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.
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.
Bekker
Vincent
V
Emma Children's Hospital, Academic Medical Center, Room G8-205, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.
Scherpbier
Henriëtte
H
Pajkrt
Dasja
D
Jurriaans
Suzanne
S
Zaaijer
Hans
H
Kuijpers
Taco W
TW
D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D014645:Herpesvirus 3, Human / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D008211:Lymphocyte Cooperation; D018655:Lymphocyte Count; D008297:Male; D008459:Measles virus / Q000276:immunology; D022542:Measles-Mumps-Rubella Vaccine / Q000276:immunology*; D009109:Mumps virus / Q000276:immunology; D011446:Prospective Studies; D012412:Rubella virus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology*; D019562:Viral Load; D014777:Virus Diseases / Q000276:immunology*
D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D022542:Measles-Mumps-Rubella Vaccine; D014613:Vaccines, Attenuated