title: HIV-1-specific CD4+ T cell responses in chronically HIV-1 infected blippers on antiretroviral therapy in relation to viral replication following treatment interruption.
abstract: The impact of transient viral load blips on anti-HIV-1 immune responses and on HIV-1 rebound following treatment interruption (TI) is not known. Clinical and immunological parameters were measured during 40 weeks of antiretroviral therapy (ART) and following TI in an observational cohort of 16 chronically HIV-1-infected subjects with or without observed viral load blips during ART. During therapy, blips in seven subjects were associated with higher anti-HIV-1 (p24) CD4+ T cell lymphoproliferative responses (p = 0.04), without a significant difference in T cell activation or total anti-HIV-1 CD8+ T cell interferon-gamma (IFN-gamma) responses when compared to nine matched non-blippers. Therapy interruption resulted in a significantly higher viral rebound in blippers by 8 week despite retention of higher lymphoproliferative p24 responses (p = 0.01) and a rise in CD3+ T cell activation (p = 0.04) and anti-HIV-1 CD8+ T cell responses in blippers by week 4 when compared to non-blippers. Past week 4 of interruption, therapy re-initiation criteria were also met by a higher frequency in blippers by week 14 (p < 0.04) with no difference between groups by week 24. These data support that blippers have higher anti-HIV lymphoproliferative responses while on ART but experience equal to higher viral rebound as compared to matched non-blippers upon TI.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA. montaner@wistar.org
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Papasavvas
authors.forename: Jay R
authors.initials: JR
authors.lastname: Kostman
authors.forename: Brian
authors.initials: B
authors.lastname: Thiel
authors.forename: Maxwell
authors.initials: M
authors.lastname: Pistilli
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Mackiewicz
authors.forename: Andrea
authors.initials: A
authors.lastname: Foulkes
authors.forename: Robert
authors.initials: R
authors.lastname: Gross
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Jordan
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Robert
authors.initials: R
authors.lastname: Grant
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Poulin
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
authors.forename: Karam
authors.initials: K
authors.lastname: Mounzer
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012367:RNA, Viral / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral