Impact of HIV on host-virus interactions during early hepatitis C virus infection.
BACKGROUND
Human immunodeficiency virus (HIV) may influence the outcome and natural history of hepatitis C virus (HCV) infection through an impact on acute HCV-specific T cell responses.


METHODS
Fifty-five HIV-positive males with acute HCV infection were identified; monoinfected individuals (n = 8) were used for peripheral blood mononuclear cell comparison. In 14 coinfected and 8 HCV-monoinfected patients, HCV-specific T cell responses against a range of HCV antigens were assessed using interferon (IFN)-gamma enzyme-linked immunospot (ELISpot) and proliferation assays. E1/E2 region genetic diversity and the selection pressure on the virus were measured in 8 coinfected patients by use of cloned sequences over time.


RESULTS
HCV persisted in 52 (95%) coinfected individuals. HCV/HIV coinfection significantly reduced IFN-gamma ELISpot responses versus those in HCV-monoinfected individuals, especially against nonstructural proteins (1/10 vs. 5/8; P = .008). In coinfected patients, increased HCV genetic diversity was observed between the first and subsequent time points, with no evidence for positive selection in the E1/E2 region sequenced.


CONCLUSIONS
HIV coinfection is associated with increased rates of HCV persistence and a lack of critical CD4 T cell responses, with no evidence of immune selection pressure during early HCV infection. Loss of key cellular immune responses against HCV during acute disease may contribute to the failure of early host control of HCV in HCV/HIV-coinfected patients.
Danta
M
M
Centre for Hepatology, Royal Free and University College Medical School, London. m.danta@unsw.edu.au
Semmo
N
N
Fabris
P
P
Brown
D
D
Pybus
O G
OG
Sabin
C A
CA
Bhagani
S
S
Emery
V C
VC
Dusheiko
G M
GM
Klenerman
P
P
D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics
D000956:Antigens, Viral; C087035:E1 protein, Hepatitis C virus; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D007371:Interferon-gamma