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Factors Associated with Robust Antibody Responses to the Hepatitis A Virus Vaccine in HIV-infected Children: International Maternal Pediatric Adolescent AIDS Clinical Trials, P1008
Adriana Weinberg*1, S Huang2, T Fenton2, J Patterson-Bartlett1, P Gona3, J Read4, W Dankner5, S Nachman6, and IMPAACT P1008 Team
1Univ of Colorado Denver Sch of Med, US; 2Statistical and Data Analysis Ctr, Harvard Sch of Publ Hlth, Boston, MA, US; 3Boston Univ, MA, US; 4Natl Inst of Child Hlth and Human Devt, NIH, Bethesda, MD, US; 5Duke Univ, Durham, NC, US; and 6State Univ of New York Hlth Sci Ctr at Stony Brook, US
Background: HIV-infected individuals typically mount poor
antibody responses to vaccines. We have previously shown that 47% of
HIV-infected children developed low antibody titers after primary hepatitis A
virus (HAV) immunization. The antibody responses to HAV are T cell-dependent,
suggesting that T cell impairment may contribute to low antibody responses.
Furthermore, HAV-specific T cells may also protect against HAV infection. Here,
we identified immunologic and virologic factors associated with the antibody
and T cell responses to the HAV vaccine in HIV-infected children receiving HAART.
Methods: In a 2-dose HAV immunization regimen, 152
HAV-naïve HIV-infected children on HAART with CD4 percentage of ≥20% had
anti-HAV antibodies and CD4, CD8, and CD19 percentages measured at weeks 0
(before) and 32 (4 weeks after completion). Subgroups of children also had
measurements of plasma HIV RNA concentration (viral load), B and T cell
subpopulations, and lymphocyte proliferation assays to HAV, Candida albicans,
tetanus, and phytohemagglutinin.
Results: Anti-HAV antibody titers at week 32 were
positively associated with baseline CD4 percentage (p = 0.04, n = 151)
and CD19 percentage (p = 0.01, n = 148), and with week 32 HAV lymphocyte
proliferation assay (p = 0.02, n = 54); negatively associated with
baseline viral load (p = 0.01, n = 99) and CD8 percentage (p = 0.04,
n = 151); and did not vary with baseline or week 32 memory or activated B or T cell
subpopulations, with non-HAV lymphocyte proliferation assays, or with week 32
CD4, CD8, or CD19 percentage. Compared with HAV lymphocyte proliferation assay-negative
subjects, those with positive HAV lymphocyte proliferation assays at week 32
had higher CD19+CD21+CD27+ percentage memory B
cells at week 32 (p = 0.02, n = 56), indicating an important
bidirectional cooperation between B and T cells in the generation of anti-HAV
responses. There were no other significant associations for HAV lymphocyte
proliferation assays.
Conclusions: Control of HIV replication and conserved or
reconstituted numbers and function of B and CD4+ T lymphocytes are
critical factors for a robust immune response to HAV primary immunization in
HIV-infected children on HAART.
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