title: Quantitative and qualitative differences in the T cell response to HIV in uninfected Ugandans exposed or unexposed to HIV-infected partners.
abstract: HIV-exposed and yet persistently uninfected individuals have been an intriguing, repeated observation in multiple studies, but uncertainty persists on the significance and implications of this in devising protective strategies against HIV. We carried out a cross-sectional analysis of exposed uninfected partners in a Ugandan cohort of heterosexual serodiscordant couples (37.5% antiretroviral therapy naive) comparing their T cell responses to HIV peptides with those of unexposed uninfected individuals. We used an objective definition of exposure and inclusion criteria, blinded ex vivo and cultured gamma interferon (IFN-γ) enzyme-linked immunospot assays, and multiparameter flow cytometry and intracellular cytokine staining to investigate the features of the HIV-specific response in exposed versus unexposed uninfected individuals. A response rate to HIV was detectable in unexposed uninfected (5.7%, 95% confidence interval [CI] = 3.3 to 8.1%) and, at a significantly higher level (12.5%, 95% CI = 9.7 to 15.4%, P = 0.0004), in exposed uninfected individuals. The response rate to Gag was significantly higher in exposed uninfected (10/50 [20.%]) compared to unexposed uninfected (1/35 [2.9%]) individuals (P = 0.0004). The magnitude of responses was also greater in exposed uninfected individuals but not statistically significant. The average number of peptide pools recognized was significantly higher in exposed uninfected subjects than in unexposed uninfected subjects (1.21 versus 0.47; P = 0.0106). The proportion of multifunctional responses was different in the two groups, with a higher proportion of single cytokine responses, mostly IFN-γ, in unexposed uninfected individuals compared to exposed uninfected individuals. Our findings demonstrate both quantitative and qualitative differences in T cell reactivity to HIV between HESN (HIV exposed seronegative) and HUSN (HIV unexposed seronegative) subject groups but do not discriminate as to whether they represent markers of exposure or of protection against HIV infection.
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda. pietro.pala@mrcuganda.org
authors.forename: Pietro
authors.initials: P
authors.lastname: Pala
authors.forename: Jennifer
authors.initials: J
authors.lastname: Serwanga
authors.forename: Christine
authors.initials: C
authors.lastname: Watera
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ritchie
authors.forename: Zoe
authors.initials: Z
authors.lastname: Moodie
authors.forename: Maggie
authors.initials: M
authors.lastname: Wang
authors.forename: Nilu
authors.initials: N
authors.lastname: Goonetilleke
authors.forename: Ester
authors.initials: E
authors.lastname: Birabwa
authors.forename: Peter
authors.initials: P
authors.lastname: Hughes
authors.forename: David
authors.initials: D
authors.lastname: Senkaali
authors.forename: Ritah
authors.initials: R
authors.lastname: Nakiboneka
authors.forename: Heiner
authors.initials: H
authors.lastname: Grosskurth
authors.forename: Bart
authors.initials: B
authors.lastname: Haynes
authors.forename: Andrew
authors.initials: A
authors.lastname: McMichael
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000096:biosynthesis; D058501:Enzyme-Linked Immunospot Assay; D005191:Family Characteristics; D005192:Family Health; D005260:Female; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology*; D006801:Humans; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D014454:Uganda
chemical_list: D016207:Cytokines