This trial randomizes 4,500 HIV-1-exposed children in Uganda and assesses any non-specific effects of giving the BCG vaccine either at birth or at 14 weeks of age.

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Early versus late BCG vaccination in HIV-1 exposed infants

The Bacillus Calmette–Guérin (BCG) vaccine may have beneficial so-called non-specific effects, i.e. it may protect babies from serious infections and death, a protection beyond its ability to protect them against tuberculosis (TB).

However, most of the studies that indicate that BCG may have such non-specific effects are observational in nature and are fraught with controversy. This makes it difficult to ascertain from them whether the babies who get BCG are truly less prone to severe illness because they received the vaccine or because they had a lower risk of severe illness for other reasons. Moreover, a different set of studies indicates that giving BCG later in infancy, for example at 10 weeks of age, may enhance immune responses against the vaccine and perhaps even to non-mycobacterial antigens. This may even enhance any non-specific effects of BCG. This enhanced immunity by a deferred BCG vaccine would be particularly useful among HIV-1 exposed (HE) children who show signs of impaired immunity in early infancy and in whom the appropriate timing of BCG vaccination that maximizes protection is uncertain.

This study randomizes 4,500 HIV-1-exposed Ugandan infants to receive BCG within 24 hours of being born or at 14 weeks of age. Our main study outcomes are severe illness in the first 14 weeks of life and several immunological responses to mycobacterial and non-mycobacterial antigens. The trial is conducted in three health centers in or close to Kampala. A well-timed BCG vaccination could have important additional effects in HE infants. This study could inform the development of programmatically appropriate timing of BCG vaccination
for HE infants.


Principal Investigator:
Victoria Nankabirwa, Makerere University, Uganda, and University of Bergen, Norway

Co-Principal Investigator:
Halvor Sommerfelt, University of Bergen, and Norwegian Institute of Public Health, Norway