title: Comprehensive analysis of unique cases with extraordinary control over HIV replication.
abstract: True long-term nonprogressors (LTNPs)/elite controllers (ECs) maintain durable control over HIV replication without antiretroviral therapy. Herein we describe 4 unique persons who were distinct from conventional LTNPs/ECs in that they had extraordinarily low HIV burdens and comparatively weak immune responses. As a group, typical LTNPs/ECs have unequivocally reactive HIV-1 Western blots, viral loads below the lower threshold of clinical assays, low levels of persistent viral reservoirs, an over-representation of protective HLA alleles, and robust HIV-specific CD8(+) T-cell responses. The 4 unique cases were distinguished from typical LTNPs/ECs based on weakly reactive Western blots, undetectable plasma viremia by a single copy assay, extremely low to undetectable HIV DNA levels, and difficult to isolate replication-competent virus. All 4 had at least one protective HLA allele and CD8(+) T-cell responses that were disproportionately high for the low antigen levels but comparatively lower than those of typical LTNPs/ECs. These unique persons exhibit extraordinary suppression over HIV replication, therefore, higher-level control than has been demonstrated in previous studies of LTNPs/ECs. Additional insight into the full spectrum of immune-mediated suppression over HIV replication may enhance our understanding of the associated mechanisms, which should inform the design of efficacious HIV vaccines and immunotherapies.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mendoza
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Johnson
authors.forename: Bennett A
authors.initials: BA
authors.lastname: Peterson
authors.forename: Ven
authors.initials: V
authors.lastname: Natarajan
authors.forename: Maria
authors.initials: M
authors.lastname: Salgado
authors.forename: Robin L
authors.initials: RL
authors.lastname: Dewar
authors.forename: Peter D
authors.initials: PD
authors.lastname: Burbelo
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Doria-Rose
authors.forename: Erin H
authors.initials: EH
authors.lastname: Graf
authors.forename: Jamieson H
authors.initials: JH
authors.lastname: Greenwald
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Hodge
authors.forename: William L
authors.initials: WL
authors.lastname: Thompson
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Cogliano
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Chairez
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Rehm
authors.forename: Sara
authors.initials: S
authors.lastname: Jones
authors.forename: Claire W
authors.initials: CW
authors.lastname: Hallahan
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.forename: Omar
authors.initials: O
authors.lastname: Sued
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Peel
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Connell
authors.forename: Una
authors.initials: U
authors.lastname: O'Doherty
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Migueles
mesh_terms: D000328:Adult; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D006679:HIV Seropositivity / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology / Q000502:physiology