Host factors play an important role in determining rates of
disease progression in human immunodeficiency virus (HIV)-infected individuals. HIV is able to subvert the host immune system by infecting CD4+ T cells that normally orchestrate immune responses and by inducing the secretion of proinflammatory
cytokines that the virus can utilize to its own replicative advantage. The recognition that certain
chemokine receptors serve as necessary co-factors for HIV entry into its target cells as well as the fact that
ligands for these receptors can modulate the efficiency of
HIV infection has expanded the number and scope of host factors that may impact the pathogenesis of HIV disease. This area of investigation will no doubt yield novel therapeutic strategies for intervention in HIV disease; however, caution is warranted in light of the enormous complexity of the pleiotropic
cytokine and
chemokine networks and the uncertainty inherent in manipulating these systems. HIV-infected long-term non-progressors represent an excellent model to study potential host factors involved in HIV disease pathogenesis. Genetic factors certainly have a major impact on the immune responses mounted by the host. In this regard, a polymorphism in the gene for the HIV co-receptor
CC chemokine receptor 5 (CCR5), which serves as a co-receptor for macrophage (M)-tropic strains of HIV, affords a high degree of protection against
HIV infection in individuals homozygous for the genetic defect and some degree of protection against
disease progression in HIV-infected heterozygotes. HIV-specific immune responses, including cytotoxic T-lymphocyte (CTL) responses and
neutralizing antibody responses, also appear to play salutary roles in protecting against
disease progression.