Bruce D Walker

Immune Control in HIV infection:  Predictability in the Midst of Chaos

Background:  The immunologic correlates of protection from disease progression remain to be defined 2 decades after the discovery of neutralizing antibodies and cytotoxic T cells specific for HIV. The most revealing studies of immune control of chronic viral infections come from mouse studies using cloned viruses and inbred mouse strains; in these models a simple change in virus sequence of 2 amino acids can result in an entirely different outcome of disease, when everything else is held constant. The task of understanding HIV immunopathogenesis is difficult because of the tremendous viral diversity among and within clades, marked HLA heterogeneity among infected persons, and different durations of infection.

Conclusions:  Using transmission pairs to control for the infecting virus, acute infection to control for duration of infection, and large population studies to control for viral and host genetic heterogeneity, it is clear that there is considerable predictability in the virus–host interaction, and that there are constraints on viral  evolution under immune selection pressure. Such studies indicate that adaptive immune responses vary in their antiviral efficacy, and suggest that it may be possible to develop immunogens that represent the predictable variants that will arise under immune selection pressure.