The rationale for immunosuppressive therapy for HIV infection

This article reviews the characteristics of HIV-associated immune activation, describes its prognostic significance and highlights the lack of knowledge of the mechanism by which HIV-1 infection induces this phenomenon.

A recent cohort analysis found that the level of HIV-1 RNA in plasma has only minimal predictive value for the rate of decline of the CD4+ T-lymphocyte count in an individual patient infected with HIV-1. This suggests that factors in addition to viral replication must play an important role in the genesis of immune deficiency in HIV-1 infection, and has rekindled interest in the generalized T-cell activation induced by HIV-1 infection and the apoptosis that results as the likely culprit.

Measures of T-cell activation provide independent and, in some studies, more powerful, prognostic information as to the course of HIV-1 disease compared with the viral load. The case is made for focused studies of immune suppression carefully designed to decipher the mechanism(s) involved in HIV-associated immune activation and to develop unique therapies aimed at treating the pathogenic consequences of HIV-1 infection. Given its prognostic significance, the reduction of immune activation is an important goal of the therapy of HIV-1 infection.