Host genetic determinants of human immunodeficiency virus infection and disease progression in children

Increasing data support host genetic factors as an important determinants of human immunodeficiency virus type-1 (HIV-1) susceptibility, mother-to-child transmission (MTCT), and disease progression. Of these genetic mediators, those impacting innate and adaptive immune responses seem to play a critical role in viral infectivity and pathogenesis. During primary infection, CCR5 using virus is predominantly transmitted and polymorphisms that affect the expression of CCR5 alter the risk for MTCT and rate of disease. Chemokines that naturally bind to coreceptors alter infectivity and viral pathogenesis. Additional genes that affect innate immunity including those encoding for MBL2 and those modulating the adaptive immune response including CX3CR1 and human leukocyte antigen types can significantly modify susceptibility and response to HIV-1 infection. As young children develop, the dependence on certain arms of the immune system varies and can alter the effect of genetic variants. Additionally, host genetic factors may alter the response to antiretrovirals. Finally, because HIV-infected children progress more rapidly than adults and have fewer background cofactors, such as drug use and coinfections, the effects of host factors on HIV-1 disease may be more clearly identified. In this review, we summarize available data on the impact of host genetics on MTCT and disease progression of HIV-infected children.