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Successful antiretroviral therapy is associated with increasing HCV-specific T cell responses
Janine Rohrbach1, Gillian Harcourt2, Silvana Gaudieri3, Nicola Robinson2, Amalio Telenti4, Matthias Egger5, Huldrych Günthard6, Paul Klenerman2, Hansjakob
Background: The impact of long-term antiretroviral therapy (ART) on HCV-specific T cell responses and on HCV viral loads is unclear.
Methods: HCV-specific CD4 T cell responses were assessed longitudinally in 80 HIV/HCV-coinfected individuals (58 with chronic and 22 with resolved HCV-infection) by ex vivo interferon-gamma ELISpot responses to HCV-core peptides, an assay previously demonstrated to measure CD4 T cell reactivity. HCV-RNA levels were assessed longitudinally by in-house real-time PCR in 62 individuals. Analyses were performed at the earliest available time-point after HIV-infection, just before starting ART and at three time-points after starting successful (HIV-viral loads < 1000 cp/ml during therapy) ART (time-points 1 to 5). All time-points were before starting anti-HCV therapy.
Results: Before starting ART, T-cell responses were detected in 2/16 individuals (13%) at time-point 1 and in 12/64 (19%) individuals at time-point 2. At time-point 3, 12/50 (24%) individuals had detectable HCV-responses. After a median of 33 and 74 months of successful ART, 29/64 (45%) and 18/37 (49%) individuals had HCV-specific T cell responses (p=0.002 and 0.003 compared to time-point 2). In 54 individuals with available PBMCs during both untreated and treated HIV-infection (time-points 2 and 4), the emergence of HCV-specific responses during successful ART was considerably more frequent than loss of detectable responses (31% vs 9%). HCV-specific responses on-therapy (time-point 4) were detected more frequently in the 58 individuals with resolved than in the 22 individuals with chronic HCV infection (61% vs 39%). Median HCV viral loads were 6.2 and 6.5 log10 IU/ml at time-points 1 and 2 (untreated HIV-infection) and 6.7, 6.3 and 6.2 log10 IU/ml at time-points 3, 4 and 5 (on-therapy).
Conclusion: A successful ART can increase HCV-specific T cell responses and is associated with a slight decrease in HCV RNA levels long-term. This finding supports consideration of earlier ART initiation in HIV/HCV-coinfected individuals.
Datei SOEDAK_09_OSE2.pdf