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In HIV-infected tuberculosis patients with <200 CD4+ lymphocytes/mm3, highly active antiretroviral therapy (HAART) improves survival but can be complicated by immune reconstitution inflammatory syndrome (IRIS) and drug toxicity. We conducted a decision analysis in hypothetical cohorts of 1000 patients in which HAART was initiated during the first 2 months of tuberculosis therapy (early) or during months 2 through 6 of tuberculosis therapy (deferred) or was withheld until after tuberculosis therapy (no HAART). Outcomes assessed were 1-year mortality and the combined outcome of 1-year mortality, new AIDS-defining illness, severe IRIS, and severe drug toxicity. There were 33, 48, and 147 deaths and 497, 501, and 501 combined outcome events in the early HAART, deferred HAART, and no-HAART groups, respectively; most events were drug toxicity in the early and deferred groups and HIV-related mortality or AIDS-defining illness in the no-HAART group. In a 2-way sensitivity analysis of mortality, early HAART was favored, even with the highest reported rates of IRIS (70%) and severe drug toxicity (56%). Deferred HAART was favored over early HAART only if the IRIS-related mortality rate in the early group exceeded 4.6%. These results support early initiation of HAART in patients with AIDS, except when IRIS-related mortality rates are high.