title: CD4 T-Cell Responses in Primary HIV Infection: Interrelationship with Immune Activation and Virus Burden.
abstract: Early events during primary HIV infection (PHI) are thought to influence disease outcome. Although a growing body of evidence suggests a beneficial role of HIV-specific CD4 help in HIV infection, it is unclear how early viral replication, systemic immune activation, and antiretroviral therapy (ART) may shape CD4 T-cell responses during PHI, and whether HIV-specific CD4 responses contribute to the high immune activation observed in PHI. Twenty-seven patients with early PHI were included in a prospective longitudinal study and 12 of them received ART after enrollment. Fresh peripheral blood mononuclear cells were used for measurement ofex vivoT-cell activation and of cytokine-producing CD4 T-cells following stimulation with PMA/ionomycin or HIV-1-gag-p24 antigen. Patients were segregated based on CD8 T-cell activation level (i.e., % HLA-DR+CD38+CD8 T-cells) at baseline (BL). Patients with lower immune activation exhibited higher frequency of bulk CD4 T-cells producing IFN-γ or IL-17 and higher effector-to-regulatory cell ratios. No differences were found in HIV-specific CD4 T-cell frequencies. In contrast, segregation of patients based on plasma viral load (pVL) revealed that patients with higher pVL showed higher cytokine-producing HIV-specific CD4 responses. Of note, the frequency of IFN-γ+HIV-specific CD4 T cells significantly diminished between BL and month 6 only in ART-treated patients. However, early treatment initiation was associated with better maintenance of HIV-specific IFN-γ+CD4 T-cells. These data suggest that HIV-specific CD4 responses do not fuel systemic T-cell activation and are driven by viral replication but not able to contribute to its control in the early phase of infection. Moreover, our data also suggest a benefit of early treatment for the maintenance of HIV-specific CD4 T-cell help.
authors.affiliation: Institut Pasteur, Régulation des Infections Rétrovirales, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Mathieu F
authors.initials: MF
authors.lastname: Chevalier
authors.affiliation: Institut Pasteur, Régulation des Infections Rétrovirales , Paris , France.
authors.forename: Céline
authors.initials: C
authors.lastname: Didier
authors.affiliation: AP-HP, Hôpital Saint Antoine , Paris , France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou , Paris , France.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Manea
authors.affiliation: AP-HP, Hôpital Saint Antoine , Paris , France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Campa
authors.affiliation: Institut Pasteur, Régulation des Infections Rétrovirales , Paris , France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.affiliation: Institut Pasteur, Régulation des Infections Rétrovirales , Paris , France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott-Algara
authors.affiliation: Institut Pasteur, Régulation des Infections Rétrovirales, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
keywords: HIV-specific CD4 T cells; acute HIV infection; antiretroviral therapy; early ART initiation; generalized immune activation; viral load