Safety and Immune Response of a Rotavirus Vaccine in HIV-infected and Uninfected Children Born to HIV-infected Mothers
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: RotaTeq vaccine (Biological); RotaTeq vaccine placebo (Biological)
Phase: Phase 2
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Official(s) and/or principal investigator(s):
Myron J. Levin, MD, Study Chair, Affiliation: University of Colorado at Denver Health Sciences Center
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. 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 is to evaluate the safety and immunogenicity
of the Rotavirus vaccine candidate, RotaTeq, in HIV-infected and uninfected children born to
Official title: Safety and Immunogenicity of a Live, Attenuated Rotavirus (RotaTeq™) in HIV-1 Infected and Uninfected Children Born to HIV-1-Infected Mothers
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Safety of any dose of RotaTeq given to HIV-1-infected children born to HIV-1-infected mothers
Immunogenicity of 3-dose regimen of RotaTeq in HIV-1-infected and uninfected children born to HIV-1-infected mothers
Fecal shedding of RotaTeq strains after each dose
Relationship between anti-rotavirus serologic immune responses to CD4 count and/or CD4%, plasma RNA or DNA, and antiretroviral therapy after a 3-dose regimen of RotaTeq given to HIV-1-infected children born to HIV-1-infected mothers
Incidence of HIV infection
Relationship between virus shedding and rotavirus-specific SNA antibodies, copro-antibodies, and CMI against rotavirus vaccine serotypes in recipients of the rotavirus vaccine
IgA and IgG copro-antibodies and CMI responses against rotavirus serotypes contained in the vaccine in HIV-1-infected versus uninfected infants born to HIV-1-infected mothers
CD4% in HIV-1-infected recipients of rotavirus vaccine or placebo
Changes in microbial translocation in response to vaccination with RotaTeq relative to placebo in HIV-1-infected and uninfected participants
Relationship of mucosal and cell-mediated immune responses to CD4 counts and/or CD4%, plasma HIV RNA or DNA, and ART after 3-dose regimen of RotaTeq given to HIV-1-infected children
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. The primary purpose of this study is to
evaluate the safety and immunogenicity of the Rotavirus vaccine candidate, RotaTeq, in
HIV-infected and uninfected children born to HIV-infected mothers.
This study will last up to 18 weeks. Participants will be placed in either Group 1 or 2.
Participants in Group 1 will be HIV-uninfected. Participants in Arm 1A will receive 3 doses
of the study vaccine over a 12-week period. Participants in Arm 1B will receive 3 doses of
study vaccine placebo over a 12-week period.
Participants in Group 2 will be HIV-infected. Participants in Arm 2A will have CD4
percentages of at least 20% and receive 3 doses of the study vaccine over a 12-week period.
Participants in Arm 2B will have CD4 percentages 15 up to 20% and receive 3 doses of study
vaccine placebo over a 12-week period. Participants in Arm 2C will have CD4 percentages
between 15 - 24% and receive 3 doses of the study vaccine over a 12-week period.
Participants in Arm 2D will have CD4 percentages between 15 - 24% and receive 3 doses of
study vaccine placebo over a 12-week period. Participants in Arm 2E will have CD4
percentages less than 15% and receive 3 doses of the study vaccine over a 12-week period.
Participants in Arm 2F will have CD4 percentages less than 15% and receive 3 doses of study
vaccine placebo over a 12-week period.
There will be 16 study visits for each participant. They will occur at screening and Days 0,
7, 14, 21, 42, 49, 56, 63, 70, 91, 98, 105, 112, 119, and 140. Study vaccinations will occur
on Days 0, 49, and 98. Stool samples will be collected at most visits. Blood collection will
occur at select visits.
For any missed visits, study staff will contact participants' caregivers and conduct a study
visit at the participant's home, if possible.
If a national recommendation for rotavirus vaccine is implemented at a study site,
participants who are receiving the placebo vaccine will be discontinued from the study and
will receive the rotavirus vaccine, per site procedures.
Minimum age: N/A.
Maximum age: 14 Weeks.
Inclusion Criteria for All Steps:
- Participant was born to an HIV-1-infected mother whose HIV-1 diagnosis was determined
by two different tests performed on the same or separate maternal samples obtained
before or during pregnancy or during the post-partum period. Acceptable tests are
antibodies in serum or saliva, HIV RNA or DNA, or antigen in the blood.
- Presence or absence of HIV RNA or DNA in the blood of the infant
- CD4% is documented at screening
- Parent or legal guardian agrees to give written informed consent and is willing to
comply with study requirements
- Parents/guardians of each participant must state their willingness to have the child
follow the country-specific childhood Expanded Programme on Immunization ("EPI")
schedule for concomitant childhood vaccines recommended during the study period
Inclusion Criteria for Steps 2 and 3:
- Successful administration of first vaccine (for Step 2) and second vaccine (for Step
Exclusion Criteria for All Steps:
- Concurrent participation in any study of an investigational drug or vaccine, except
for studies for prevention of perinatal HIV-1 transmission
- Known allergy to any component of the study vaccine
- Active gastrointestinal illness or fever. Fever is defined as greater than or equal
to 38. 5Âº C in accordance with WHO guidelines for administration of childhood
- Cannot be enrolled from any site at which rotavirus vaccine is available and is being
- Any condition, including intussusception, which would, in the opinion of the site
investigator, place the participant at an unacceptable risk of injury or render them
unable to meet the requirements of the study
- Any other condition (including known history of severe combined immunodeficiency
disease [SCID]), situation, or clinically significant finding (other than HIV
infection) that, in the investigator's opinion, would interfere with study
participation, or interpretation
Exclusion Criteria for Steps 2 and 3:
- Any Grade 4 adverse events believed to be possibly/probably related to vaccine will
disqualify subjects from receiving additional doses. Grade 3 adverse events believed
to be possibly/probably related to vaccine must be demonstrated to have improved to
less than Grade 2 prior to receiving the next scheduled dose.
Locations and Contacts
Gaborone Prevention/Treatment Trials CRS, Gaborone, Botswana; Recruiting
Tebogo Kakhu, Phone: 267-393-0335, Email: email@example.com
Anthony Ogwu, MD, Principal Investigator
Molepolole Prevention/Treatment Trials CRS, Molepolole, Botswana; Recruiting
Evans Moko, Phone: 267-592-1013, Email: firstname.lastname@example.org
Aida Asmelash, MD, MPH, Principal Investigator
Committee on Infectious Diseases. Prevention of Rotavirus Disease: Updated Guidelines for Use of Rotavirus Vaccine. Pediatrics. 2009 Mar 30; [Epub ahead of print]
Kiulia NM, Nyaundi JK, Peenze I, Nyachieo A, Musoke RN, Steele AD, Mwenda JM. Rotavirus Infections among HIV-Infected Children in Nairobi, Kenya. J Trop Pediatr. 2009 Mar 18; [Epub ahead of print]
Parashar UD, Glass RI. Rotavirus vaccines--early success, remaining questions. N Engl J Med. 2009 Mar 12;360(11):1063-5. No abstract available.
Starting date: December 2009
Last updated: September 8, 2010