title: Pediatric HIV-1-specific cytotoxic T-lymphocyte responses suggesting ongoing viral replication despite combination antiretroviral therapy.
abstract: Human immunodeficiency virus-1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL) responses are common in infected adults and usually exhibit rapid decay after combination antiretroviral therapy (ART). CTLs develop later in the first year of life, and the fate of HIV-1-specific responses in perinatally infected children after ART is less well described. HIV-1-specific CTL responses were measured in 17 perinatally infected children and adolescents (ages 3-20 y) receiving combination ART. Seven had prolonged viral suppression (<400 copies/mL) for 2.5-5.3 y and 10 had persistent viremia (median, 77,550 copies/mL). HIV-1-specific CTL responses were tested by interferon (IFN)-gamma enzyme-linked immunospot (ELIS-pot) assays using 53 overlapping peptide pools spanning the entire HIV-1 proteome. HIV-1-specific CTL responses were detected in 14 of 17 individuals. Responses to one to four viral proteins were found in eight of 10 individuals with persistent viremia and six of seven with prolonged viral suppression. The magnitude and breadth of CTL responses were similar between groups. HIV-1-specific CTL responses were present in the majority of perinatally infected subjects, irrespective of viremia at evaluation. Because ART-treated infected adults usually have rapid decay of responses, these data suggest viral replication below the limits of detection is more persistent in combination ART-treated perinatally infected pediatric subjects. The long-term clinical implications of these findings remain to be determined.
authors.affiliation: Department of Pediatrics, Division of Pediatric Infectious Diseases, David Gefen School of Medicine at UCLA and Mattel Children's Hospital at UCLA, Los Angeles, California 90095, USA. nching@mednet.ucla.edu
authors.forename: Natascha
authors.initials: N
authors.lastname: Ching
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.forename: Jaime G
authors.initials: JG
authors.lastname: Deville
authors.forename: Karin
authors.initials: K
authors.lastname: Nielsen-Saines
authors.forename: Bonnie J
authors.initials: BJ
authors.lastname: Ank
authors.forename: Myung-Shin
authors.initials: MS
authors.lastname: Sim
authors.forename: Yvonne J
authors.initials: YJ
authors.lastname: Bryson
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D002648:Child; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D008297:Male; D010455:Peptides / Q000494:pharmacology; D012191:Retroviridae Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D010455:Peptides; D012191:Retroviridae Proteins; D007371:Interferon-gamma