Immunological and genetic correlates of delayed HIV disease progression in children with perinatally-acquired HIV-1 infection, Harare, Zimbabwe.

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Ninety-percent of some 3 million HIV-infected children worldwide live in Sub-Saharan Africa. Although only 50% of perinatally-infected children were expected to survive beyond two years of age in the pre-antiretroviral therapy (ART) era, recent reports from the Southern Africa region describe a growing population of adolescents living with untreated vertically-acquired HIV infection. This study aims to investigate the immunological and genetic correlates associated with long-standing perinatally-acquired HIV infection in a recently-identified group of adolescents in Harare, Zimbabwe. These older children were not diagnosed early in life and so provide an opportunity to explore the underlying mechanisms of the human immune system related to delayed HIV disease progression.Studies have shown an enrichment of certain HLA alleles in adolescent long-term survivors of HIV-1 infection compared to healthy controls, but little is known about the role of other gene variants in delayed HIV-1 disease progression in this cohort of African children. The expression of protein variants involved in the peptide-loading complex of MHC class I or variants of other genes such as killer-cell immunoglobulin-like receptors (KIR) may play a role in long-term control of HIV-1 infection and should be investigated to build a picture of the host genetics which correlate with long-term survival of HIV. Defining and understanding the correlates of immune protection to HIV infection has the potential to aid in the design of vaccine and therapeutics to combat infection and disease. This is particularly important in developing regions of the world where the burden of HIV is highest.