Cartesian coordinate analysis of viral burden and CD4+ cell count in HIV disease: implications for clinical trial...

HIV-1 infection represents a dynamic interaction between the rapid turnover of virus, CD4+ cell proliferation and clearance. HIV-1 disease progression is assessed, in part, by the inverse relationship between virus burden and CD4+ cell count. However, there is enormous individual subject variability between virus burden in the peripheral blood and CD4+ cell count with subsequent disease progression, suggesting that there must be virologic and immunologic modifiers of the inverse relationship between virus load and CD4+ cell count. To investigate these modifiers, we have used a Cartesian coordinate plot analysis to describe the inverse relationship between viral burden and the peripheral blood CD4+ cell count. Subjects from several clinical studies with CD4+ cell counts ranging from < 50 to > 600 cells/microL and varying viral burdens were studied. The analysis described the effect of various virologic and immunologic modifiers on this inverse relationship, for example, viral resistance, viral phenotype and the effect of very low CD4+ cell counts, and specifically addressed individual subject variation in assessing the association between the viral and immunologic parameters that define disease progression and response to antiretroviral therapy. As such, the Cartesian coordinate plot analysis method provides one approach to investigating the individual subject response to antiretroviral therapy.