Paediatric HIV infection: correlates of protective immunity and global perspectives in prevention and management

The impact of the HIV epidemic on child health globally is beginning to be appreciated. With the burden of new infections falling on young women, ther e is a skyrocketing number of AIDS orphans, and a rapidly increasing number of children infected via mother-to-child-transmission (MTCT). An estimated 600,000 new paediatric infections occur each year, of which some 1500/day (>90%) occur in sub-Saharan Africa. But whereas children account for only 4 % of those currently living with HIV infection, 20% of AIDS deaths have bee n in children. This reflects the rapid progression to disease in paediatric HIV infection. Whereas a dramatic reduction in viraemia follows acute adul t infection, corresponding to the appearance of a vigorous anti-HIV cytotox ic T lymphocyte response, virtually no impact of the immune response is obs erved in acute paediatric infection following MTC-T. Two specific challenge s for the paediatric immune response are: (i) infection occurs before the i mmune system itself is fully developed; and (ii) the viruses transmitted by MTCT have already evaded an immune system sharing close genetic relatednes s to that of the child. Accumulating evidence! indicates that the immune sy stem is potentially capable of effective control of HIV infection, and that events occurring in acute infection critically determine the ultimate outc ome. Technological advances that have transformed the study of T-cell immun ity now enable the developing immune system in childhood to be better under stood. Via novel immunotherapeutic approaches described, it may be possible to modulate the infant's immune response to reach effective and durable su ppression of HIV, as can be achieved by the rare long-term non-progressors of HIV infection. The feasibility of adopting these approaches globally are as yet untested. Finally, the striking disparity between the burden of pae diatric HIV infection and access to the necessary infrastructure and therap eutic options required for its optimal management is addressed in a compari son between three sites of paediatric HIV care: Durban, South Africa; Londo n, UK; and Boston, USA.