New guidelines from the Centers for Disease Control and Prevention (CDC) outline the proper evaluation and treatment of tuberculosis in individuals infected with human immunodeficiency virus (HIV). These guidelines update previous CDC recommendations for the diagnosis, treatment and prevention of tuberculosis in adults and children infected with HIV. The new guidelines were published in the October 30, 1998, issue of the recommendations and reports series of Morbidity and Mortality Weekly Report. The CDC staff member who prepared this report is M. Elsa Villarino, M.D., M.P.H., Division of TB Elimination, National Center for HIV, STD and TB Prevention.
The report emphasizes that all HIV-infected persons should be screened for tuberculosis and, if they are found to be infected with tuberculosis, they should be treated to prevent the development of active tuberculosis disease. Early diagnosis and effective treatment of tuberculosis in persons with HIV infection are critical for curing tuberculosis, minimizing the negative effects of tuberculosis on the course of HIV disease and eliminating the spread of Mycobacterium tuberculosis. All patients suspected of having tuberculosis should undergo a thorough medical evaluation, including HIV counseling and testing, unless the person has documentation of HIV testing within the past six months. The report notes that because HIV infection so severely weakens the immune system, persons infected with both HIV and tuberculosis have a 100 times greater risk of developing active tuberculosis disease and becoming infectious to others, compared with persons who have tuberculosis but who are not infected with HIV.
According to the guidelines, one main consideration in persons coinfected with tuberculosis and HIV is to avoid the use of rifampin in combination with protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rifampin can seriously decrease the effectiveness of these therapies. Two treatment options currently recommended for these patients are (1) a rifabutin-based regimen or (2) an alternative non-rifamycin regimen that includes streptomycin. Rifabutin provides the first alternative treatment to rifampin. Previously, patients had to stop taking their HIV medication until tuberculosis therapy could be completed.
Because of potential side effects and concerns about drug resistance, health care professionals should provide directly observed therapy (DOT) to HIV-infected individuals and carefully monitor them for adverse effects and progress. Other strategies to promote adherence to drug regimens should also be implemented.
The following are the treatment options for patients with HIV infection and drug-susceptible pulmonary tuberculosis that have been excerpted from the document. The letters within parentheses following the recommendation designate the strength of the recommendation: A = strong, should always be offered; B = moderate, should usually be offered; C = optional; D = should generally not be offered; and E = should never be offered. The roman numerals within the parentheses indicate the quality of evidence supporting the recommendation: I = at least one randomized trial with clinical end points; II = clinical trials with laboratory end points only or conducted only in populations not infected with HIV; III = expert opinion.
DOT and other strategies that promote adherence to therapy should be used for all patients with HIV-related tuberculosis. (A-II)
For patients who are receiving therapy with protease inhibitors or NNRTIs, the initial phase of a six-month tuberculosis regimen consists of isoniazid, rifabutin pyrazinamide and ethambutol. These drugs are administered (1) daily for eight weeks or (2) daily for at least the first two weeks, followed by twice-a-week dosing for six weeks, to complete the two-month induction phase. The second phase of treatment consists of isoniazid and rifabutin administered daily or twice a week for four months. (A-II)
For patients in whom the use of rifamycins is limited or contraindicated for any reason (e.g., intolerance to rifamycins, patient/clinician decision not to combine antiretroviral therapy with rifabutin), the initial phase of a nine-month tuberculosis regimen consists of isoniazid, streptomycin, pyrazinamide and ethambutol administered either (1) daily for eight weeks or (2) daily for at least the first two weeks, followed by twice-a-week dosing for six weeks, to complete the two-month induction phase. The second phase of treatment consists of isoniazid, streptomycin and pyrazinamide administered two to three times a week for seven months. (Every effort should be made to continue administering streptomycin for the total duration of treatment or for at least four months after culture conversion. Some experts suggest that in situations in which streptomycin is not included in the regimen for all of the recommended nine months, ethambutol should be added to the regimen to replace streptomycin, and the duration of treatment should be prolonged from nine months to 12 months. Alternatives to streptomycin are the injectable drugs amikacin, kanamycin and capreomycin.) (B-II)
For patients who are not candidates for antiretroviral therapy, or for those patients for whom a decision is made not to combine the initiation of antiretroviral therapy with tuberculosis therapy, the preferred option continues to be a six-month regimen that consists of isoniazid, rifampin, pyrazinamide and ethambutol (or streptomycin). These drugs are administered either (1) daily for eight weeks or (2) daily for at least the first two weeks, followed by two to three times per week dosing for six weeks, to complete the two-month induction phase. The second phase of treatment consists of isoniazid and rifampin administered daily or two to three times a week for four months. Isoniazid, rifampin, pyrazinamide and ethambutol (or streptomycin) also can be administered three times a week for six months. (A-I)
Tuberculosis regimens consisting of isoniazid, ethambutol and pyrazinamide (i.e., three-drug regimens that do not contain a rifamycin, an aminoglycoside [e.g., streptomycin, amikacin, kanamycin] or capreomycin) should generally not be used for the treatment of HIV-infected patients with tuberculosis; if these regimens are used for the treatment of tuberculosis, the minimum duration of therapy should be 18 months (or 12 months after documented culture conversion). (D-II)
Pyridoxine (vitamin B6), 25 to 50 mg daily or 50 to 100 mg twice weekly, should be administered to all HIV-infected patients who are undergoing tuberculosis treatment with isoniazid, to reduce the occurrence of isoniazid-induced side effects in the central and peripheral nervous system. (A-II)
Because the CDC's most recent recommendations for the use of antiretroviral therapy strongly advise against interruptions of therapy (to minimize the emergence of drug-resistant HIV strains, if any antiretroviral medication must be temporarily discontinued for any reason, clinicians and patients should be aware of the theoretical advantage of stopping all antiretroviral agents simultaneously, rather than continuing the administration of one or two of these agents alone), and because alternative tuberculosis treatments that do not contain rifampin are available, previous antituberculosis therapy options that involved stopping protease inhibitor therapy to allow the use of rifampin are no longer recommended. (E-II)
The report also covers the following topics: management strategies; appropriate doses of medication; duration of tuberculosis treatment; the medical evaluation while receiving treatment for both tuberculosis and HIV infection; the treatment of tuberculosis in special situations, such as pregnancy; and tuberculosis preventive therapy regimens.