Anti-HIV adaptive immunity: determinants for viral persistence.

The immense difficulty in primary control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection by adaptive immune responses has been a topic of exceptional importance. CD8+ cytotoxic T lymphocytes (CTLs) do play a central role in primary resolution of viremia, but their potency in viral control is generally constrained in the natural courses of HIV/SIV infections. The overall repertoire of CTLs is dependent on both the host and the virus genetic polymorphisms, and the potency of each individual CTL is affected by immunological and virological determinants. HIV/SIV infections lack early appearance of neutralising antibodies (NAbs), and our recent finding has suggested a possibility of their absence contributing to diminished virus-specific CD4+ T-cell responses leading to failure in primary viral control. Extrapolations from studies in macaque models of SIV infection and analyses of the cohorts of HIV control in humans have to date delineated the numerous requirements for attainment of viral control. Understanding of the individual components of adaptive immune responses and their optimal concert required for HIV/SIV control would contribute to development of an effective AIDS vaccine. Here, we discuss current insights into CTLs and NAbs, and speculate their possible protective mechanism against establishment of persistent HIV/SIV infection. Copyright (c) 2008 John Wiley & Sons, Ltd.