More recently, studies largely conducted in animal models highlighted the importance of discriminating between three major HIV disease states: acute infection (where antiviral factors are upregulated), chronic ART-untreated infection (where both permanent low-level ISG expression and CD4 T cell depletion are maintained), and chronic ART-treated infection (where CD4 T cell recovery occurs and inflammation is at its lowest—albeit not normalized). Here, CD4 is linked to infection.