title: Delayed differentiation of potent effector CD8+T cells reducing viremia and reservoir seeding in acute HIV infection.
abstract: CD8+T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The simian immunodeficiency virus model provided the proof of concept for a CD8+T cell-mediated reservoir clearance but showed conflicting evidence on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8+T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. We studied HIV-specific CD8+T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI). We showed that the HIV-specific CD8+T cells generated as early as AHI stages 1 and 2 before peak viremia are delayed in expanding and acquiring effector functions but are endowed with higher memory potential. In contrast, the fully differentiated HIV-specific CD8+T cells at peak viremia in AHI stage 3 were more prone to apoptosis but were associated with a steeper viral load decrease after ART initiation. Their capacity to persist in vivo after ART initiation correlated with a lower HIV DNA reservoir. These findings demonstrate that HIV-specific CD8+T cell magnitude and differentiation are delayed in the earliest stages of infection. These results also demonstrate that potent HIV-specific CD8+T cells contribute to the reduction of the pool of HIV-producing cells and the HIV reservoir seeding in vivo and provide the rationale to design interventions aiming at inducing these potent responses to cure HIV infection.
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
authors.forename: Hiroshi
authors.identifier: 0000-0003-1457-6919
authors.initials: H
authors.lastname: Takata
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.|Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Supranee
authors.initials: S
authors.lastname: Buranapraditkun
authors.affiliation: The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Cari
authors.identifier: 0000-0003-1315-9734
authors.initials: C
authors.lastname: Kessing
authors.affiliation: SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: James L K
authors.initials: JL
authors.lastname: Fletcher
authors.affiliation: Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University, Philadelphia, PA 19102, USA.
authors.forename: Roshell
authors.initials: R
authors.lastname: Muir
authors.affiliation: Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University, Philadelphia, PA 19102, USA.
authors.forename: Virginie
authors.identifier: 0000-0001-5604-6524
authors.initials: V
authors.lastname: Tardif
authors.affiliation: School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Pearline
authors.initials: P
authors.lastname: Cartwright
authors.affiliation: Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, FL 34987, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Vandergeeten
authors.affiliation: Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, FL 34987, USA.
authors.forename: Wendy
authors.identifier: 0000-0002-5350-7150
authors.initials: W
authors.lastname: Bakeman
authors.affiliation: Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, FL 34987, USA.
authors.forename: Carmen N
authors.identifier: 0000-0001-7949-2455
authors.initials: CN
authors.lastname: Nichols
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
authors.forename: Suteeraporn
authors.identifier: 0000-0003-3880-4381
authors.initials: S
authors.lastname: Pinyakorn
authors.affiliation: Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.|Nuffield Department of Medicine, University of Oxford, Oxford, U.K.
authors.forename: Pokrath
authors.initials: P
authors.lastname: Hansasuta
authors.affiliation: SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Eugene
authors.initials: E
authors.lastname: Kroon
authors.affiliation: SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Thep
authors.initials: T
authors.lastname: Chalermchai
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Robert
authors.initials: R
authors.lastname: O'Connell
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Jerome
authors.identifier: 0000-0003-0461-6438
authors.initials: J
authors.lastname: Kim
authors.affiliation: SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
authors.forename: Merlin L
authors.identifier: 0000-0003-3949-9649
authors.initials: ML
authors.lastname: Robb
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Nelson L
authors.identifier: 0000-0001-5882-5548
authors.initials: NL
authors.lastname: Michael
authors.affiliation: Department of Microbiology, Infectiology, and Immunology, Centre de Recherche Hospitalier de l'Université de Montréal, Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.affiliation: Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University, Philadelphia, PA 19102, USA.
authors.forename: Elias K
authors.identifier: 0000-0002-4537-8301
authors.initials: EK
authors.lastname: Haddad
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.|SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. ltrautmann@hivresearch.org.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
authors.forename: Lydie
authors.identifier: 0000-0002-3012-0009
authors.initials: L
authors.lastname: Trautmann
mesh_terms: D000208:Acute Disease; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004197:Disease Reservoirs / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D006801:Humans; D008297:Male; D016019:Survival Analysis; D019562:Viral Load; D014766:Viremia / Q000276:immunology* / Q000821:virology
chemical_list: D016207:Cytokines