Faroudy Boufassa, Daniela Benati, Pierre de Truchis, Patricia Jeannin, Fabrice Lemaître, Moran Galperin, Lisa A. Chakrabarti, Jacques Thèze, Laurence Slama, William W. Kwok, Olivier Lambotte, Jean-François Delfraissy, Benoît Vingert, Santiago Perez-Patrigeon, Immunogénétique Cellulaire, Institut Pasteur [Paris] (IP), Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital Raymond Poincaré [AP-HP], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Santé reproductive, sexualité, infection à VIH - épidémiologie, démographie, sciences sociales, Institut national d'études démographiques (INED)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Benaroya Research Institute, Virginia Mason, Dynamiques des Réponses Immunes, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS, study EP36-3) and the Pasteur Institute, Paris, France. B.V. was the recipient of a Sidaction fellowship. D.B. and M.G. are the recipients of ANRS fellowships., Institut Pasteur [Paris], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, AP-HP Hôpital Raymond Poincaré [Garches], CHU Tenon [APHP], Institut national d'études démographiques ( INED ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM )
HIV controllers are rare individuals who spontaneously control HIV replication in the absence of antiretroviral therapy. To identify parameters of the CD4 response that may contribute to viral control rather than merely reflect a persistently low viremia, we compared the T helper profiles in two groups of patients with more than 10 years of viral suppression: HIV controllers from the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO18 cohort ( n = 26) and efficiently treated patients ( n = 16). Cells specific for immunodominant Gag and cytomegalovirus (CMV) peptides were evaluated for the production of 10 cytokines and cytotoxicity markers and were also directly quantified ex vivo by major histocompatibility complex (MHC) class II tetramer staining. HIV controller CD4 + T cells were characterized by a higher frequency of gamma interferon (IFN-γ) production, perforin + /CD107a + expression, and polyfunctionality in response to Gag peptides. While interleukin 4 (IL-4), IL-17, and IL-21 production did not differ between groups, the cells of treated patients produced more IL-10 in response to Gag and CMV peptides, pointing to persistent negative immunoregulation after long-term antiretroviral therapy. Gag293 tetramer-positive cells were detected at a high frequency (0.12%) and correlated positively with IFN-γ-producing CD4 + T cells in the controller group ( R = 0.73; P = 0.003). Tetramer-positive cells were fewer in the highly active antiretroviral therapy (HAART) group (0.04%) and did not correlate with IFN-γ production, supporting the notion of a persistent immune dysfunction in HIV-specific CD4 + T cells of treated patients. In conclusion, HIV controllers maintained a population of highly efficient Th1 effectors directed against Gag in spite of a persistently low antigenemia, while patients treated in the long term showed a loss of CD4 effector functions.