Active Tuberculosis

Clinical and Public Health Principles
Prompt initiation of effective antituberculosis treatment increases the probability that a patient with HIV infection who develops TB will be cured of this disease (45,131). TB treatment also quickly renders patients noninfectious (30), with the resulting reduction in the amount of M. tuberculosis transmitted to others, and it minimizes the patient's risk of death resulting from TB (41-43,132). Therefore, clinicians must immediately and thoroughly investigate the possibility of TB when a patient infected with HIV has symptoms consistent with TB. Persons suspected of having current TB disease should immediately be started on appropriate treatment, ideally with directly observed therapy (DOT) (133-135), and placed in TB isolation as necessary (136,137). Patients with TB and unknown HIV-infection status should be counseled and offered HIV testing. HIV-infected patients undergoing treatment for TB should be evaluated for antiretroviral therapy. Most patients with HIV-related TB are candidates for concurrent administration of antituberculosis and antiretroviral drug therapies (4).

Health-care providers, administrators, and TB controllers must strive to promote coordinated care for patients with TB and HIV and remove existing barriers to information-sharing between TB control programs and HIV/AIDS programs. TB control programs are responsible for setting TB treatment standards for physicians in the community, promoting the awareness and use of recommended TB infection-control practices, and enforcing state and local health department requirements concerning TB case notification and early reporting of drug-susceptibility test results. Because of the complexity of managing HIV-related TB disease and the serious public health consequences of mismanagement, care for persons with HIV-related TB should be provided by, or in consultation with, experts in the management of both TB and HIV disease.

Diagnosis of HIV-Related Tuberculosis
The typical signs and symptoms of pulmonary TB are cough with or without fever, night sweats, weight loss, and upper-lobe infiltrates with or without cavitation on chest x-rays. The diagnosis of TB for some HIV-infected patients might be difficult because TB in an immunocompromised host can be associated with atypical symptoms, a lack of typical symptoms, and a paucity of findings in chest x-rays (138-140). Among persons with AIDS, the diagnosis of TB also can be complicated by the presence of other pulmonary infections such as Pneumocystis carinii pneumonia and Mycobacterium avium complex disease and by the occurrence of TB in extrapulmonary sites. For patients with unusual clinical and radiographic findings, the starting point for diagnosing active TB often is a positive tuberculin skin test (TST). All patients with positive TSTs should be evaluated to rule out active TB (see Diagnosis of M. tuberculosis Infection Among HIV-Infected Persons).

Medical Evaluation of Patients Suspected of Having Active TB

Rating Recommendation
A.II Every person suspected of having TB should undergo a thorough medical evaluation (see Box 1(Table_B1)).

A.II The evaluation should include HIV counseling and testing unless the person has documentation of a) a positive HIV antibody test or b) a negative result to an HIV antibody test conducted within the past 6 months.

Management of HIV-Infected Patients with Active TB Coadministration of TB Treatment and Antiretroviral Therapy
The following management strategies are for patients with HIV-related pulmonary TB a) who are not known to have or who do not have risk factors for multidrug-resistant TB and b) for whom antiretroviral therapy is appropriate. When they first receive care for active TB disease, some patients might already be receiving antiretroviral therapy, whereas other patients might be newly diagnosed with HIV infection (Figure_1). For these newly diagnosed patients, in addition to the currently established recommendations for the immediate initiation of antituberculosis therapy, recently published guidelines (4) recommend the use of antiretroviral therapy. When treatments for HIV and TB disease are begun simultaneously, the optimal setting is one with experienced and coordinated care givers as well as accessible resources to provide a continuum of medical services (e.g., a reliable source of medications and social, psychosocial, and nutritional services).

Because of drug interactions, the use of rifampin to treat TB is not recommended for patients who a) will start treatment with an antiretroviral regimen that includes a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor (NNRTI) at the same time they begin treatment for TB (4) or b) have established HIV infection that is being maintained on such an antiretroviral regimen when TB is newly diagnosed and needs to be treated. Thus, two TB treatment options are currently recommended for these patients: a) a rifabutin-based regimen or b) an alternative nonrifamycin regimen that includes streptomycin (see Treatment Options for Patients with HIV Infection and Drug-Susceptible Pulmonary TB and Figure_1). Using a rifampin-based TB treatment regimen continues to be recommended for patients with HIV infection a. who have not started antiretroviral therapy, when both the patient and the clinician agree that waiting to start such therapy would be prudent or b) for whom antiretroviral management does not include a protease inhibitor or an NNRTI (4) (Figure_1).

When determining the time to begin antiretroviral therapy for patients who are acutely ill with TB, clinicians and patients need to consider the existing clinical issues (e.g., drug interactions and toxicities, ability to adhere to two complex treatment regimens, and laboratory abnormalities). A staggered initiation of antituberculosis and antiretroviral treatments for patients not currently on antiretroviral therapy might promote greater adherence to the TB and HIV treatment regimens and reduce the associated drug toxicity of both regimens. This strategy might include starting antiretroviral therapy either at the end of the 2-month induction phase of TB therapy or after TB therapy is completed. When a decision is made to delay initiation of antiretroviral therapy, clinicians should monitor the patient's condition by measuring plasma HIV RNA levels (viral load) and CD4+ T-cell counts and assessing the HIV-associated clinical condition at least every 3 months (4), because such information will assist in decisions regarding the timing for initiating such therapy. For some patients, switching from a rifampin-based TB regimen to either a rifabutin-based or a nonrifamycin-based TB regimen will be necessary if the decision is made to start antiretroviral therapy before completion of antituberculosis therapy. Clinicians and patients should be aware that the potent effect of rifampin as a CYP450 inducer (77,80), which lowers the serum concentration of protease inhibitors and NNRTIs, continues up to at least 2 weeks following the discontinuation of rifampin. Thus, they should consider planning for a 2-week period between the last dose of rifampin and the first dose of protease inhibitors or NNRTIs (see TB Drug Interaction and Absorption and Table 1A of Appendix).

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