Safety and Immune Response of a Rotavirus Vaccine in HIV-infected and Uninfected Children Born to HIV-infected Mothers

• Percentage of Participants Developing New Grade >=3 Adverse Events [ Time Frame: From study entry until at least 42 days after third vaccination ] [ Designated as safety issue: Yes ]
  Percentage of participants developing new grade >=3 adverse events (abnormal laboratory values (hematology and chemistry), signs, symptoms and diagnoses) not present at the time of the first vaccination. Adverse events were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (Version 1.0, December 2004, Clarification August 2009).
  
  
• Percentage of Participants Classified as Responders as Measured by Serum Anti-rotavirus IgA ELISA (IgA) and Serum Neutralizing Antibodies (SNA) G1, G2, G3, G4 and P1. [ Time Frame: Prior to first vaccination and at least 14 days after third vaccination ] [ Designated as safety issue: No ]
  Percentage of participants who experienced >=3-fold increases from prior to the first vaccination to at least 14 days after the third vaccination in Iga, SNA G1, SNA G2, SNA G3, SNA G4 and SNA P1.
  
  

• Number of Participants With Fecal Shedding of RotaTeq Strains After Each Vaccination [ Time Frame: At entry, days 7, 14, 21 and 42 days after first dose, and at days 7 and 21 after the second and third doses ] [ Designated as safety issue: No ]
  Number of participants with at least one positive enzyme immuno assay (EIA) rotavirus antigen test, positive fluorescent focal assay, and specific for rotavirus gene 6 which codes for the VP6 protein after each vaccination.
  
  
• Percentage of HIV-1 Infected Participants With HIV-1 RNA <= 400 Copies/ml [ Time Frame: 42 days after third vaccination or last study visit with an HIV-1 RNA measurement ] [ Designated as safety issue: No ]
  Percentage of HIV-1 infected participants with HIV-1 RNA <= 400 copies/ml at last study visit
  
  
• Change in CD4 Percent From Entry to Last Study Visit in HIV-1 Infected Participants [ Time Frame: At entry and 42 days after third vaccination or last study visit with CD4 measurement ] [ Designated as safety issue: No ]
  Change calculated as value at last study visit minus value closest to and before randomization date
  
  
• Change in CD4 Count From Entry to Last Study Visit in HIV-1 Infected Participants [ Time Frame: At entry and 42 days after third vaccination or last study visit with CD4 measurement ] [ Designated as safety issue: No ]
  Change calculated as value at last study visit minus value closest to and before randomization date
  
  
• Number of Participants Classified at Screening or Entry as HIV-1 Uninfected, and Acquiring HIV-1 Infection on Study [ Time Frame: From study entry until at least 42 days after third vaccination ] [ Designated as safety issue: Yes ]
  HIV tests were done at screening, entry and the last study visit after the third vaccination. Any participants classified as HIV-1 uninfected at screening or entry but HIV-1 infected at their last study visit would be classified as acquiring HIV-1 infection during the study
  
  

International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1072 was an international Phase II randomized double-blind study to assess the safety and immunogenicity of a live, attenuated rotavirus vaccine (RotaTeq) in HIV-1 infected (n=160) and uninfected (n=160) children born to HIV-1 infected mothers. Infants between 2 and <15 weeks of age at screening were assigned to one of four strata, based on HIV-1 status and in the HIV-1 infected, by Cluster of Differentiation percentage (CD4%) [≥ 20% (n=80), 15% ≤ CD4% < 20% (n=60) and < 15% (n=20)]. Screening had to be completed such that the first dose of study vaccine was administered when the participant was 4 to < 15 weeks of age. Within each stratum infants were randomized to receive either active RotaTeq vaccine (three doses of 2.0 mL each at intervals of 4 to 10 weeks with the third dose administered by 32 weeks of age) or placebo on the same schedule.

Participants were followed until six weeks after the last dose of vaccine, with visits at 7, 14, 21 and 42 days after each dose. The day 42 visit after the first two study doses was only required if the next study vaccination was done more than 42 days after the previous dose. 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. No hematology or chemistry testing was required by the protocol, but sites could record laboratory results in the database if the results were pertinent. Stool samples for fecal shedding were collected at entry, days 7, 14, 21 and 42 after the first vaccination, 7 and 21 days after the second and third vaccinations, and at any unplanned visits for gastroenteritis. Serum for immunogenicity testing was collected at entry and 14 days (or 42 days if not collected at 14 days) after the third vaccination.

In January 2012, rotavirus vaccine (Rotarix) became available as standard of care at the Lusaka study site in Zambia, so enrollment ceased at that site. Infants already enrolled and within the age range where they could receive the Rotarix series were unblinded. Those on placebo were given Rotarix. Those in the active vaccine arm continued receiving the study vaccine. All infants continued to attend study visits. A similar procedure was followed after July 2012, when Rotarix became available as standard of care in Botswana.

During 2013, Zimbabwe was the only site enrolling participants, most of whom were HIV-1 uninfected. The team decided to close the study to enrollment prematurely at the end of September 2013 with a total of 126 HIV-1 uninfected (79% of the target of 160) and 76 HIV-1 infected (48% of the target: 81% of those with CD4% ≥ 20% and 14% of those with CD4% < 20%). Because of the low enrollment of HIV-1 infected infants with lower CD4%, results in the HIV-1 infected stratum were reported combined across CD4% strata.

Baseline characteristics are presented 'as-randomized'. Safety data are presented 'as-randomized' and include all follow-up on study up to 42 days after the third vaccination. Immunogenicity results are presented for the 'per-protocol' population which includes participants who received the 'as-randomized' vaccine and completed the three vaccinations within the required windows (first vaccination between 4 and < 15 weeks of age, subsequent vaccinations at least 28 days after previous vaccination, and third dose by 32 weeks of age).