title: Induction of Gag-specific CD4 T cell responses during acute HIV infection is associated with improved viral control.
abstract: Effector CD4 T cell responses have been shown to be critically involved in the containment and clearance of viral pathogens. However, their involvement in the pathogenesis of HIV infection is less clear, given their additional role as preferred viral targets. We previously demonstrated that the presence of HIV-specific CD4 T cell responses is somewhat associated with HIV control and that specific CD4 T cell functions, such as direct cytolytic activity, can contribute to control of HIV viremia. However, little is known about how the induction of HIV-specific CD4 T cell responses during acute HIV infection influences disease progression and whether responses induced during the early phase of infection are preferentially depleted. We therefore longitudinally assessed, in a cohort of 55 acutely HIV-infected individuals, HIV-specific CD4 T cell responses from acute to chronic infection. Interestingly, we found that the breadth, magnitude, and protein dominance of HIV-specific CD4 T cell responses remained remarkably stable over time. Moreover, we found that the epitopes targeted at a high frequency in acute HIV infection were recognized at the same frequency by HIV-specific CD4 T cells in chronic HIV infection. Interestingly the induction of Gag-specific CD4 T cell responses in acute HIV infection was significantly inversely correlated with viral set point in chronic HIV infection (R = -0.5; P = 0.03), while the cumulative contribution of Env-specific CD4 T cell responses showed the reverse effect. Moreover, individuals with HIV-specific CD4 T cell responses dominantly targeting Gag over Env in acute HIV infection remained off antiretroviral therapy significantly longer (P = 0.03; log rank). Thus, our data suggest that the induction of HIV-specific CD4 T cell responses during acute HIV infection is beneficial overall and does not fuel disease progression.
  
  
  OBJECTIVE
  CD4 T cells are critical for the clearance and control of viral infections. However, HIV preferentially infects HIV-specific CD4 T cells. Thus, their contribution to the control of HIV viremia is uncertain. Here, we study HIV-specific CD4 T cell responses from acute to chronic HIV infection and show that the generation of certain CD4 responses is associated with control rather than disease progression.
authors.affiliation: HIV Clinic Praxis Jessen, Berlin, Germany Institute for Microbiology and Hygiene, Charité University Medical Center, Berlin, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Schieffer
authors.affiliation: HIV Clinic Praxis Jessen, Berlin, Germany.
authors.forename: Heiko K
authors.initials: HK
authors.lastname: Jessen
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Oster
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors.forename: Franco
authors.initials: F
authors.lastname: Pissani
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachussetts, USA.
authors.forename: Damien Z
authors.initials: DZ
authors.lastname: Soghoian
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Lu
authors.affiliation: HIV Clinic Praxis Jessen, Berlin, Germany.
authors.forename: Arne B
authors.initials: AB
authors.lastname: Jessen
authors.affiliation: HIV Clinic Praxis Jessen, Berlin, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Zedlack
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Schultz
authors.affiliation: HIV Clinic Praxis Jessen, Berlin, Germany.
authors.forename: Isaiah
authors.initials: I
authors.lastname: Davis
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachussetts, USA.
authors.forename: Srinika
authors.initials: S
authors.lastname: Ranasinghe
authors.affiliation: Massachussetts General Hospital, Boston, Massachussetts, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachussetts, USA.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.affiliation: Institute for Microbiology and Hygiene, Charité University Medical Center, Berlin, Germany.
authors.forename: Ralf R
authors.initials: RR
authors.lastname: Schumann
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachussetts, USA hstreeck@hivresearch.org.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D002908:Chronic Disease; D018450:Disease Progression; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006679:HIV Seropositivity; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016056:Immunodominant Epitopes; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D019562:Viral Load / Q000276:immunology*; D014766:Viremia / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D016056:Immunodominant Epitopes
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