CD4 and HIV infectious disease: Accordingly, as in the first episode of VL CD4+ count was already low, the data suggest that CD4+ depletion antecedes CD8+ loss, denoting a two-step process in which CD4+ reduction is initially dependent on HIV infection, allowing L. infantum proliferation and worsening inflammation and finally leading to CD8+ loss and reduced function, increasing immunosuppression, and causing future relapses.