Virological response and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus coinfection.
OBJECTIVE
To evaluate virological response to telaprevir or boceprevir in combination with pegylated interferon and ribavirin and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients in a real life setting.


METHODS
Patients with HCV genotype 1-HIV coinfection followed in Nice University Hospital internal medicine and infectious diseases departments who initiated treatment including pegylated interferon and ribavirin (PegIFN/RBV) + telaprevir or boceprevir, according to standard treatment protocols, between August 2011 and October 2013 entered this observational study. Patient data were extracted from an electronic database (Nadis(®)). Liver fibrosis was measured by elastometry (Fibroscan(®)) with the following cut-off values: F0-F1: < 7.1 kPa, F2: 7.1-9.5 kPa, F3: 9.5-14.5 kPa, F4: ≥ 14.5 kPa. The proportion of patients with sustained virological response (SVR) twelve weeks after completing treatment, frequency and type of adverse events, and NS3/4A protease inhibitor mutations were described.


RESULTS
Forty-one patients were included: 13 (31.7%) patients were HCV-treatment naïve, 22 (53.7%) had advanced liver fibrosis or cirrhosis (Fibroscan stage F3 and F4); none had decompensated cirrhosis or hepatocellular carcinoma; all were receiving antiretroviral treatment, consisting for most them (83%) in either a nucleoside reverse-transcriptase inhibitor/protease inhibitor or/integrase inhibitor combination; all patients had undetectable HIV-RNA. One patient was lost to follow-up. SVR was achieved by 52.5% of patients. Five patients experienced virological failure during treatment and four relapsed. Seven discontinued treatment due to adverse events. Main adverse events included severe anemia (88%) and rash (25%). NS3/4A protease mutations were analyzed at baseline and at the time of virological failure in the 9 patients experiencing non-response, breakthrough or relapse. No baseline resistance mutation could predict resistance to HCV protease inhibitor-based treatment.


CONCLUSIONS
Telaprevir and boceprevir retain their place among potential treatment strategies in HIV-HCV coinfected patients including those with advanced compensated liver disease and who failed previous PegIFN/RBV therapy.
Alissa Naqvi, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Pierre Marie Roger, Infectious Diseases Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France.
Alissa
A
Naqvi
Alissa Naqvi, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Pierre Marie Roger, Infectious Diseases Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France.
Valérie
V
Giordanengo
Alissa Naqvi, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Pierre Marie Roger, Infectious Diseases Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France.
Brigitte
B
Dunais
Alissa Naqvi, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Pierre Marie Roger, Infectious Diseases Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France.
Francine
F
de Salvador-Guillouet
Alissa Naqvi, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Pierre Marie Roger, Infectious Diseases Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France.
Isabelle
I
Perbost
Alissa Naqvi, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Pierre Marie Roger, Infectious Diseases Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France.
Jacques
J
Durant
Alissa Naqvi, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Pierre Marie Roger, Infectious Diseases Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France.
Pascal
P
Pugliese
Alissa Naqvi, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Pierre Marie Roger, Infectious Diseases Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France.
Aline
A
Joulié
Alissa Naqvi, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Pierre Marie Roger, Infectious Diseases Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France.
Pierre Marie
PM
Roger
Alissa Naqvi, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Pierre Marie Roger, Infectious Diseases Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France.
Eric
E
Rosenthal
Boceprevir; Hepatitis C virus-human immunodeficiency virus coinfection; Resistance mutations; Telaprevir