title: Safety, Reactogenicity, and Immunogenicity of Human Rotavirus Vaccine RIX4414 in Human Immunodeficiency Virus-positive Infants in South Africa.
abstract: BACKGROUND
  rotavirus and human immunodeficiency virus (HIV) infections are a cause of great public health concern in developing countries. The current study evaluated the safety, reactogenicity, and immunogenicity of RIX4414 vaccine in asymptomatic or mildly symptomatic (clinical stages I and II according to WHO classification) HIV-infected South African infants.
  
  
  METHODS
  a total of 100 HIV-positive infants aged 6 to 10 weeks enrolled in this double-blind, 1:1 randomized, placebo-controlled study were allocated into 2 groups to receive 3 doses of RIX4414 vaccine/placebo according to a 0-, 1-, and 2-month schedule. Routine vaccines were concomitantly administered. Solicited and unsolicited symptoms were recorded for 15 and 31 days after each dose, respectively. Serious adverse events were recorded throughout the study period. Serum antirotavirus IgA concentrations (enzyme-linked immunosorbent assay, cut-off ≥ 20 U/mL) and the immunodeficiency status were determined at screening and 2 months post-Dose 3. Stool samples were analyzed for rotavirus using enzyme-linked immunosorbent assay at predetermined points and during diarrhea episodes.
  
  
  RESULTS
  all symptoms (solicited and unsolicited) occurred at a similar frequency in both groups. Six fatal serious adverse events in RIX4414 and 9 in placebo groups were reported. At 2 months post-Dose 3, the seroconversion rates were 57.1% (95% CI: 34-78.2) in RIX4414 and 18.2% (95% CI: 5.2-40.3) in the placebo group. The mean absolute CD4 cell count, CD4 percentage, and HIV-1 viral load were comparable in both groups at screening and 2 months post-Dose 3. Rotavirus shedding peaked at Day 7 after Dose 1 of RIX4414 with prolonged shedding was observed in 1 infant only.
  
  
  CONCLUSIONS
  : Three doses of RIX4414 vaccine was tolerated well by the South African HIV-positive infants. A satisfactory immune response was mounted without aggravating their immunologic or HIV condition.
authors.affiliation: Initiative for Vaccine Research, Department of Immunization, Vaccines and Biologicals, WHO, Geneva, Switzerland. dsteele@path.org
authors.forename: Andrew Duncan
authors.initials: AD
authors.lastname: Steele
authors.forename: Shabir Ahmed
authors.initials: SA
authors.lastname: Madhi
authors.forename: Cheryl Emily
authors.initials: CE
authors.lastname: Louw
authors.forename: Pieter
authors.initials: P
authors.lastname: Bos
authors.forename: John M
authors.initials: JM
authors.lastname: Tumbo
authors.forename: Corne M
authors.initials: CM
authors.lastname: Werner
authors.forename: Ceyhun
authors.initials: C
authors.lastname: Bicer
authors.forename: Beatrice
authors.initials: B
authors.lastname: De Vos
authors.forename: Andree
authors.initials: A
authors.lastname: Delem
authors.forename: Htay Htay
authors.initials: HH
authors.lastname: Han
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D003967:Diarrhea / Q000821:virology; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000821:virology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007070:Immunoglobulin A / Q000097:blood; D007223:Infant; D010919:Placebos / Q000008:administration & dosage; D012401:Rotavirus / Q000302:isolation & purification; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D013019:South Africa; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D010919:Placebos; C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated