV.
  • In patients with extrapulmonary TB, common presentations include genitourinary tuberculosis, central nervous system TB, abdominal TB, TB lymphadenitis, and pleural TB.
• Mycobacterium tuberculosis infection may increase HIV replication and accelerate progression of HIV disease.

Evaluation

• Diagnosis of tuberculosis (TB) in patients with HIV is challenging due to high frequency of smear-negative cases, atypical radiographic presentation, and extrapulmonary manifestations.
• Suspect TB in patients with HIV and clinical manifestations consistent with TB infection, particularly those with residence or travel to TB-endemic regions or known exposure to TB.
• All patients with suspected TB should have chest x-ray early in the course of investigation (Strong recommendation).
  • Radiologic presentation of chest x-ray varies with state of immunodeficiency.
    • In patients with CD4 T-cell count > 350 cells/mm³, presentation may resemble that in patients uninfected with HIV including upper lobe infiltrates, cavitation, and pleural disease.
    • In patients with profound immunocompromise, cavitation is less common and x-ray findings may include pleural effusion, lower or middle lobe infiltrates, miliary infiltrates, mediastinal adenopathy, interstitial nodules, or normal x-ray.
  • Consider sputum smear and culture in symptomatic patients with normal chest x-rays.
• Additional diagnostic testing is directed at sites of disease.
  • For patients with suspected TB lymphadenitis, consider needle aspiration or biopsy for histopathology, acid fast bacilli, smear, and culture.
  • Sample pleural fluid, pericardial fluid, ascites, or cerebrospinal fluid (CSF) if there is evidence of involvement.
• Consider nucleic acid amplification tests in patients with advanced immunodeficiency, as testing is more rapid than culture, more sensitive than smear microscopy, and allows distinction between tuberculosis and nontuberculous mycobacterial infections.
• Lateral flow urine lipoarabinomannan (LF-LAM) may be used to assist diagnosis of TB in patients with HIV and CD4 T-cell count ≤ 100 cells/mcL or serious illness (Weak recommendation).
• Tuberculin skin tests and interferon gamma release assays (IGRAs) may be useful to corroborate diagnosis of TB if samples for smear and culture are difficult to obtain or are unrevealing, although tests do not distinguish between latent and active disease.

Management

• Start empiric treatment in patients with HIV and suspected tuberculosis (TB) until diagnostic work-up is complete (Strong recommendation).
  • CDC has issued guidance regarding use of rifampin and rifapentine for treatment of active and latent TB infection after some manufacturers detect nitrosamine impurities in their products.
  • Recommendations for antituberculosis treatment regimens in adults with HIV infection follow the same principles as for adults without HIV infection.
  • Initial phase consists of a 4-drug regimen of isoniazid (INH), rifampin (or rifabutin), pyrazinamide, and ethambutol daily for 2 months (Strong recommendation).
  • Continuation phase consists of a 2-drug regimen of INH plus rifampin (or rifabutin) daily for drug-susceptible TB (Strong recommendation).
  • Treatment duration varies by presentation:
    • 6 months for patients with drug-susceptible pulmonary TB (Weak recommendation)
    • 9 months for patients with severe cavitary disease, disseminated extrapulmonary disease, or positive sputum culture after 2 months of treatment (Weak recommendation)
    • 9-12 months for patients with central nervous system (CNS) involvement (Weak recommendation)
    • 6 months for patients with extrapulmonary TB in non-CNS sites (Weak recommendation)
  • Use of intermittent TB regimens in persons with HIV infection is associated with relapse and development of rifamycin resistance.
• Corticosteroids are recommended for patients with CNS disease (Strong recommendation).
• All patients should be given antiretroviral therapy (ART) (Strong recommendation):
  • The preferred cotreatment regimen includes rifampin-based TB therapy plus ART regimen of efavirenz plus 2 nucleoside analogs (Strong recommendation).
  • Alternative regimens include dual nucleoside analogs plus raltegravir 400-800 mg twice daily with standard rifampin dosing or dual nucleoside analogs plus ritonavir-boosted protease inhibitor with rifabutin-based TB therapy (Weak recommendation).
  • While rifamycins interact with many ART drugs, rifamycin should remain as part of the regimen unless the isolate is rifamycin-resistant or patient has severe adverse effects related to rifamycin (Strong recommendation).
  • Recommendations for timing of ART vary by CD4 T-cell count and clinical disease.
    • For patients with CD4 T-cell count < 50 cells/mcL, start ART within 2 weeks of starting TB treatment (Strong recommendation).
    • For patients with CD4 T-cell count ≥ 50 cells/mcL, start ART within 8 weeks of starting TB treatment (Strong recommendation).
    • For patients with tuberculous meningitis, exercise caution as high rates of adverse events and deaths have been reported with early initiation of ART (Strong recommendation).
    • For pregnant women, start ART as early as possible, both for maternal health and prevention of mother-to-child transmission (Strong recommendation).
• Patients with HIV infection and TB are at risk of developing immune reconstitution inflammatory syndrome (IRIS) with worsening of signs and symptoms after beginning antituberculosis and antiretroviral therapy.
  • Risk of IRIS is higher in those who start ART within 2 weeks of starting antituberculosis treatment compared to those who started at 8-12 weeks.
  • Most IRIS is self-limited and can be managed with anti-inflammatory agents; however in some instances corticosteroids may be needed to control symptoms (Weak recommendation).