title: HIV-specific gag responses in early infancy correlate with clinical outcome and inversely with viral load.
abstract: Many HIV-infected infants progress to AIDS during the first year of life when antiretroviral therapy (ART) is not given. The immune determinants of progression to AIDS are not known. We hypothesized that distinct HIV-specific T cell responses correlate with viral load and survival over the first year of life. Whole blood of infants at 3, 6, 9, and 12 months of age was incubated with HIV antigens Gag and Env. The frequency of specific T cells producing interferon (IFN)-γ was then measured by flow cytometry. Viral load and CD4% in HIV(+) infants were determined at each time point. ART was not available for this population at the time of sample collection. Those infants who survived to 12 months of age (n=12) had lower viral loads and higher Gag-specific CD8(+) T cell responses at 3 months, compared with infants who died (n=8). Furthermore, the frequency of Gag-specific CD4(+) T cells correlated inversely with viral load at 3 and 6 months of age. Together these data indicate that the early presence of quantitatively higher Gag-specific T cell responses in HIV-infected infants is associated with lower viral loads and decreased mortality in the first year of life. Our data support the design of a vaccine that preferentially elicits Gag responses, which may result in lower levels of viremia and possibly improve outcome.
authors.affiliation: South African Tuberculosis Vaccine Initiative, School of Child and Adolescent Health and Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory.
authors.forename: Bongeka
authors.initials: B
authors.lastname: Nqoko
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Day
authors.forename: Nazma
authors.initials: N
authors.lastname: Mansoor
authors.forename: Marwou
authors.initials: M
authors.lastname: De Kock
authors.forename: E Jane
authors.initials: EJ
authors.lastname: Hughes
authors.forename: Tony
authors.initials: T
authors.lastname: Hawkridge
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Hussey
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D015686:Gene Products, env / Q000276:immunology; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis; D016896:Treatment Outcome; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015686:Gene Products, env; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma