Safety and Immune Response of a Rotavirus Vaccine in HIV-infected and Uninfected Children Born to HIV-infected Mothers
Condition: HIV Infection; Rotavirus Infection
MeSH terms: Infections; Communicable Diseases; Rotavirus Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      Rotavirus is the leading cause of severe diarrhea in infants and young children, accounting
      for 45% of severe diarrhea disease in both developed and developing countries. Annually,
      rotavirus causes approximately 111 million episodes of gastroenteritis requiring home care,
      25 million clinic visits, 2 million hospitalizations, and approximately 440,000 deaths in
      children less than 5 years of age, of which approximately 90% of hospitalizations and 99% of
      deaths occur in developing countries. Although rotavirus infection is not more common in
      HIV-infected children, it complicates their care and interferes with their nutrition. Chances
      of death by these infections can be greater in HIV-infected children when they also suffer
      from wasting, malnutrition, and/or opportunistic infections. The primary purpose of this
      study was to evaluate the safety and immunogenicity of the Rotavirus vaccine candidate,
      RotaTeq, in HIV-infected and uninfected children born to HIV-infected mothers.
    

Detailed description: 
      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).
    

Intervention name(s): RotaTeq; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): 2 mL solution of live reassortant rotaviruses, containing G1, G2, G3, G4 and P1A which contains a minimum of 2.0 - 2.8 x 10^6 infectious units (IU) per individual reassortant dose, depending on the serotype, and not greater than 116 x 10^6 IUs per aggregate dose; 2 mL solution
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Rotavirus; Rotavirus vaccine