Early Versus Delayed BCG Vaccination of HIV-exposed Infants

Phase 2

Completed

• Conditions: HIV Exposure; HIV Infection
• Interventions: Biological: BCG

• Registration Number: NCT02062580
• Lead Sponsor: University of Cape Town

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06
• Primary Completion: 2012-04
• Study First Submitted: 2014-02-12
• Study First Submitted QC: 2014-02-12
• Study First Posted: 2014-02-13
• Results First Submitted: 2016-10-25
• Status Verified: 2017-01
• Results First Submitted QC: 2017-01-25
• Last Update Submitted: 2017-01-25
• Results First Posted: 2017-03-15
• Last Update Posted: 2017-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 149

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Delayed BCG	BCG	BCG delayed to 8 weeks of age
Early BCG	BCG	BCG at birth; standard of care

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Vaccine Immunogenicity	6 weeks after BCG vaccination	Percent of CD4+ T cells expressing Ki67 after stimulation in vitro with BCG.