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

Pediatrics. 2006 Aug;118(2):e315-22. doi: 10.1542/peds.2005-2616. Epub 2006 Jul 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Antibodies, Viral / biosynthesis*
  • Antibodies, Viral / blood
  • Antiretroviral Therapy, Highly Active*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cytomegalovirus / immunology
  • Disease Susceptibility
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1*
  • Herpesvirus 3, Human / immunology
  • Herpesvirus 4, Human / immunology
  • Humans
  • Lymphocyte Cooperation
  • Lymphocyte Count
  • Male
  • Measles virus / immunology
  • Measles-Mumps-Rubella Vaccine / immunology*
  • Mumps virus / immunology
  • Prospective Studies
  • Rubella virus / immunology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • Vaccines, Attenuated / immunology*
  • Viral Load
  • Virus Diseases / immunology*

Substances

  • Anti-HIV Agents
  • Antibodies, Viral
  • Measles-Mumps-Rubella Vaccine
  • Vaccines, Attenuated