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We have used a Cartesian coordinate plot to analyze the inverse relationship between viral burden (x-axis) and peripheral blood CD4+ cell count (y-axis) to extend our understanding of the mechanisms of antiviral drugs and differences in outcome resulting from variability in virus and host responses. Each of 186 subjects studied were assigned to one of four response quadrants. Quadrants A (x-, y+) and D (x+, y-) defined the effect of a change in virus load on the inverse change in CD4+ cell count expected from the natural history of HIV infection or antiretroviral therapy. Quadrants B (x+, y+) and C (x-, y-) defined the dissociation of the inverse relationship between the relative changes in CD4+ cell count and viral load that resulted from the hypothesized effect of putative virologic or immunologic response modifiers. Of the response modifiers studied, only the syncytium-inducing phenotype resulted in a complete dissociation of this inverse relationship. The analysis provided an integrated virological and immunological approach to better understand therapeutic responses and potential dissociation between changes in viral RNA and CD4+ cell count. This type of analysis may be helpful for individualizing patient management as well as designing and analyzing studies of HIV-1 antiretroviral drugs and disease pathogenesis. |
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