Journal of Clinical and Cellular Immunology
Open Access

CD8+ T cell dynamics in untreated and treated hyperacute HIV infection: Implications for HIV vaccines and cure strategies

Conference Series LLC Joint International Event on 5^th European Immunology & Innate Immunity

July 21-23, 2016 Berlin, Germany

Zaza Ndhlovu, Thandeka Nkosi, Nikoshia Mewalal, Nasreen Ismail, Amber Moodley, Krista Dong, Thumbi Ndung u and Bruce D Walker

University of KwaZulu-Natal, South Africa
Ragon Institute of MGH, MIT and Harvard, USA
Howard Hughes Medical Institute, USA

Posters & Accepted Abstracts: J Clin Cell Immunol

Abstract :

Background: Early ART initiation is associated with substantial benefits such as reduced latently infected reservoir size and reduced mortality, but the impact of treatment initiation in hyperacute infection, before peak viremia, has not been determined. We investigated how antigen withdrawal through treatment of hyperacute infection affects phenotype, function and clonal repertoire of HIV-specific CD8+ T cell responses. Methods: 10 subjects who initiated ART in hyperacute infection (early treatment, ETx) and 12 subjects with untreated hyperacute HIV infection (UTx) were studied. We conducted a comparative longitudinal analysis of the phenotype, functionality and clonal repertoire of HIV-specific CD8+ T cell responses. MHC class I tetramers and ICS assays were used to characterize HIV specific responses. T cell receptors (TCRs) were sequenced from tetramer sorted and bulk CD8+ T cells. Results: Peak viral loads in ETx were 2 logs lower than UTx. Despite rapid antigen withdrawal, ETx led to detectable HIV specific CD8+ T cell responses with a distinct phenotypic profile, including heightened expression of interleukin-7 receptor alpha (CD127+) compared to untreated subjects (=0.0001). The majority of responses defined by HLA class-1 tetramers in ETx subjects persisted at relatively higher frequencies up to 12 months after initial detection of plasma HIV RNA. In contrast, >50% of the responses in untreated donors quickly became undetectable in the absence of discernible CTL driven escape mutations in the autologous plasma virus sequences. Furthermore, dominant TCR clonotypes of ETx subjects remained relatively stable over time compared to those from UTx donors. Conclusions: We show that very early ART is associated with HIV specific CD8+ T cell responses that are functionally distinct from UTx responses. Our data show that limiting antigen exposure in the hyperacute stage of infection results in more functionally competent immune responses with potential for long-term survival.