Host factors associated with outcome from primary human immunodeficiency virus-1 infection

Abstract

The early events in human immunodeficiency virus-1 infection are increasingly recognized as critical for the overall evolution of the disease. Viral and host factors interact to establish a point of equilibrium defined by the viral set point. This review highlights new opportunities in the understanding of the genetic and genomic determinants of those early events. The field of human immunodeficiency virus host genetics is shifting from the measure of long-term consequences of infection to the analysis of quantitative biological endpoints of viral control, with particular attention on the earliest events as study phenotypes. The field has also been enriched by a better understanding of the determinant and complex role of human leukocyte antigen and killer cell immunoglobulin-like-receptor variation, and by the completion of the first genome-wide study of determinants of human immunodeficiency virus-1 replication. The genome analysis highlights the central influence of acquired immunity in viral control, and provides an extensive catalogue of novel gene candidates. Host genetics and genomic analyses of precise quantitative study phenotypes offer an unprecedented opportunity to dissect critical steps in human immunodeficiency virus-1 pathogenesis.