Tuberculosis in HIV

Essentials of Diagnosis

• Fatigue, weight loss, fever, night sweats, and cough

• Pulmonary infiltrates on chest radiograph, most often apical

• Positive tuberculin skin test reaction (most cases)

• Smear of sputum positive for acid-fast bacilli or culture of sputum positive for Mycobacterium tuberculosis (MTB)

General Considerations

• Latent tuberculosis infection (LTBI) occurs when bacilli are contained within granulomata, the typical response to infection in immunocompetent persons

  • Nontransmissible, but may become active disease if a person's immune function becomes impaired

  • Reactivation occurs within 2 years in up to 50% of HIV-positive patients

• Medication nonadherence is a major cause of treatment failure, disease transmission, and development of drug resistance

• Resistance may be to single or multiple drugs

  • Drug-resistant TB is resistant to one first-line antituberculous drug, either isoniazid or rifampin

  • Multidrug-resistant tuberculosis (MDR-TB) is resistant to isoniazid and rifampin, and possibly additional agents

  • Extensively drug-resistant tuberculosis (XDR-TB) is resistant to isoniazid, rifampin, fluoroquinolones and either aminoglycosides or capreomycin or both

Demographics

• HIV increases the risk of reactivation tuberculosis

• Risk factors for drug resistance include

  • Immigration from a region with drug-resistant tuberculosis

  • Close contact with a patient infected with drug-resistant tuberculosis

  • Unsuccessful prior therapy

  • Patient noncompliance

Symptoms and Signs

• Cough is most common

• Blood-streaked sputum is common, frank hemoptysis is rare

• Slowly progressive constitutional symptoms

  • Malaise

  • Anorexia

  • Weight loss

  • Fever

  • Night sweats

• Patients appear chronically ill and malnourished

• Chest examination is nonspecific; post-tussive apical rales are classic

• Extrapulmonary disease is especially common, often with lymphadenitis or miliary disease

• Atypical presentations are common

Differential Diagnosis

• Pneumonia or lung abscess

• Lung cancer

• Lymphoma

• Mycobacterium avium complex (or other nontuberculous mycobacteria)

• Sarcoidosis

• Fungal infection, eg, histoplasmosis

• Endocarditis

• Nocardiosis

Laboratory Tests

• Tuberculin skin test (TST)

  • The Mantoux test is the preferred method: 0.1 mL of purified protein derivative (PPD) containing 5 tuberculin units is injected intradermally on the volar surface of the forearm using a 27-gauge needle on a tuberculin syringe. After 48–72 hours, the transverse width in millimeters of induration at the skin test site is measured

  • Table 9–13 summarizes the criteria established by the Centers for Disease Control and Prevention (CDC) for interpretation of the Mantoux TST

• Interferon gamma release assays (IGRAs) (including the QuantiFERON and T-SPOT tests) are in vitro assays of CD4+ T-cell-mediated interferon gamma release in response to stimulation by specific M tuberculosis antigens

  • In endemic areas, IGRAs are no more sensitive than the TST in active tuberculosis (20–40% false-negative rate) and cannot distinguish active from latent disease

  • IGRAs should not be used to exclude active tuberculosis

Imaging Studies

• In early HIV disease, radiographic features resemble those of tuberculosis patients who do not have HIV disease

• Atypical radiographic features seen in late HIV infection include

  • Lower lung infiltrates

  • Diffuse or miliary infiltrates

  • Pleural effusions

  • Hilar and lymph node involvement

  • Mediastinal lymph nodes

Diagnostic Procedures

• Sputum induction is required for patients unable to voluntarily produce a sample

• Bronchoscopy may be considered in smear-negative patients in whom there is a high suspicion of disease

Medications

• See Tables 9–14 and 9–15

• For best response, treat HIV infection and tuberculosis concurrently; prolonged antituberculous therapy may be warranted

• Multiple drugs to which the organism is susceptible are used

• At least two new antituberculosis drugs are added when treatment failure is suspected

• If a twice- or thrice-weekly regimen is used, then dosages are increased (Table 9–15)

• Treatment is similar to treatment of tuberculosis in HIV-negative patients, with the following additional considerations

  • Directly observed therapy (DOT) is indicated for all HIV-positive patients

  • Duration of therapy is longer

  • Drug interactions occur between rifampin or rifabutin and protease inhibitors or nonnucleoside reverse transcriptase inhibitors

  • Pyridoxine (10–50 mg once daily orally) should be given to all HIV-positive patients taking isoniazid to reduce nervous system side effects

• Extrapulmonary disease

  • In most cases, regimens effective for pulmonary disease are adequate

  • Miliary, meningeal, bone, or joint involvement require 9 months of therapy

  • Corticosteroids reduce complications of tuberculous pericarditis and meningitis

Surgery

• Early débridement and drainage are recommended for skeletal tuberculosis

Therapeutic Procedures

• Needle biopsy of the pleura reveals granulomatous inflammation in 60% of patients with tuberculous pleural effusions

• Culture of three pleural biopsy specimens combined with microscopic examination increases the diagnostic yield to 90%

• Complete blood count, pulmonary function tests, blood urea nitrogen, and serum creatinine should be checked at baseline

• Visual acuity and red-green color vision testing before initiating ethambutol

• Audiometry prior to streptomycin therapy

• Routine monitoring for evidence of drug toxicity is not recommended

Follow-Up

• Monthly visits are recommended for outpatients

• Monthly sputum smears and cultures should be done until documented negative

• Patients with negative sputum after 2 months of therapy should have smear and culture repeated at the end of therapy

• Patients whose cultures do not turn negative or who have persistent symptoms after 3 months of therapy should be evaluated for MDR-TB

• Patients with MDR-TB should have sputum smear and culture monthly throughout therapy

• Chest radiograph is recommended at conclusion of successful therapy

Complications

• Development of drug resistance

• Potential drug toxicities

  • Loss of visual acuity or development of red-green colorblindness with ethambutol

  • Hearing loss with streptomycin

Prevention

• Despite a negative purified protein derivative (PPD) skin test, HIV-positive patients who are close contacts of patients with active MTB should receive 12 months of preventive therapy (see Tuberculosis, Latent Infection)

• HIV-positive patients with positive PPD skin tests but without active MTB should be treated (see Tuberculosis, Latent Infection)

• All suspected and confirmed cases of MTB should be reported to local and state public health authorities

When to Refer

• All cases of drug-resistant tuberculosis

• All cases of tuberculosis in HIV-positive patients

• DOT is recommended for all patients with MDRTB and those receiving twice- or thrice-weekly therapy

When to Admit

• Hospitalization is not necessary for initial therapy in most patients

• Admit patients who are incapable of self-care or likely to expose susceptible individuals to tuberculosis

• Hospitalized patients require isolation in appropriately ventilated rooms until three sputums from different days are negative for MTB organisms