Analysis of the effect of highly active antiretroviral therapy during acute HIV-1 infection on HIV-specific CD4 T cell functions

Abstract

It has been reported that antiretroviral therapy (HAART) during acute HIV-1 infection may rescue HIV-1-specific CD4 T cell responses. To determine the duration of this preserved response by investigating the long-term effects of HAART during acute infection on HIV-specific CD4 T cell function related to possible immune control during subsequent therapy interruption. A longitudinal analysis followed HIV-specific CD4 T cell reactivity in 17 individuals with well-documented acute HIV-1 infection where five out of 11 HAART-treated patients stopped therapy and six were untreated. Peripheral blood mononuclear cells were stimulated with overlapping peptide pools derived from Gag and Nef. Production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) by CD4 T cells was analysed together with proliferative responses. Absolute numbers, but not percentages, of Gag-specific IFN-gamma-, IL-2- or IFN-gamma/IL-2-producing CD4 T cells were increased in treated compared with untreated individuals up to 2 years after seroconversion. HAART during acute HIV-1 infection was associated with lower viral load but did not result in increased proliferation of HIV-specific CD4 T cells. One out of five individuals who discontinued therapy showed evidence for immune control. However, patients who failed to control viraemia also had measurable proliferative HIV-specific CD4 T cell responses and preserved numbers of cytokine-producing CD4 T cells. Early HAART during acute HIV-1 infection resulted in higher numbers of HIV-specific IFN-gamma- and IL-2-producing CD4 T cells, but this preservation in four out of five patients was not associated with control of viraemia upon treatment interruption.