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Although the incidence of Pneumocystis carinii pneumonia (PCP) has declined, mortality of patients who require intensive care for this disease remains high. Highly active antiretroviral therapy (HAART) might alter the course of PCP either via effects on the immune system or through anti-Pneumocystis actions; however, HAART has not been studied in patients acutely ill with PCP.To assess the effects of HAART on outcome of patients admitted to the intensive care unit (ICU) with PCP.Retrospective cohort study carried out at a University-affiliated county hospital.Fifty-eight HIV-infected adults with PCP admitted to an ICU from 1996 to 2001.A standardized chart review was performed to collect information on demographic variables, hospital course, and use of antiretroviral therapy. Outcome measured was death while in the ICU or hospital.A total of 20.7% of patients were either receiving HAART or were started on therapy while hospitalized. Mortality in this group was 25%, whereas mortality in those not receiving therapy was 63% (P = 0.03). Multiple logistic regression analyses adjusting for potential confounders showed that HAART started either before or during hospitalization was associated with a lower mortality [odds ratio (OR), 0.14; 95% confidence interval (95% CI), 0.02–0.84; P = 0.03). The need for mechanical ventilation and/or development of a pneumothorax (OR, 20.9; 95% CI, 1.9–227.2; P = 0.01) and delayed ICU admission (OR, 9.7; 95% CI, 2.2–42.1; P = 0.002) were associated with increased mortality.Use of HAART is an independent predictor of decreased mortality in severe PCP and may represent a potential therapy to improve outcome in this disease.