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| Name | Class |
|---|---|
| Seattle Children's Hospital | OTHER |
| University of Stellenbosch | OTHER |
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In sub-Saharan Africa (SSA), more than 300,000 babies with HIV die each year. HIV-infected children develop AIDS and die faster in SSA than those in developed countries. Bacille Calmette-Guerin (BCG) vaccine is given to infants at birth in SSA to protect them from severe forms of TB. BCG is known to cause immune cells to be active and replicate faster. The immune system of neonates also responds differently to BCG that to other vaccines and infections. We hypothesize that the routine immunization of neonates with BCG contributes to generalized immune activation in HIV-exposed infants resulting in skewed immune responses to vaccines and infections and increased rates of disease progression in those infants that become HIV-infected. However, delaying BCG until HIV testing is completed would result in operational difficulties, and may not induce the appropriate immune response. Delayed BCG would also render many HIV-exposed uninfected infants at high risk for disseminated TB. We plan to assess immune cells in infants to determine the impact of the timing of BCG vaccination on immune responses to tuberculosis (TB) and other vaccines. We will also compare the immune activation and disease progression of those infants that become HIV-infected in the BCG or control arms. Our results will provide key insights into the effect of BCG vaccination on immune responses to HIV as well as inform the optimal timing of BCG vaccination for HIV-exposed infants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Delayed BCG | Active Comparator | BCG delayed to 8 weeks of age |
|
| Early BCG | Other | BCG at birth; standard of care |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BCG | Biological |
|
| Measure | Description | Time Frame |
|---|---|---|
| T Cell Activation | Percentage of all CD4+ T cells expressing HLADR (NOT BCG-specific activation as in Tchakoute et al and as in secondary outcome). The n is smaller than the enrollment number as some participants were lost to follow-up, some were excluded due to HIV infection etc, and some samples did not have sufficient cells to analyse. | at 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Vaccine Immunogenicity | Percent of CD4+ T cells expressing Ki67 after stimulation in vitro with BCG. | 6 weeks after BCG vaccination |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Heather B Jaspan, MD, PHD | University of Cape Town | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28405623 | Derived | Gasper MA, Hesseling AC, Mohar I, Myer L, Azenkot T, Passmore JS, Hanekom W, Cotton MF, Crispe IN, Sodora DL, Jaspan HB. BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial. JCI Insight. 2017 Apr 6;2(7):e91963. doi: 10.1172/jci.insight.91963. | |
| 26259542 | Derived | Blakney AK, Tchakoute CT, Hesseling AC, Kidzeru EB, Jones CE, Passmore JA, Sodora DL, Gray CM, Jaspan HB. Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants. Vaccine. 2015 Sep 11;33(38):4782-9. doi: 10.1016/j.vaccine.2015.07.096. Epub 2015 Aug 7. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Delayed BCG | BCG delayed to 8 weeks of age BCG |
| FG001 | Early BCG | BCG at birth; standard of care BCG |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Delayed BCG | BCG delayed to 8 weeks of age BCG |
| BG001 | Early BCG | BCG at birth; standard of care BCG |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | T Cell Activation | Percentage of all CD4+ T cells expressing HLADR (NOT BCG-specific activation as in Tchakoute et al and as in secondary outcome). The n is smaller than the enrollment number as some participants were lost to follow-up, some were excluded due to HIV infection etc, and some samples did not have sufficient cells to analyse. | Posted | Median | Inter-Quartile Range | percentage of CD4+ T cells | at 6 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Delayed BCG | BCG delayed to 8 weeks of age BCG |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HIV infection | Immune system disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blocked nostrils | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Heather Jaspan | University of Cape Town and University of Washington | +2721 4066823 | hbjaspan@gmail.com |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| 25108027 | Derived | Tchakoute CT, Hesseling AC, Kidzeru EB, Gamieldien H, Passmore JA, Jones CE, Gray CM, Sodora DL, Jaspan HB. Delaying BCG vaccination until 8 weeks of age results in robust BCG-specific T-cell responses in HIV-exposed infants. J Infect Dis. 2015 Feb 1;211(3):338-46. doi: 10.1093/infdis/jiu434. Epub 2014 Aug 8. |
| BG002 |
| Total |
Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median gestational age, in weeks | Median | Inter-Quartile Range | weeks |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | count of participants |
|
| Birth weight | Median | Inter-Quartile Range | kg |
|
| Maternal CD4 T cell count | Median | Inter-Quartile Range | cells/mm^3 |
|
| Breastfed | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Vaccine Immunogenicity | Percent of CD4+ T cells expressing Ki67 after stimulation in vitro with BCG. | Analysis population n is smaller than enrollment numbers as we calculated that that only 28 were needing in each arm to detect a difference. | Posted | Median | Inter-Quartile Range | percentage of Ki67% CD4+ T cells | 6 weeks after BCG vaccination |
|
|
|
| 2 |
| 71 |
| 29 |
| 71 |
| EG001 | Early BCG | BCG at birth; standard of care BCG | 7 | 78 | 30 | 78 |
| Death | General disorders |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Fever | General disorders | Non-systematic Assessment |
|
| Rash- nonspecific | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Diaper Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
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| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |