AIDS Institute: Tuberculosis management for people with HIV

TUBERCULOSIS MANAGEMENT
FOR PEOPLE WITH HIV INFECTION

July, 1995

CONTENTS

Diagnosis

TB Prophylaxis

Treatment for Tuberculosis

Special Considerations (MDR-TB, Pregnant women)

Records andReporting

PPD Testing

Suggested Reading

Tuberculosis (TB) often develops as an opportunistic infection in people with HIV infection.The disease has been reported to occur in 5% to 21% of people with HIV infection. In certain areas of New York City, 50% to 80% of patients with active TB are HIV positive. Pulmonary TB and extrapulmonary TB are AIDS-defining illnesses for people with HIV infection.

People with TB infection who are HIV seropositive are more likely to develop tuberculosis than those who are HIV seronegative. For example, for those who have been infected with M. tuberculosis, the risk of active TB disease in the general population is 10% per lifetime, but the risk for a person with HIV is 8% per year. Recent data also suggest that people with HIV develop active TB disease more rapidly once infected, and that exogenous reinfection can occur. In addition, coinfection with M. tuberculosis and other mycobacterial species can occur.

Tuberculosis should be considered whenever patients infected with HIV develop unexplained pulmonary symptoms, fever, or weight loss. Diagnosis of TB in persons with HIV is difficult because: 1) atypical pulmonary disease occurs more often than classical apical cavitary disease; 2) normal chest X-rays have been reported in people with active pulmonary disease;and 3) extrapulmonary disease occurs more frequently. Chest X-rays must be supplemented by sputum AFB smears and cultures in all symptomatic patients. Some patients with HIV infection who have had sputum cultures positive for M. tuberculosis have had sputum smears negative for AFB. In addition, the AFB smear is less specific for diagnosis of pulmonary TB in the patient with HIVinfection, since cultures often yield mycobacterial species other than M. tuberculosis.

All persons with HIV infection should be tested using purified protein derivative (PPD).Tuberculin reactions of 5 mm or greater are considered positive for people with HIV infection. Since PPD testing may be unreliable in immunosuppressed patients with HIV, anergy testing should be performed at the same time. >

Antituberculous chemotherapy should be initiated whenever AFB are found on smear, pending culture results. Unexplained clinical or radiographic pulmonary disease in persons with HIV should prompt consideration of antituberculous therapy. The duration of both prophylaxis and therapy in most protocols is longer than for seronegative persons. >

Diagnosis

PPD TESTING (See PPD Testing protocol.)

All individuals with HIV infection who do not have a documented history of tuberculosis or a positive PPD test should be tested using PPD.
Inject 0.1 ml of 5TU PPD intradermally. Observe reaction in 48 to 72 hours. Skin tests should be read by trained medical personnel.
Reactions of 5 mm or greater of induration are considered positive in people who are HIVseropositive, and the millimeters of induration should be specifically recorded.
A negative PPD result does not exclude TB infection and cannot be interpreted without anergy testing.
Patients with HIV who were vaccinated with BCG should still be tested with PPD.
Results should be interpreted in the same way as for persons who are HIV seropositive and have not received BCG.

ANERGY TESTING

Patients with HIV should be evaluated for anergy. Absence of anergy validates a negative PPD test result.
Conduct anergy and PPD tests simultaneously in new patients.
The following two delayed-type hypersensitivity antigens should be used:

- Mumps antigen (0.1 cc of 40 CFU/ml). This solution is not the same product as the mumps vaccine.
- Tetanus toxoid (0.1 cc of 1:5 mixture of tetanus toxoid fluid and saline preparation. The tetanus toxoid fluid must be marked non alum absorbed. Once diluted, it has a refrigerated shelf life of 14 days).

When available, Candida antigen can be substituted for one of the above reagents.
Since tetanus toxoid is the most sensitive antigen to measure skintest reactivity, it should be included in the anergy panel when possible.
Any degree of induration constitutes a positive reaction.

EXTRAPULMONARY DISEASE

Patients with HIV often present with atypical forms of tuberculosis.
Mycobacterial blood cultures may be positive in extrapulmonary disease and should be performed.
Other tissue cultures and biopsies may be necessary, depending on the suspected site of the disease.
Obtain sputum cultures in patients with extrapulmonary disease, even in the absence of pulmonary symptoms.
Persons who do not have pulmonary disease are not contagious through airborne exposure.

