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Background:  Immune reconstitution engendered by HAART has led to significant decreases in the incidence of opportunistic infections in adults and children. Withdrawal of what was once considered indefinite antimicrobial prophylaxis against opportunistic pathogens has been safely and successfully accomplished in HIV-infected adults achieving elevations in CD4 counts to levels >250 cells/mm³. In this prospective observational study we investigated the incidence of serious bacterial infections and other opportunistic infections in children and adolescents who had achieved immunologic reconstitution and had their opportunistic infection prophylaxis withdrawn.

Methods:  HIV-infected children (2 to 21 years) were enrolled in PACTG protocol 1008 if they had met the indications for and received PCP prophylaxis for >6 months, but had a sustained response to HAART with CD4 cells >20% for patients >6years or CD4 cells >25% for patients 2 to 6 years for ≥16 weeks. PCP and MAC prophylactic drugs were discontinued at the time of entry into the study. Patients were taken off observation and opportunistic infection prophylaxis reinstituted (as clinically indicated) if they experienced any opportunistic infection, a second serious bacterial infection or their CD4 cell count fell below 15%.

Results:  We observed 235 patients with a median age of 9 years for a median duration of 30.4 months (range of 1 to 37.5 months), yielding 547 patient-years of observation. Median CD4% at baseline was 31%. 19 pts experienced a total of 20 serious bacterial infections for a rate of 3.7 serious bacterial infections /100 patient-years (95%CI:  2.2, 5.7). The majority (80%) of serious bacterial infection events were presumed bacterial pneumonia (abnormal CXR and clinical symptoms), although 4 patients had proven bacterial serious bacterial infections:  2 with pneumococcal bacteremia and 1 each with group A streptococcal pneumonia and H. influenzae type B epiglottitis. There were no documented infections due to PCP or disseminated MAC. There were 2 non-opportunistic infection-related deaths, and 16 patients were discontinued when their CD4% declining <15%. There were no specific factors to distinguish patients who experienced a serious bacterial infection from those who did not including age, sex, race, CD4 count at baseline, duration of time since attaining a CD4 count of 15%, use of HAART regimen at baseline, or immunologic response to a neoantigen (hepatitis A vaccine).

Conclusions:  Withdrawal of opportunistic infection prophylaxis in HIV-infected children results in a low rate of serious bacterial infections in children followed for as long as 3 years. Consistent with the experience in adults opportunistic infection prophylaxis can be safely discontinued in children >2 years of age who have achieved persistent immunologic reconstitution.

Keywords: Withdrawal of Prophylaxis; Serious Bacterial Infections; Pediatric HIV Infection