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Factors Associated with Virological Non-response to Peg-Interferon + Ribavirin Therapy in HIV/HCV-Co-infected Patients: The Role of Abacavir
Firouzé Bani-Sadr*1, L Denoeud1, P Morand2, F Lunel-Fabiani3, S Pol4, P Cacoub5, C Perronne6, F Carrat1, and and the ANRS HC02 – Ribavic Study team
1Groupe Hosp Univ Est, Univ Paris 6, INSERM U707, France; 2Ctr Hosp Univ Grenoble, France; 3Ctr Hosp Univ Angers, France; 4Groupe Hosp Univ Ouest, Univ Paris 5, INSERM U568, France; 5Groupe Hosp Univ Est, Univ Paris 6, France; and 6Ctr Hosp Univ Raymond Poincare, Univ de Versailles, Garches
Background: Co-infection with HIV increases the rate of
patients who show HCV RNA declines of <2 log at 12 weeks during optimal
interferon (INF) + ribavirin (RBV) -based therapy.
Methods: This study determines baseline host factors,
HIV and HCV factors associated with non-response to pegylated INFα-2b (1.5
µg/kg weekly) + RBV (800 mg daily) among HIV/HCV-co-infected patients.
Results: Among 154 patients who had taken at least 80%
of the total dose regimen during the first 12 weeks, 57 (37%) patients failed
to achieve an early virological response: 10.3 % in patients with genotype 2 or
3 and 53.1% in patients with genotype 1 or 4. In multivariate analysis, HCV
viral load (OR 2.11, 95%CI, 1.11 to 4.0, p
= 0.022), genotype 1 or 4 (OR 12.13, 95%CI 4.27 to 34.47, p <0.0001), abacavir (ABC) -based ART (OR 4.92, 95%CI 1.50 to 16.06,
p = 0.0083) and baseline bilirubin
level (OR 4.52, 95%CI 1.53 to 13.36, p
= 0.0064) were significantly associated with the risk of non-response. The
following factors were not associated with the risk of non-response: age, sex, mean duration of HIV and HCV
infection, AIDS status, baseline CD4 cell count, HIV viral load <400
copies/mL, ongoing ART, the mean duration of previous ART, the mean daily RBV dose, the mean METAVIR
scores for necroinflammation and fibrosis, cirrhosis, the presence of steatosis,
prothrombin time, and alanine
aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, and alkaline phosphatase
levels. In patients infected with genotype 1 or 4, ABC-based ART (OR 4.15, 95%CI 1.14
to 15.13, p = 0.031) and baseline
bilirubin (OR 5.2, 95%CI 1.34 to 20.36, p
= 0.017) level remained significantly associated with the risk of non
response in multivariate analysis.
Conclusions: The potential negative interaction between RBV
and ABC on the HCV viral response highlights the need to understand the
pharmacological mechanisms underlying these events to enable the safe use of
this combined viral therapy.
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