HIV Exposure, HIV Infection
Conditions
Keywords
Vaccine immunogenicity, Immune activation
Brief summary
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.
Interventions
BIOLOGICALBCG
Sponsors
Seattle Children's Hospital
University of Stellenbosch
University of Cape Town
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Hours
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| T Cell Activation | at 6 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vaccine Immunogenicity | 6 weeks after BCG vaccination | Percent of CD4+ T cells expressing Ki67 after stimulation in vitro with BCG. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Delayed BCG BCG delayed to 8 weeks of age
BCG | 71 |
| Early BCG BCG at birth; standard of care
BCG | 78 |
| Total | 149 |
Baseline characteristics
| Characteristic | Delayed BCG | Early BCG | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 71 Participants | 78 Participants | 149 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 39 weeks | 40 weeks | 39.5 weeks |
| Birth weight | 3.15 kg | 3.12 kg | 3.13 kg |
| Breastfed no | 62 participants | 64 participants | 126 participants |
| Breastfed yes | 8 participants | 12 participants | 20 participants |
| Maternal CD4 T cell count | 358 cells/mm^3 | 366 cells/mm^3 | 362 cells/mm^3 |
| Region of Enrollment South Africa | 70 count of participants | 76 count of participants | 146 count of participants |
| Sex: Female, Male Female | 41 Participants | 46 Participants | 87 Participants |
| Sex: Female, Male Male | 30 Participants | 32 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 71 | 30 / 78 |
| serious Total, serious adverse events | 2 / 71 | 7 / 78 |
Outcome results
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.
Time frame: at 6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Delayed BCG | T Cell Activation | 1.8 percentage of CD4+ T cells |
| Early BCG | T Cell Activation | 1.3 percentage of CD4+ T cells |
Secondary
Vaccine Immunogenicity
Percent of CD4+ T cells expressing Ki67 after stimulation in vitro with BCG.
Time frame: 6 weeks after BCG vaccination
Population: Analysis population n is smaller than enrollment numbers as we calculated that that only 28 were needing in each arm to detect a difference.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Delayed BCG | Vaccine Immunogenicity | 22.4 percentage of Ki67% CD4+ T cells |
| Early BCG | Vaccine Immunogenicity | 20.5 percentage of Ki67% CD4+ T cells |