Acute hepatitis C in HIV-infected patients: rare spontaneous clearance correlates with weak memory CD4 T-cell responses to hepatitis C virus.
OBJECTIVE
To explore the parameters of specific immunity to hepatitis C virus (HCV) associated with virus clearance during acute HCV infection in HIV coinfection.


METHODS
HIV-infected patients without prior HCV infection were prospectively enrolled for acute hepatitis C and followed up over 15 months. HCV-specific T cells were assessed by proliferation, ELISpot, intracellular cytokine staining and pentamer assays. Pegylated-interferon-alpha and ribavirin were proposed if HCV persisted at M3.


RESULTS
Thirty eight acutely HCV-infected HIV-positive patients were enrolled. HCV genotypes were predominantly 4 and 1. Five patients (13%) showed spontaneous clearance and 20 initiated treatment, of whom 13 (65%) showed sustained virologic responses. Before M3, HCV-specific proliferative responses observed in 35% cases, were associated with lower HCV viral load (P = 0.04) and predictive of spontaneous clearance (P = 0.02), particularly anti-NS4 responses (P = 0.03). These HCV-specific proliferative responses were associated with HIV-p24-specific responses (P = 0.002) independently from the HIV stage. Interferon-gamma-producing T cells specific for HCV were detectable ex vivo in 81% cases but at low intensity (<150 spot forming cells/10 peripheral blood mononuclear cells) and were independent of the HCV outcome. Low frequencies of pentamer-positive HCV-specific CD8 cells (0.01-0.05%) detected in nine of 12 patients were mainly effector-memory PD-1-negative T cells. Twelve days of HCV-specific in-vitro culture induced amplification of CD4 T cells coproducing interleukin-2 and interferon-gamma but rarely of CD8 T cells.


CONCLUSIONS
Acute HCV infection in HIV-coinfected patients is characterized by a low rate of spontaneous clearance and weak HCV-specific memory T cells, not strictly related to HIV-induced immune defects, and which correlate with virus clearance.
Schnuriger
Aurélie
A
INSERM, UMRS-945, Paris, France.
Dominguez
Stéphanie
S
Guiguet
Marguerite
M
Harfouch
Sawsan
S
Samri
Assia
A
Ouazene
Zineb
Z
Slama
Laurence
L
Simon
Anne
A
Valantin
Marc-Antoine
MA
Thibault
Vincent
V
Autran
Brigitte
B
D000208:Acute Disease; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral; D012075:Remission, Spontaneous; D019562:Viral Load
D012367:RNA, Viral