A role for CD4 helper cells in HIV control and progression

Abstract

It remains unclear why HIV persists in most untreated individuals, and why a small minority of individuals can control the virus, either spontaneously or after an early treatment. The present work motivated by the striking differences in the functional avidity of CD4 T cells discovered between patient cohorts in a recent study [1] offers an experimentally–testable mathematical model that explains the diverse outcome of infection. The model predicts an arms race between viral dissemination and the proliferation of HIV-specific CD4 helper cells leading to one of two states: a low-viremia state or a high-viremia state. Helper CD4 cells with a higher avidity favor virus control. The parameter segregating spontaneous and post-treatment controllers is the infectivity asymmetry between activated and resting CD4 T cells. The predictions are found to be consistent with the data from [1] and with data on the avidity CD8 T cells [2]. I also analyze the alternative explanation of T cell exhaustion previously proposed to explain the diverse patient cohorts and demonstrate that it does not explain these and some other experimental data.ImportanceWhy HIV persists in most untreated individuals, and why a minority can control the virus, either spontaneously or after short treatment, remains unknown. The present study offers a mathematical model of the immune response that explains the differences between the patient cohorts as a result of the arms race between viral dissemination and the proliferation of HIV-specific CD4 T cells. It offers testable predictions and personalized adjustment of early ART to a patient.