Quantitative and qualitative differences in the T cell response to HIV in uninfected Ugandans exposed or unexposed to HIV infected partners.

Publication Type:

Journal Article

Source:

Journal of virology (2013)

Keywords:

2013, June 2013, Vaccine and Infectious Disease Division

Abstract:

HIV exposed and persistently uninfected individuals have been an intriguing, repeated observation in multiple studies, but uncertainty persists on their significance and implications for 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% ART naïve) 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 IFN-γ ELISPOTs and multiparameter flow cytometry 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% C.I.: 3.3 -8.1%) and, at a significantly higher level (12.5%, 95% C.I.: 9.7-15.4%), 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%), p=0.0004. The magnitude of responses was also higher in exposed uninfected but not statistically significant. The average number of peptide pools recognized was significantly higher in exposed uninfected (1.21) than in unexposed uninfected (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 compared to exposed uninfected. Our findings demonstrate both quantitative and qualitative differences in T cell reactivity to HIV between HESN and HUSN but do not discriminate whether they represent markers of exposure or of protection against HIV infection.