Tuberculosis
Rationale and Background
Tuberculosis (TB) is a significant cause of morbidity and mortality in HIV-infected patients. The risk of developing active TB in patients with HIV disease if infected with Mycobacterium tuberculosis is approximately 10 percent each year compared to a 10 percent lifetime risk in immunocompetent hosts.Antimicrobial prophylaxis is effective in HIV-infected patients with a positive TB skin test; antimicrobial treatment is effective in those with active TB.
TB may present with extrapulmonary manifestations in advanced HIV disease, and cutaneous anergy (lack of reactivity to skin tests) is more common in this context. Diagnosis may be delayed because of these characteristics.
Multidrug-resistant (MDR) strains, which are problematic to treat, have become common in some parts of the country.
Screening
Screening for TB should be part of the initial assessment of HIV-infected patients and repeated annually in high risk individuals if the test result is negative.Testing is performed with PPD (purified protein derivative [intermediate strength, 5TU]) administered intracutaneously and read at 48-72 hours. The routine use of control agents, such as candida, tetanus toxoid, and mumps, is not recommended because of their lack of standardization. A positive test in an HIV-infected patient is defined as 5 mm or more of induration. A history of prior BCG administration should not affect the interpretation of PPD results.
Prophylaxis
Prophylactic antimicrobial therapy is recommended for HIV-infected patients regardless of age with any of the following:
- positive PPD
- history of a positive PPD and no documentation of a standard course of prophylaxis
- exposure to active pulmonary tuberculosis
Prophylaxis is not generally recommended in HIV-infected persons with anergy who have historical risk factors for TB exposure, such as injection drug use, alcoholism, homelessness, incarceration, living in shelter or institution, and originating from a country endemic for TB.
A chest x-ray should be performed on all patients with a positive PPD before initiating antimicrobial prophylaxis to rule out active pulmonary TB. If extrapulmonary disease is suspected clinically, the appropriate additional diagnostic evaluation should also be completed.
Isoniazid (INH) 300 mg po qd given with pyridoxine 50 mg po qd in those with history of alcoholism or nutritional deficiency or directly observed therapy (DOT) of INH 900 mg plus pyridoxine 100 mg twice weekly is the standard prophylactic regimen. Treatment is continued for nine months.
Hepatotoxicity to INH increases is uncommon in patients younger than 35 years old but increases with advancing age. Other common side effects include fever and rash. The drug should be discontinued if clinical stigmata of hepatitis develop or if liver transaminases increase to > 5 times baseline.
Rifampin (RIF) 600 mg po qd or rifabutin 300 mg po qd x four months are alternative prophylactic regimens. Short course therapy using pyrazinamide (PZA) in combination with rifampin should be avoided because of reports of severe hepatotoxicity.
Infectious disease consultation is recommended in the prophylaxis of MDR TB strains.
Treatment
A four drug regimen is preferred for initial empiric treatment of TB pending culture and sensitivity results. It should include INH, RIF, PZA plus streptomycin or ethambutol unless the strain is known to be MDR. Duration of treatment is generally six to twelve months.DOT is preferred over conventional management whenever possible. All patients with INH-resistant or rifampin-resistant isolates, as well as persons with a history of nonadherence, should receive DOT.
Rifampin, an important component of combination therapy for TB, cannot be given with protease inhibitors (PIs). RIF-containing treatment regimens for TB should completed before initiating or resuming PI therapy or, in some instances, rifabutin can be substituted for it.
Susceptibility tests should be performed on the initial TB isolate and on any isolate obtained at 3 months post-treatment.Antimicrobial drug resistance should be considered if there has been prior ineffective or intermittent treatment or if there is a history of exposure to TB strains from Central or South America, Africa, or the Far East.
Infectious disease consultation is recommended in the treatment of active TB.
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Comments about these guidelines are welcome and can be sent to the author at hlibman@caregroup.harvard.edu