Early Versus Delayed BCG Vaccination of HIV-exposed Infants

Study Overview
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Brief Summary
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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.

Official Title
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Influence of BCG Immunization on Immune Responses and Disease Progression in South African HIV Exposed and Infected Infants

Conditions
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HIV Exposure, HIV Infection

Intervention / Treatment
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* Biological: BCG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy neonate Maternal HIV > 36 weeks gestation Birth weight > 2.4kg Remaining in area 4 months Exclusion Criteria: Complications during pregnancy and delivery Household TB contacts

Ages Eligible for Study
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Maximum Age: 24 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Delayed BCG<br>BCG delayed to 8 weeks of age | Biological: BCG<br> <br> |
| Other: Early BCG<br>BCG at birth; standard of care | Biological: BCG<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine Immunogenicity | Percent of CD4+ T cells expressing Ki67 after stimulation in vitro with BCG. | 6 weeks after BCG vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine immunogenicity, Immune activation