HIV reservoir size and composition, after antiretroviral treatment initiation, is related to HIV-specific CD8+ T-cell responses developed during primary HIV infection

YANINA GHIGLIONE; AJANTHA SOLOMON; HORACIO SALOMÓN; SHARON R. LEWIN; JIMENA SALIDO; MARÍA LAURA POLO; OMAR SUED; CÉSAR TRIFONE; MARÍA JULIA RUIZ; NATALIA LAUFER; GABRIELA TURK

Paris

Conferencia; 9th IAS Conference on HIV Science; 2017

International AIDS Society

Background:The persistence of latently infected T-cells remains the major obstacle to cure HIV. Understanding the early events that occur after infection and establish HIV latency will be fundamental for potential eradication. We aimed to determine the relationship between CD8+ cytotoxic T lymphocyte (CTL) function and HIV persistence on antiretroviral therapy (ART). Methods:Twenty-one individuals were enrolled during acute/early HIV infection (median 2 month post-infection, mpi) and started ART within 12 mpi. Blood samples were obtained at enrollment (baseline sample, pre-ART) and every 3 months (on-ART) during 2 years. Cell-associated HIV DNA and unspliced (US) RNA were quantitated by real-time PCR, in samples on-ART. HIV-specific CTLs were identified based on cytokines/CD107 production upon peptide stimulation. Phenotypic (CD45RO, CCR7, PD-1) markers were studied in baseline samples on bulk and HIV-specific CTLs by flow cytometry. Data was analyzed using non-parametric statistics.Results:HIV DNA and US RNA rapidly diminished after ART initiation, reaching a plateau by 30 weeks post-ART (median total HIV DNA 159 copies/106 cell equivalents; unspliced (US)-RNA 14 copies/106 18S copies). HIV-specific CTLs profile at baseline was: 52% terminal effectors (TTE); 20% naïve-like; 13% effector memory (TEM) and 5% central memory. PD-1+ HIV-specific CTLs were 24.7%. Also, high intensity PD-1 (PD-1High) expression was measured in 1.2% CTLs.Spearman?s correlations showed that the proportion of baseline naïve CTLs was inversely correlated with levels of cell-associated US-RNA measured at 12 month post-ART (mp-ART) (r=-0.6321, p=0.005). A higher proportion of bulk and HIV-specific CD8+ TEM cells at baseline correlated with higher levels of US-RNA measured at 12 mp-ART (r=0.6746, p=0.002 and r=0.5752, p=0.017; respectively). The percentage of HIV-specific CD8+ TTE cells positively correlated with total HIV DNA levels at 12 mp-ART (r=0.6888, p=0.011). Finally, a strong positive correlation was observed between the proportion of bulk and HIV-specific PD-1high CTLs measured at baseline and total HIV DNA levels at 12 mp-ART (r=0.5005, p=0.034 and r=0.7349, p=0.006; respectively).Conclusion:Results suggest that higher proportion of terminally differentiated CTLs and higher CTL exhaustion are related to higher HIV reservoir size. Thus, the quality of early CTL immune responses may serve as a predictor of HIV persistence on ART.