How HIV causes disease

The correlates of disease are easier to identify than the correlates of protection and have been well documented by many investigators. Studies on the early stages of disease at the time of infection and seroconversion show that the viral load and the nonspecific activation markers of the immune system such as soluble TNF receptor levels are both highest in those that progress to disease rapidly. However, even in those who progress rapidly towards disease the high initial virus load is quickly reduced, presumably by the immune response, although the intrinsic dynamics of viral replication could also explain at least part of the decline. It may be that the initial interaction between the virus and the immune response sets the future pattern of disease. The issues affecting the establishment of infection at this stage are numerous and include properties of the virus as well as the host. Nonspecific sera and complement factors may play an initial role and the responsive ness of the immune system is probably also critical. A number of studies have reported a strong link between HIV disease progression and nonspecific activation of the immune system. Not only is there a close association with the rate of progression to disease, but also the baseline activation associated with immunogenetic markers such as the HLA system itself determines the rate of disease progression.

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