title: Infrequent detection of HIV-1-specific, but not cytomegalovirus-specific, CD8(+) T cell responses in young HIV-1-infected infants.
abstract: Early potent combination antiretroviral therapies (ART) for HIV-1 infection can preserve or restore immune function, but control of viral replication early in infection may interfere with the development of HIV-1-specific immune responses. Using an IFN-gamma ELISPOT assay, we evaluated the breadth and intensity of HIV-1-specific CD8(+) T cell responses in 17 vertically infected infants who began ART at 1-23 mo of age. CMV-specific responses were also characterized in three infants coinfected with HIV-1 and CMV. Before ART, HIV-1-specific CD8(+) T cell responses were detected in two of 13 (15%) infants <6 mo of age. HIV-1-specific CD8(+) T cells became undetectable in these two infants after the control of viral replication. Intermittent HIV-1-specific responses were noted in six infants who did not experience durable control of viral replication. In contrast, HIV-1-specific responses were detected before ART in four of four infants >6 mo of age and became persistently undetectable in only one child. CMV-specific CD8(+) T cell responses were persistently detected in all HIV-1 and CMV coinfected infants. In conclusion, HIV-1-specific CD8(+) T cell responses were less commonly detected before therapy in young infants than in older infants. Suppression of viral replication appeared to interfere with the development and maintenance of HIV-1-specific CD8(+) T cell responses. The detection of CMV-specific responses in HIV-1 and CMV coinfected infants suggests a selective defect in the generation or maintenance of HIV-1-specific CD8(+) T cell responses. Therapeutic HIV-1 vaccine strategies in young infants may prolong the clinical benefit of ART by expanding the HIV-1-specific CD8(+) T cell pool.
authors.affiliation: Graduate Program in Immunology/Virology and Department of Pediatrics and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Z A
authors.initials: ZA
authors.lastname: Scott
authors.forename: E G
authors.initials: EG
authors.lastname: Chadwick
authors.forename: L L
authors.initials: LL
authors.lastname: Gibson
authors.forename: M D
authors.initials: MD
authors.lastname: Catalina
authors.forename: M M
authors.initials: MM
authors.lastname: McManus
authors.forename: R
authors.initials: R
authors.lastname: Yogev
authors.forename: P
authors.initials: P
authors.lastname: Palumbo
authors.forename: J L
authors.initials: JL
authors.lastname: Sullivan
authors.forename: P
authors.initials: P
authors.lastname: Britto
authors.forename: H
authors.initials: H
authors.lastname: Gay
authors.forename: K
authors.initials: K
authors.lastname: Luzuriaga
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D015488:HIV Antigens; D007371:Interferon-gamma