Published online March 16, 2005
PEDIATRICS Vol. 115 No. 4 April 2005, pp. e488-e494 (doi:10.1542/peds.2004-1847)

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ELECTRONIC ARTICLE

The Rate of Serious Bacterial Infections Among HIV-Infected Children With Immune Reconstitution Who Have Discontinued Opportunistic Infection Prophylaxis

Sharon Nachman, MD^*, Philimon Gona, PhD, Wayne Dankner, MD, Adrianna Weinberg, MD^||, Ram Yogev, MD^¶, Anne Gershon, MD^#, Mobeen Rathore, MD^**, Jennifer S. Read, MD, Sharon Huang, MS, Carol Elgie, BS, Kim Hudgens, BS^||||, Walter Hughes, MD^¶¶

^* Stony Brook University, State University of New York, Stony Brook, New York
Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts
Duke University Medical Center, Durham, North Carolina
^|| University of Colorado Health Sciences Center, Denver, Colorado
^¶ Northwestern University, Chicago, Illinois
^# Columbia Presbyterian Medical Center, New York, New York
^** University of Florida Health Science Center, Jacksonville, FL
National Institute of Child Health and Human Development, Bethesda, Maryland
Frontier Science and Technology Research Foundation, Amherst, New York
^|||| Social and Scientific Systems, Silver Spring, Maryland
^¶¶ St Jude Children's Research Hospital, Memphis, Tennessee

Objective. Receipt of highly active antiretroviral therapy is associated with a decrease in the incidence of opportunistic infections (OIs) among HIV-infected adults. The goal of Pediatric AIDS Clinical Trials Group protocol 1008 was to evaluate prospectively the incidence of serious bacterial infections (SBIs) and other OIs after discontinuation of OI and/or Pneumocystis jiroveci pneumonia (PCP) prophylaxis among HIV-infected pediatric subjects who experienced immune reconstitution while receiving stable antiretroviral therapy.

Methods. HIV-infected children and adolescents, 2 to 21 years of age, who had received OI and/or PCP prophylaxis for 6 months were enrolled if they had sustained responses (>16 weeks before study entry) to antiretroviral therapy, with CD4⁺ cell percentages of 20% for patients >6 years of age or 25% for patients 2 to 6 years of age. Prophylaxis was discontinued at entry. To identify whether any correlation existed between functional immune reconstitution and protection from OIs, subjects were immunized with the hepatitis A virus vaccine. The association between the humoral immune response and the likelihood of developing an OI was evaluated.

Results. A total of 235 HIV-infected subjects from 43 participating sites had a median follow-up period of 132 weeks, yielding 547 person-years of observation. Twenty SBIs were observed among 19 subjects, resulting in an incidence rate of 3.66 SBIs per 100 person-years (95% confidence interval: 2.24–5.66 SBIs per 100 person-years). Sixteen of the events were presumed bacterial pneumonia, with 4 proven SBIs. One participant experienced 2 separate pneumonia episodes, of presumed bacterial cause. Ten subjects who developed SBIs had baseline CD4⁺ cell counts of 750 cells per mm³, and 15 had CD4⁺ cell percentages of 25% at the time of their SBIs. Two subjects died as a result of non–SBI-related causes. There were no statistically significant differences in changes over time in CD4⁺ cell counts or CD4⁺ cell percentages between subjects who experienced primary end points and those who did not. There was no evidence that baseline protease inhibitor use, gender, race/ethnicity, age, or CD4⁺ cell count or percentage affected the time to development of a SBI.

Conclusions. OI or PCP prophylaxis can be withdrawn safely for HIV-infected pediatric patients who experience CD4⁺ cell recovery while receiving stable antiretroviral therapy. More studies are needed to assess the association between antibody responses to neoantigens and the development of SBIs.

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Key Words: pediatric HIV • bacterial infections • immune reconstitution

Abbreviations: OI, opportunistic infection • HAART, highly active antiretroviral therapy • PCP, Pneumocystis jiroveci pneumonia • MAC, Mycobacterium avium complex • PACTG, Pediatric AIDS Clinical Trials Group • SBI, serious bacterial infection • CDC, Centers for Disease Control and Prevention • HAV, hepatitis A virus • CI, confidence interval • PI, protease inhibitor

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Accepted Nov 8, 2004.

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