title: Safety of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), in Kenya, including among HIV-infected and HIV-exposed infants.
abstract: Two multicenter Phase III trials were conducted in five countries from March 2007 to March 2009 to evaluate the safety and efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), in Africa and Asia. In this report, we evaluate the safety of this vaccine, including among HIV-infected and HIV-exposed infants, in Kenya. 1308 Infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age. HIV counseling and testing were offered to all participants. A positive PCR result indicated HIV infection; the presence of HIV antibody in PCR-negative children indicated HIV exposure without HIV infection. All serious adverse events (SAE) within 14 days of any dose, and vaccine-related SAEs, intussusception, and deaths occurring at any time during the study, were reported ("SAE surveillance"). In addition, 297 participants were followed for 42 days after any dose for any adverse event (AE), regardless of severity ("intensive safety surveillance"). The safety evaluation was stratified by HIV status. SAEs were reported in 20/649 vaccine recipients (3.1%) and 21/643 placebo recipients (3.3%) within 14 days following vaccination (p = 0.9). The most common SAE in the vaccinated group was pneumonia (1.7%). No individual SAE was significantly more common among vaccine vs. placebo recipients. Seventy-two deaths were reported, 38 (5.9%) and 34 (5.3%) among vaccine and placebo recipients, respectively (p = 0.66). No cases of intussusception were reported. During intensive safety surveillance, 137/147 (93.2%) vaccine recipients and 147/150 (98.0%) placebo recipients experienced one or more AEs (risk ratio = 0.95; 95% CI: 0.91-1.0; p = 0.05). 88.5% of the infants were tested for HIV infection; 21/581 (3.6%) children in the vaccine group and 17/577 (2.9%) in the placebo group were HIV-infected. Among the 37 HIV-infected infants with full safety follow-up, 5/21 (23.8%) vaccine recipients and 2/16 (12.5%) placebo recipients reported an SAE (p = 0.67). In total, 12 deaths occurred among identified HIV-infected infants: 8 (38%) receiving vaccine vs. 4 (23.5%) receiving placebo (RR = 1.6, 95% CI: 0.59-4.5). Among the 21 HIV-infected infants in the vaccine group, 2 of 8 deaths were gastroenteritis-related; among the 17 HIV-infected infants in the placebo group, 3 of 4 deaths were gastroenteritis-related. There were no significant differences in serious or non-serious AEs, including vaccine-related SAEs, between the 88 HIV-exposed vaccine recipients vs. the 89 HIV-exposed placebo recipients. PRV appears to be a safe intervention against rotavirus gastroenteritis among infants in Kenya. AEs, including serious AEs, were not associated with receipt of vaccine. Further, SAEs were not significantly more common among HIV-infected or HIV-exposed participants; however, the low number of HIV-infected infants did not provide sufficient power to fully assess safety in HIV-infected vaccine recipients.
authors.affiliation: Kenya Medical Research Institute/Centers for Disease Control and Prevention Research and Public Health Collaboration, Kenya. klaserson@ke.cdc.gov
authors.forename: Kayla F
authors.initials: KF
authors.lastname: Laserson
authors.forename: Daveline
authors.initials: D
authors.lastname: Nyakundi
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Feikin
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Nyambane
authors.forename: Earnest
authors.initials: E
authors.lastname: Cook
authors.forename: Janet
authors.initials: J
authors.lastname: Oyieko
authors.forename: Joel
authors.initials: J
authors.lastname: Ojwando
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Rivers
authors.forename: Max
authors.initials: M
authors.lastname: Ciarlet
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Neuzil
authors.forename: Robert F
authors.initials: RF
authors.lastname: Breiman
mesh_terms: D000284:Administration, Oral; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D005759:Gastroenteritis / Q000453:epidemiology / Q000517:prevention & control*; D006678:HIV / Q000302:isolation & purification; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000150:complications / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007443:Intussusception / Q000139:chemically induced / Q000453:epidemiology; D007630:Kenya / Q000453:epidemiology; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D012400:Rotavirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D014611:Vaccination / Q000009:adverse effects* / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D015483:HIV Antibodies; D010919:Placebos; C492535:RotaTeq; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated