Boceprevir plus pegylated interferon/ribavirin to re-treat hepatitis C virus genotype 1 in HIV-HCV co-infected patients: final results of the Spanish BOC HIV-HCV Study.
BACKGROUND
Boceprevir (BOC) was one of the first oral inhibitors of hepatitis C virus (HCV) NS3 protease to be developed. This study assessed the safety and efficacy of BOC+pegylated interferon-α2a/ribavirin (PEG-IFN/RBV) in the retreatment of HIV-HCV co-infected patients with HCV genotype 1.


METHODS
This was a phase III prospective trial. HIV-HCV (genotype 1) co-infected patients from 16 hospitals in Spain were included. These patients received 4 weeks of PEG-IFN/RBV (lead-in), followed by response-guided therapy with PEG-IFN/RBV plus BOC (a fixed 44 weeks was indicated in the case of cirrhosis). The primary endpoint was the sustained virological response (SVR) rate at 24 weeks post-treatment. Efficacy and safety were evaluated in all patients who received at least one dose of the study drug.


RESULTS
From June 2013 to April 2014, 102 patients were enrolled, 98 of whom received at least one treatment dose. Seventy-three percent were male, 34% were cirrhotic, 23% had IL28b CC, 65% had genotype 1a, and 41% were previous null responders. The overall SVR rate was 67%. Previous null-responders and cirrhotic patients had lower SVR rates (57% and 51%, respectively). Seventy-six patients (78%) completed the therapy scheme; the most common reasons for discontinuation were lack of response at week 12 (12 patients) and adverse events (six patients).


CONCLUSIONS
Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC+PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferon-free therapies are not available yet.
Hospital Clínic de Barcelona/IDIBAPS, Villarroel 170, Barcelona, Spain.
M
M
Laguno
Hospital Universitario de Donostia, Donostia, Spain.
M A
MA
Von Wichmann
Hospital Universitari de Bellvitge, Bellvitge, Spain.
E
E
Van den Eynde
Hosital Universitari Vall d'Hebrón, Barcelona, Spain.
J
J
Navarro
Hospital Son Llàtzer, Palma de Mallorca, Spain.
C
C
Cifuentes
Hospital Son Espases, Palma de Mallorca, Spain.
J
J
Murillas
Hospital Universitari Joan XXIII, Tarragona, Spain.
S
S
Veloso
Hospital Clínic de Barcelona/IDIBAPS, Villarroel 170, Barcelona, Spain. Electronic address: rebollar@clinic.cat.
M
M
Martínez-Rebollar
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
J M
JM
Guardiola
Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
A
A
Jou
Hospital Universitario de Canarias, Tenerife, Spain.
J L
JL
Gómez-Sirvent
Corporació Sanitària Parc Taulí, Sabadell, Spain.
M
M
Cervantes
Hospital Universitario de Valme, Seville, Spain.
J A
JA
Pineda
Hospital Universitario A Coruña, La Coruña, Spain.
S
S
López-Calvo
Hospital Universitario Gregorio Marañón, Madrid, Spain.
A
A
Carrero
Hospital Universitario de La Paz, Madrid, Spain.
M L
ML
Montes
Hospital de Granollers, Granollers, Spain.
E
E
Deig
Fundació Althaia, Manresa, Spain.
A
A
Tapiz
Hospital Regional, Malaga, Spain.
J D
JD
Ruiz-Mesa
Hospital Clínic de Barcelona/IDIBAPS, Villarroel 170, Barcelona, Spain.
A
A
Cruceta
Hospital Clínic de Barcelona/IDIBAPS, Villarroel 170, Barcelona, Spain.
E
E
de Lazzari
Hospital Clínic de Barcelona/IDIBAPS, Villarroel 170, Barcelona, Spain.
J
J
Mallolas
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D060085:Coinfection; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D019233:Retreatment; D012254:Ribavirin / Q000627:therapeutic use; D013030:Spain; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011392:Proline; D011994:Recombinant Proteins; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; C100416:peginterferon alfa-2a
HCV genotype 1; HIV–HCV experienced patients; PEG-IFN/RBV+BOC therapy; Re-treatment