Safety and immunogenicity of a live attenuated pentavalent rotavirus vaccine in HIV-exposed infants with or without HIV infection in Africa.
Although many HIV-infected (HIV+) and HIV-exposed but uninfected (HEU) infants have received live rotavirus vaccines since the WHO recommended universal administration of these vaccines to infants, there has been limited prospective information on their safety and immunogenicity in either group of infants.



We performed a randomized, double-blinded, placebo-controlled trial of the safety and immunogenicity of oral pentavalent rotavirus vaccine (RV5) administered to HIV+ and HEU infants in four African countries. Ninety-three percent of HIV+ infants were receiving antiretroviral therapy prior to vaccination. Participants were followed for safety. Immune responses were measured 14 days after three doses of RV5, including serum antirotavirus neutralizing and IgA antibodies, IgA antibody in stool, and antirotavirus memory B and T-cell FluoroSpot. Shedding of RV5 in stool was monitored.



A total of 76 HIV+ and 126 HEU infants were enrolled from 2009 to 2013. No significant differences were found in adverse event rates, including grade 3 events, between RV5 and placebo recipients, for either HIV+ or HEU infants. The proportion of antirotavirus IgA responders (at least three-fold increase from baseline) after RV5 administration was 81% in both HIV+ and HEU infants, which was approximately 2.5-fold higher than in placebo recipients (P < 0.001). Neutralizing antibody responses to three of five serotypes were significantly higher after RV5 regardless of HIV status, and those of HIV+ infants were equal or greater than responses of HEU infants to all five serotypes. Only one HIV+ RV5 recipient had RV5 isolated from stool.



RV5 was immunogenic in both HIV+ and HEU infants and no safety signals were observed.
aSection of Pediatric Infectious Diseases, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado bCenter for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts cMerck & Co, Inc., Kenilworth, New Jersey, USA dSection of Health Promotion, Department of Health and Environment, Municipality of Munich, Munich, Germany ePfizer Inc., Collegeville, Pennsylvania fDivision of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA gDepartment of Paediatrics and Child Health, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe hFormerly Harvard AIDS Institute, Gaborone, Botswana; currently Trinity Medical Centre, Port Adelaide, South Australia, Australia iDepartment of Pediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia jFormerly Maternal Adolescent and Pediatric Research Branch, NIAID, NIH, Rockville; currently Office of AIDS Research, NIH kMaternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland lDepartment of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York mSection of Pediatric Infectious Diseases, Departments of Pediatrics, Medicine, and Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Myron J
MJ
Levin
Jane C
JC
Lindsey
Susan S
SS
Kaplan
Werner
W
Schimana
Jody
J
Lawrence
Monica M
MM
McNeal
Mutsa
M
Bwakura-Dangarembizi
Anthony
A
Ogwu
Evans M
EM
Mpabalwani
Paul
P
Sato
George
G
Siberry
Margaret
M
Nelson
Darcy
D
Hille
Geoffrey A
GA
Weinberg
Adriana
A
Weinberg
D000349:Africa; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005243:Feces / Q000737:chemistry / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007223:Infant; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D011446:Prospective Studies; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D017201:Virus Shedding
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D010919:Placebos; C492535:RotaTeq; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated
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