RV5 Levin 2017‐AF

Methods	RCT Length of follow‐up: 6 weeks after last dose Adverse event data collection methods: Active: At each visit, data were recorded on adverse events observed by the caretaker and investigator, including signs/symptoms ≥ grade 1 and new clinically significant diagnoses
Participants	Number: 202 enrolled; 202 evaluable Age range: infants 2 to < 15 weeks Inclusion criteria: Participant was born to an HIV‐infected mother; presence or absence of HIV RNA or DNA in the blood of the infant; CD4% documented at screening Exclusion criteria: concurrent participation in any study of an investigational drug or vaccine, except for studies for prevention of perinatal HIV transmission; gastrointestinal illness or fever; any condition, which would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol
Interventions	1. RV5, 2 mL solution of live reassortant rotaviruses, containing G1, G2, G3, G4 and P1A which contains a minimum of 2.0 2.8 x 106 infectious units (IU) per individual reassortant dose, depending on the serotype, and not greater than 116 x 106 IUs per aggregate dose in 62 HIV‐uninfected but exposed and 37 HIV‐infected participants 2. Placebo in 64 HIV‐uninfected but exposed and 39 HIV‐infected participants Schedule: 3 doses of RV5 or placebo at intervals of 4 ‐ 10 weeks with the third dose administered by 32 weeks of age
Outcomes	Clinical outcome measures (safety and efficacy) 1. All‐cause deaths 2. All‐cause serious adverse events 3. Hospitalization 4. Reactiogenicity: fever, diarrhoea, vomiting Outcomes to measure immunogenicity 4. Rotavirus vaccine shedding (after 3rd dose) 5. Seroconversion
Immunization status	Enrolment was closed in participating countries when RV1 was added to national vaccine schedules
Location	Botswana (2 sites), United Republic of Tanzania (1 site) , Zambia (1 site) and Zimbabwe (2 sites) WHO mortality stratum E
Notes	Date: December 2009 ‐ January 2014 Source of funding: Merck & Co., Inc. and the International Maternal, Pediatric, and Adolescent AIDS Clinical Trial Network (IMPAACT) through the National Institute of Health Study rationale: evaluate the safety and immunogenicity of the Rotavirus vaccine RotaTeq, in HIV infected and uninfected children born to HIV infected mothers
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study reported to be randomized, but no details provided on the randomization process
Allocation concealment (selection bias)	Unclear risk	No details provided
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Placebo‐controlled but no details provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low attrition, reasons provided
Selective reporting (reporting bias)	Low risk	All relevant outcomes reported
Other bias	Unclear risk	Nine infants were unblinded after their first or second dose when rotavirus vaccine became available at their site. The 4 infants found to be on RV5 continued to receive their remaining study doses. Of the 5 infants on placebo, 2 were given the 2 recommended doses of Rotarix, but 3 were too old to receive Rotarix