TB Prophylaxis

WHO SHOULD RECEIVE PROPHYLAXIS

Begin prophylaxis in patients infected with HIV who are PPD positive (or who have a history of positive PPD) if they have not already received prophylaxis, regardless of age.
Consider prophylaxis in anergic patients who are members of communities in which the prevalence of TB infection is >10%, such as prisoners, the homeless, migrant laborers, people with a history of intravenous drug use, and people from Southeast Asia, Africa, or Latin America.

THERAPEUTIC CONSIDERATIONS

Isoniazid (INH) regimens of 300 mg orally once daily or 900 mg orally twice weekly are adequate for individuals exposed to INH-sensitive tuberculosis.
Pyridoxine therapy at doses of 25 mg orally once daily is useful for the prevention of peripheral neuropathy.
Duration of prophylaxis should be at least 1 year.
Consult with an infectious disease or pulmonary specialist to determine drug regimen if the patient has been exposed to a drug-resistant strain of tuberculosis.
Monitor adherence to the prophylactic regimen, and refer patients to a Directly Observed Preventive Therapy (DOPT) program if adherence may be difficult. Currently, the only available programs are in New York City. Call 212-788-4373 for program information.

MONITORING FOR ISONIAZID TOXICITY

Patients should be educated about the signs and symptoms of clinical liver disease.
Baseline liver function tests (serum ALT/AST) should be performed in all patients before initiating INH therapy.
Liver function tests should be performed more frequently in patients with elevated baseline values and in those with underlying liver disease.
Liver function tests should be repeated if there are clinical signs of liver disease.
INH should be discontinued when liver enzymes (ALT/AST) exceed 3 to 5 times baseline or in patients who develop symptoms of hepatitis.

Treatment for Tuberculosis

INDICATIONS FOR TREATMENT

Initiate chemotherapy against M. tuberculosis whenever AFB, of which the species has not yet been determined, are seen in sputum or in a specimen from any sterile site.
Consider initiation of antituberculous therapy in patients who are HIV seropositive with unexplained clinical or radiographic pulmonary disease.

THERAPEUTIC CONSIDERATIONS

Respiratory isolation must be maintained during in-hospital treatment until the patient with pulmonary tuberculosis is no longer infectious.
Tailor initial drug regimens to patterns of susceptibility in the particular institution or neighborhood.
Rapid diagnostic techniques for identification and susceptibility should be utilized if possible. If these are not available, the New York State Department of Health Wadsworth Center for Laboratories and Research has a fast track system that uses rapid culture techniques for diagnostic cultures if arrangements are made by the referring hospital. Information about this program is available at (518) 474-2196.
Perform drug susceptibility tests.
Include at least four drugs in the initial therapy, even if INH or multi-drug resistance is not suspected. Adjust when results of drug susceptibility tests are available.

For drug-sensitive disease, use:

Isoniazid 300 mg/day with pyridoxine 25 mg/day;
Rifampin 600 mg/day;
Pyrazinamide (PZA) 20-30 mg/kg/day, not to exceed 2 grams/day (can be discontinued after 2 months if organism is sensitive to INH and rifampin); and
Ethambutol 15-25 mg/kg/day (can be discontinued if organism is found to be sensitive to INH and rifampin).

For suspected INH or multidrug-resistant disease:

Begin initial therapy according to prevailing institutional guidelines and refer to a specialist.

Fixed-dose drug combination preparations (INH/rifampin/pyrazinamide) promote compliance with treatment. Regimens must contain bio-available preparations of rifampin. Dosage regimens must be checked carefully to determine the number of pills that patients must take.

MONITORING FOR COMPLETION AND INTERACTIONS

Duration of therapy for drug-sensitive disease should be at least 9 months and at least 6 months after cultures have become sterile, whichever is longer.
Smears and cultures should be performed monthly at least until cultures are negative. Persistence of positive smears after 2 months should raise possibility of drug resistance, inappropriate regimen, or noncompliance.
Rifampin interacts with methadone, requiring an increase of up to 50% of the methadone dose.
Rifampin may cause standard doses of oral contraceptives to be ineffective and may also necessitate increasing the required dose of many other drugs that are metabolized in the liver, such as phenytoin, fluconazole, and clarithromycin.
Inform patients that rifampin turns urine, tears, and other body fluids orange, and will stain contact lenses.
Monitor for signs of INH toxicity as above.
Monitor adherence to the regimen. This may require Directly Observed Therapy (DOT). In New York City, information on available programs can be obtained by calling 212-553-4256. In other counties, the local Department of Health should be contacted. In New York City, the Commissioner of Health has regulatory authority to mandate that a patient take TB medication. If compliance remains inadequate, detention can be ordered. These steps should be considered only when all other efforts to encourage adherence have failed.

