title: HIV-1-specific enzyme-linked immunosorbent spot assay responses in HIV-1-exposed uninfected partners in discordant relationships compared to those in low-risk controls.
abstract: A number of studies of highly exposed HIV-1-seronegative individuals (HESN) have found HIV-1-specific cellular responses. However, there is limited evidence that responses prevent infection or are linked to HIV-1 exposure. Peripheral blood mononuclear cells (PBMC) were isolated from HESN in HIV-1-discordant relationships and low-risk controls in Nairobi, Kenya. HIV-1-specific responses were detected using gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assays stimulated by peptide pools spanning the subtype A HIV-1 genome. The HIV-1 incidence in this HESN cohort was 1.5 per 100 person years. Positive ELISpot responses were found in 34 (10%) of 331 HESN and 14 (13%) of 107 low-risk controls (odds ratio [OR] = 0.76; P = 0.476). The median immunodominant response was 18.9 spot-forming units (SFU)/10(6) peripheral blood mononuclear cells (PBMC). Among HESN, increasing age (OR = 1.24 per 5 years; P = 0.026) and longer cohabitation with the HIV-1-infected partner (OR = 5.88 per 5 years; P = 0.003) were associated with responses. These factors were not associated with responses in controls. Other exposure indicators, including the partner's HIV-1 load (OR = 0.99 per log(10) copy/ml; P = 0.974) and CD4 count (OR = 1.09 per 100 cells/μl; P = 0.238), were not associated with responses in HESN. HIV-1-specific cellular responses may be less relevant to resistance to infection among HESN who are using risk reduction strategies that decrease their direct viral exposure.
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington, USA.
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Guthrie
authors.forename: Barbara
authors.initials: B
authors.lastname: Lohman-Payne
authors.forename: Amy Y
authors.initials: AY
authors.lastname: Liu
authors.forename: Rose
authors.initials: R
authors.lastname: Bosire
authors.forename: Samuel Victor
authors.initials: SV
authors.lastname: Nuvor
authors.forename: Robert Y
authors.initials: RY
authors.lastname: Choi
authors.forename: Romel D
authors.initials: RD
authors.lastname: Mackelprang
authors.forename: James N
authors.initials: JN
authors.lastname: Kiarie
authors.forename: Stephen C
authors.initials: SC
authors.lastname: De Rosa
authors.forename: Barbra A
authors.initials: BA
authors.lastname: Richardson
authors.forename: Grace C
authors.initials: GC
authors.lastname: John-Stewart
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
mesh_terms: D000328:Adult; D000367:Age Factors; D058501:Enzyme-Linked Immunospot Assay / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007630:Kenya; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D012747:Sexual Partners; D013997:Time Factors
chemical_list: D007371:Interferon-gamma