Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy.
BACKGROUND
Hepatitis C virus (HCV) infection is a major cause of morbidity in HIV infected individuals. Coinfection with HIV is associated with diminished HCV-specific immune responses and higher HCV RNA levels.


OBJECTIVE
To investigate whether long-term combination antiretroviral therapy (cART) restores HCV-specific T cell responses and improves the control of HCV replication.


METHODS
T cell responses were evaluated longitudinally in 80 HIV/HCV coinfected individuals by ex vivo interferon-gamma-ELISpot responses to HCV core peptides, that predominantly stimulate CD4(+) T cells. HCV RNA levels were assessed by real-time PCR in 114 individuals.


RESULTS
The proportion of individuals with detectable T cell responses to HCV core peptides was 19% before starting cART, 24% in the first year on cART and increased significantly to 45% and 49% after 33 and 70 months on cART (p=0.001). HCV-specific immune responses increased in individuals with chronic (+31%) and spontaneously cleared HCV infection (+30%). Median HCV RNA levels before starting cART were 6.5 log(10) IU/ml. During long-term cART, median HCV-RNA levels slightly decreased compared to pre-cART levels (-0.3 log10 IU/ml, p=0.02).


CONCLUSIONS
Successful cART is associated with increasing cellular immune responses to HCV core peptides and with a slight long-term decrease in HCV RNA levels. These findings are in line with the favourable clinical effects of cART on the natural history of hepatitis C and with the current recommendation to start cART earlier in HCV/HIV coinfected individuals.
Rohrbach
Janine
J
Klinik und Poliklinik für Infektiologie, University Hospital Berne and University of Berne, Inselspital PKT2B, 3010 Bern, Switzerland.
Robinson
Nicola
N
Harcourt
Gillian
G
Hammond
Emma
E
Gaudieri
Silvana
S
Gorgievski
Meri
M
Telenti
Amalio
A
Keiser
Olivia
O
Günthard
Huldrych F
HF
Hirschel
Bernhard
B
Hoffmann
Matthias
M
Bernasconi
Enos
E
Battegay
Manuel
M
Furrer
Hansjakob
H
Klenerman
Paul
P
Rauch
Andri
A
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D018936:Hepatitis C Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D008137:Longitudinal Studies; D008297:Male; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology; D019562:Viral Load / Q000187:drug effects
D019380:Anti-HIV Agents; D018936:Hepatitis C Antigens; D012367:RNA, Viral; D014758:Viral Core Proteins; D007371:Interferon-gamma