Transcriptional analysis of HIV-specific CD4+ T cells after suppression of viremia by ART.

The virus-specific CD4+ T cell dysfunction associated with failure to control chronic infections is poorly understood in humans. An issue of critical clinical relevance is the lack of restoration of effective anti-HIV immunity after suppressive ART: viral rebound is the rule after cessation of therapy. Whether persistent HIV-specific CD4+ T cell dysfunction on ART contribute to this failed response is an important, yet unresolved, question. To decipher the consequences of ongoing viral antigen exposure, versus the results of durable cell-fate decision programs that would persist in former CP individuals after successful viral suppression on ART, we compared trancriptional profiles of chronic progressor before and after the initiation of ART, with the transcriptional profiles of elite controllers, HIV-infected individuals that spontaneously control viral load. Suppression of viremia by ART resulted in a distinct transcriptional landscape, with reduction in TFH gene expression but no correction of the TH1, TH17 and TH22 gene levels compared to the elite controller profile. HIV-specific CD4 T cells were live-sorted after a 9-h stimulation of PBMCs with an HIV Gag peptide pool based on coupregulation of activation markers CD40L and CD69. The HIV-infected individuals were categorized in 3 groups: “Chronic progressors before ART (CPpre) (n=8), untreated HIV-infected individuals with a viral load of more than 5,000 vRNA copies per ml of plasma; Chronic progressors after ART (CPpost) (n=8), longitudinally followed CPs for at least 6 months after initiation of ART therapy and suppression of viral load below 50 copies mL ; and elite controllers (EC) (n=12), HIV-infected individuals who spontaneously controlled viremia to below 50 RNA copies per ml plasma in the absence of therapy.