Fast track — ArticlesDiscontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection
Introduction
Several studies published in the past year have reported substantial decreases in morbidity, hospital admissions, and mortality among HIV-1-infected people, which were temporally associated with the introduction and widespread clinical use of increasingly intensive antiretroviral therapies, including protease inhibitors.1, 2, 3, 4, 5, 6 One US study of patients with advanced HIV-1 infection showed sharp declines in incidence of several serious opportunistic infections, including Pneumocystis carinii pneumonia (PCP). The rates of PCP became lower than at any time before the introduction of highly active antiretroviral therapy (HAART), whereas the use of PCP prophylaxis remained essentially constant. This finding suggests that HAART may confer a degree of protection against PCP over and above that of infection-specific prophylaxis. We assessed whether PCP prophylaxis in patients on HAART can be discontinued without increased risk of PCP, which was suggested by the preliminary results of one randomised clinical trial,7 and several small observational studies8, 9, 10 with short follow-up.
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Patients and methods
All patients were enrolled in the EuroSIDA study,11 a continuing prospective study of patients with HIV-1 infection in 52 centres across Europe and Israel. Centres provide data on three cohorts of patients of predefined numbers, each consisting of consecutive patients seen in the outpatient clinic. Eligible patients were those with CD4-lymphocyte counts of less than 500 cells/μL and age older than 16 years at enrolment. Information was collected from patients' case notes on standard
Results
7333 patients had been enrolled in the EuroSIDA study when we did our analysis, with a median of 16 months of follow-up (IQR 11–30) and 12 780 person-years of follow-up. Among those who did not die, about 5% of patients were lost to follow-up per year. A subset of 4990 (68%) patients had ever received PCP prophylaxis. By the end of our study, 3047 patients receiving PCP prophylaxis had started HAART. Of these, 2568 (84%) were taking primary PCP prophylaxis and 479 secondary prophylaxis (16%)
Discussion
HAART can help to suppress HIV-I replication and raise CD4-lymphocyte counts. In addition, use of HAART has led to a steep decline in HIV-1-associated opportunistic infections, death,1, 2, 3, 4, 5, 6 and resolution of various opportunistic infections.16, 17, 18, 19 HAART has also improved the specific CD4-T-cell reactivity against common opportunistic pathogens such as cytomegalovirus and Mycobaerium tuberculosis.20, 21 Taken together, these observations show at least partial restoration of
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