T-Cell Exhaustion in HIV-1/Hepatitis C Virus Coinfection Is Reduced After Successful Treatment of Chronic Hepatitis C.

BACKGROUND

T-cell responses during chronic viral infections become exhausted, which is reflected by upregulation of inhibitory receptors (iRs) and increased interleukin 10 (IL-10). We assessed 2 iRs-PD-1 (programmed cell death protein 1) and Tim-3 (T-cell immunoglobulin and mucin domain-containing protein 3)-and IL-10 mRNAs in peripheral blood mononuclear cells (PBMCs) and their soluble analogs (sPD-1, sTim-3, and IL-10) in plasma in chronic HIV-1/hepatitis C virus (HCV) coinfection and explored the effect of HCV treatment on these markers. We also aimed to establish whether iR expression may be determined by the HCV CD8 T-cell immunodominant epitope sequence.

METHODS

Plasma and PBMCs from 31 persons with chronic HIV-1/HCV coinfection from the Swiss HIV Cohort Study were collected before and after HCV treatment. As controls, 45 persons who were HIV-1 negative with chronic HCV infection were recruited. Exhaustion markers were assessed by enzyme-linked immunosorbent assay in plasma and by quantitative reverse transcription polymerase chain reaction in PBMCs. Analysis of an HCV epitope sequence was conducted by next-generation sequencing: HLA-A02-restricted NS3 and NS3 and HLA-A01-restricted NS3.

RESULTS

The study revealed higher plasma sPD-1 ( = .0235) and IL-10 ( = .002) levels and higher IL-10 mRNA in PBMCs ( = .0149) in HIV-1/HCV coinfection. A decrease in plasma sPD-1 ( = .0006), sTim-3 ( = .0136), and IL-10 ( = .0003) and Tim-3 mRNA in PBMCs ( = .0210) was observed following successful HCV treatment. Infection with the HLA-A*01-restricted NS3 ATDALMTGY prototype variant was related to higher sTim-3 levels than infection with the ATDALMTGF escape variant ( = .0326).

CONCLUSIONS

The results underscore the synergistic effect of coinfection on expression of exhaustion markers, their reduction following successful HCV treatment and imply that iR levels may operate on an epitope-specific manner.