title: HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.
abstract: Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.
authors.affiliation: Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02129, USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Mary N
authors.initials: MN
authors.lastname: Johnston
authors.forename: Deepak
authors.initials: D
authors.lastname: Agrawal
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Ben T
authors.initials: BT
authors.lastname: Davis
authors.forename: Paul K
authors.initials: PK
authors.lastname: Lee
authors.forename: Erica L
authors.initials: EL
authors.lastname: Maier
authors.forename: Jason
authors.initials: J
authors.lastname: Harlow
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D000595:Amino Acid Sequence; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015488:HIV Antigens / Q000737:chemistry / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry / Q000145:classification / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010802:Phylogeny; D015163:Superinfection / Q000276:immunology* / Q000821:virology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000276:immunology / Q000821:virology; D014779:Virus Replication
chemical_list: D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D007371:Interferon-gamma