(Information about Commissioner's Orders for Treatment and Detention can be obtained at 212-553-4288.)

Special Considerations

MULTIDRUG-RESISTANT TUBERCULOSIS (MDRTB)

Strains of M. tuberculosis resistant to multiple antibiotics, including INH, rifampin, ethambutol, and streptomycin, were reported with increasing frequency in New York State in the early 1990's. Greater adherence to TB control methods has resulted in a decreasing incidence of multiple-drug-resistant TB (MDRTB).
Factors associated with MDRTB include:

Prior intermittent or incomplete antituberculous drug therapy;
Exposure to a patient with known MDR tuberculosis;
Sporadic health care;
History of intravenous substance use;
Homelessness; and
History of incarceration.

Tailor therapeutic regimens for MDRTB according to drug susceptibility patterns within a particular facility, neighborhood, or site of exposure.
Consult an infectious diseases or pulmonary specialist.
Treatment should be for at least 18 months. Many clinicians treat for 2 years. Smears and cultures should be continued for duration of treatment in the case of MDRTB.
Arrange follow-up care, which should include directly observed therapy.

PREGNANT WOMEN

Pregnant women with a newly positive PPD should have a chest X-ray (with a lead apron abdominal shield) to exclude tuberculosis.
Pregnant women with HIV infection who have a positive PPD skin-test with a normal chest X-ray should receive INH prophylaxis after the first trimester.
Pregnant women who are taking INH should have liver function tests (serum AST/ALT) monthly.
Treatment regimens for pregnant women with active tuberculosis should be decided in consultation with an infectious diseases or pulmonary specialist.
Streptomycin is contraindicated during pregnancy.

Records and Reporting

Report suspected or diagnosed cases of tuberculosis to local health officials in accordance with Title 10 NYCRR 2.1 and 2.10.
Records should include:

Dates of skin tests with measurements of induration in millimeters;
Date of known exposure to tuberculosis;
Prior history of TB disease and treatment;
Date and results of chest X-ray examinations;
Date, results, and source of culture and sensitivity testing; and
Dates of initiation and completion of therapy.

If TB history is not known for a patient, the local Department of Health may have patient-based information available for clinicians. To report a TB case or obtain information on TB patients in New York City, call the New York City Department of Health Bureau of TB Control's TB Registry at (212) 788-4162. The local Department of Health should be called outside of New York City.

PPD TESTING

1. Perform PPD and anergy tests.

PPD POSITIVE: Obtain chest X-ray. Go to step 2a or 2b.

PPD Negative/NOT ANERGIC:

Repeat PPD test in 1 year, unless screening is prompted by known exposure, in which case PPD should be repeated in 3 months.
For patients who have frequent exposure to individuals with suspected or confirmed tuberculosis, PPD testing should be performed every 6 months.

PPD Negative/ANERGIC: Go to step 2a or 2c.

2. Obtain Chest X-Ray, PA and lateral views.

a) If the chest X-ray reveals apulmonary infiltrate:

Obtain sputum for AFB smear culture (3 specimens on separate days).
Evaluate need for immediate therapy.
Obtain consultation with infectious diseases (ID) or pulmonary specialist.
If patient is PPD positive and pulmonary TB is ruled out, proceed to step 2b.
If patient is anergic and TB disease is ruled out, proceed to step 3.

b) If the chest X-ray is normal and the patient is PPD POSITIVE:

Evaluate for the presence of extrapulmonary disease.
Treat with isoniazid (INH) for 1 year: INH 300 mg po qd or INH 900 mg po biw. Consider need for DOPT.
Consult ID or pulmonary specialist to select an appropriate regimen, if exposure to drug-resistant organisms is suspected.

c) If the chest X-ray is normal and the patient is ANERGIC: