Pediatrics (Division of Infectious Diseases)
The Saban Research Institute
Childrens Hospital Los Angeles
Research OverviewOur laboratory has a broad-based program to investigate the transmission of HIV from mother to child and the pathogenesis of HIV in children. Last year according to the World Health Organization, 2,000 children a day became infected with HIV. Most of these children live in sub-Saharan Africa where most children are becoming infected through breast milk. Alternatives to breast-feeding in these countries are unaffordable, unsafe, and culturally unacceptable. We are involved in a large clinical trial in Africa and are using specimens collected from this well-characterized cohort to elucidate virologic and immunologic factors modulating transmission risk. Chronic HIV infection is associated with a complex, heterogeneous population of HIV variants. In contrast, a newly infected individual is usually infected with a single or a few variants. Although this transmission �bottleneck� was recognized over a decade ago, the biologic basis for this phenomenon has yet to be elucidated. Is this selection the result of an inefficient stochastic transmission event, or are these viruses selected for because of their replicative advantage in the transmitting compartment (genital secretions, breast milk, blood) and/or within the new host? We are characterizing the genotypic and functional characteristics of HIV strains transmitted via various routes. Since these early variants are the targets of preventative efforts, understanding their distinguishing features is central to vaccine development. We are also performing comprehensive virologic studies the effects of inflammation HIV evolution and transmissibility.
We have already established that breast milk is a distinct immunologic compartment. We are currently using state-of-the-art techniques to compare the cellular and humoral responses in blood and mucosal compartments and to determine their influence on transmission. These studies will help elucidate key to designing sustainable interventions to prevent mother-to-child transmission of HIV.