Published online July 17, 2006
PEDIATRICS Vol. 118 No. 2 August 2006, pp. e315-e322 (doi:10.1542/peds.2005-2616)
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ARTICLE

Persistent Humoral Immune Defect in Highly Active Antiretroviral Therapy–Treated Children With HIV-1 Infection: Loss of Specific Antibodies Against Attenuated Vaccine Strains and Natural Viral Infection

Vincent Bekker, MDa, Henriëtte Scherpbier, MDa, Dasja Pajkrt, MD, PhDa, Suzanne Jurriaans, PhDb, Hans Zaaijer, MD, PhDc and Taco W. Kuijpers, MD, PhDa

a Emma Children's Hospital
b Departments of Human Retrovirology
c Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Amsterdam, Netherlands

OBJECTIVE. In the pre–highly active antiretroviral therapy era, a loss of specific antibodies was seen. Our objective with this study was to describe the loss of specific antibodies during treatment with highly active antiretroviral therapy.

METHODS. In a prospective, single-center, cohort study of 59 children with HIV-1 infection, we investigated the long-term effect of highly active antiretroviral therapy on the titers and course of specific antibodies against measles, mumps, and rubella vaccine strains compared with wild-type varicella zoster virus, cytomegalovirus, and Epstein-Barr virus.

RESULTS. During highly active antiretroviral therapy, age-adjusted CD4+ T cells and B cells increased, whereas total immunoglobulin levels declined. Although these children were preimmunized before the start of highly active antiretroviral therapy, only 24 (43%) had antibodies against all 3 measles, mumps, and rubella. Antibodies against measles, mumps, and rubella were lost in 14 (40%), 11 (38%), and 5 (11%) children who were seropositive at baseline. We also observed loss of varicella zoster virus immunoglobulin G in 7 (21%) of 34, cytomegalovirus immunoglobulin G in 3 (7%) of 45, but none of 53 Epstein-Barr virus–seropositive children. During highly active antiretroviral therapy, primary vaccination in 3 patients and 15 revaccinations in those with negative serology demonstrated incomplete seroconversion.

CONCLUSIONS. Humoral reactivity in children with HIV-1 infection remains abnormal during highly active antiretroviral therapy. Despite immune reconstitution, antibodies against live-attenuated vaccine and wild-type natural virus strains disappear over time in up to 40% of children with HIV-1 infection.

Key Words: pediatric HIV • MMR vaccination • VZV serology • immunoglobulin • CD19

Abbreviations: HAART—highly active antiretroviral therapy • MMR—measles—mumps—and rubella • VZV—varicella zoster virus • CMV—cytomegalovirus • EBV—Epstein-Barr virus • RVP—Rijksvaccintieprogramma (state vaccination program) • pVL—plasma viral load • AU—arbitrary units • Ig—immunoglobulin • VCA—viral capsid antigen

Accepted Feb 21, 2006.