Effect of HIV exposure and timing of antiretroviral therapy initiation on immune memory responses to diphtheria, tetanus, whole cell pertussis and hepatitis B vaccines

Expert Rev Vaccines. 2019 Jan;18(1):95-104. doi: 10.1080/14760584.2019.1547195. Epub 2018 Nov 19.

Abstract

Objectives: We evaluated memory responses and antibody persistence to diphtheria-toxoid, tetanus-toxoid, whole-cell-pertussis (DTwP), and Hepatitis-B vaccines in HIV-unexposed, HIV-exposed-uninfected and HIV-infected children previously randomized to initiate time-limited ART at 6-10 weeks (ART-Immed) or when clinically/immunologically indicated (ART-Def).

Methods: All children received DTwP booster at 15-18 months. Antibodies were measured for pertussis-toxoid, filamentous haemagglutinin (FHA), diphtheria-toxoid, tetanus-toxoid, and hepatitis-B prior to booster, 1-2 weeks post-booster and at 24 months of age.

Results: Pre-booster antibody GMC were lower in HIV-infected groups than HIV-unexposed children for all epitopes. Post-booster and at 24 months of age, the ART-Def group had lower GMCs and antibody proportion ≥0.1 IU/ml for tetanus-toxoid and diphtheria-toxoid compared to HIV-unexposed children. At 24 months of age, the ART-Immed group had higher GMCs, and more likely to maintain antibody titres ≥1.0 IU/ml to tetanus-toxoid and diphtheria-toxoid compared to HIV-unexposed children. Compared to HIV-unexposed children, at 15 and 24 months of age, persistence of antibody to HBsAg of ≥10 mIU/ml was similar in the ART-Immed group but lower among the ART-Def group. Antibody kinetics indicated more robust memory responses in HIV-exposed-uninfected than HIV-unexposed children to diphtheria-toxoid and wP.

Conclusion: HIV-infected children not on ART at primary vaccination had poorer memory responses, whereas HIV-exposed-uninfected children mounted robust memory responses.

Keywords: Diphtheria-toxoid; HIV-exposed uninfected; HIV-infected; booster; hepatitis B vaccine; pertussis vaccine; tetanus-toxoid.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Antibodies / immunology
  • Child, Preschool
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage
  • Diphtheria-Tetanus-Pertussis Vaccine / immunology*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology*
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / immunology*
  • Humans
  • Immunization, Secondary / methods
  • Immunologic Memory
  • Infant
  • Male
  • Time Factors

Substances

  • Anti-HIV Agents
  • Antibodies
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Hepatitis B Vaccines