Effect of HIV-1 exposure and antiretroviral treatment strategies in HIV-infected children on immunogenicity of vaccines during infancy.
BACKGROUND
We studied the effect of maternal HIV-exposure and timing of antiretroviral treatment (ART) in HIV-infected infants on antibody responses to combined diphtheria-toxoid-tetanus-toxoid-whole cell pertussis and Haemophilus influenzae type b conjugate vaccine (HibCV) and monovalent hepatitis B vaccine (HBV).


METHODS
HIV-uninfected infants born to HIV-infected (HEU) or HIV-uninfected (HUU) mothers were enrolled in parallel with HIV-infected children with CD4⁺ ≥25%, who were randomized to initiate ART immediately upon confirmation of HIV-infection (ART-Immed) or when clinically and/or immunologically indicated (ART-Def). Infants received three doses of diphtheria-toxoid-tetanus-toxoid -wP-HibC/HBV at 7.3, 11.4 and 15.4 weeks of age. Antibody to diphtheria-toxoid, tetanus-toxoid, pertussis toxin, filamentous hemagglutinin (FHA) and hepatitis B surface antigen (HBsAg) were measured by Luminex multiplex-immunoassay and polyribosyl-ribitol phosphate (PRP) antibodies by standard ELISA and bactericidal assay.


RESULTS
Prevaccination antibody geometric mean concentrations (GMCs) were higher in HUU than HEU infants for tetanus-toxoid, but lower for HBsAg, diphtheria-toxoid and FHA. Postvaccination GMCs and proportion with seroprotective antibody levels or sero-conversion rates were similar between HUU and HEU infants for all vaccines. Postvaccination GMCs were higher in HUU for tetanus-toxoid, diphtheria-toxoid, HBsAg and FHA than ART-Immed infants; and for tetanus-toxoid, HBsAg and pertussis-toxoid than ART-Def infants. Nevertheless, there was no difference in proportion of HUU and HIV-infected infants who developed sero-protective vaccine-specific antibody levels postvaccination. The timing of ART initiation generally did not affect immune responses to vaccines between HIV-infected groups.


CONCLUSIONS
Vaccination with DTwP-HibCV/HBV of HEU and HIV-infected infants initiated on early-ART confers similar immunity compared with HUU children.
aDepartment of Science and Technology/National Research Foundation: Vaccine Preventable Diseases; Johannesburg bMedical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty Health Sciences; University of the Witwatersrand, Faculty of Health Sciences, Johannesburg; cPerinatal HIV Research Unit, University of the Witwatersrand, Faculty of Health Sciences dStellenbosch University, Children's Infectious Diseases Clinical Research Unit, Tygerberg eDivision of National Health Laboratory Service, National Institute for Communicable Diseases, Centre for Vaccines and Immunology, Sandringham, South Africa.
Omphile E
OE
Simani
Alane
A
Izu
Avy
A
Violari
Mark F
MF
Cotton
Nadia
N
van Niekerk
Peter V
PV
Adrian
Shabir A
SA
Madhi
D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000907:Antibodies, Bacterial / Q000097:blood*; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000097:blood*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007118:Immunoassay; D007223:Infant; D008297:Male
D044966:Anti-Retroviral Agents; D000907:Antibodies, Bacterial; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; C080881:diphtheria-tetanus-pertussis-haemophilus b conjugate vaccine