Premature treatment discontinuation in HIV/HCV-coinfected patients receiving pegylated interferon plus weight-based ribavirin

• Published in: Antiviral therapy Vol. 12; no. 4; pp. 469 - 476
• Main Authors: SORIANO, Vincent, MIRALLES, Celia, ECHEVERRIA, Santiago, GALINDO, Maria J, ASENSI, Victor, BARREIRO, Pablo, SOLA, Julio, HERNANDEZ-BURRUEZO, Juan J, GUARDIOLA, Josep, BLANCO, Francisco, MARTIN-CARBONERO, Luz, GARCIA-SAMANIEGO, Javier, BERDUN, Miguel Angel, NUNEZ, Marina, LOSADA, Elena, AGUIRREBENGOA, Koldo, OCAMPO, Antonio, ARAZO, Piedad, CERVANTES, Manuel, DE LOS SANTOS, Ignacio, SAN JOAQUIN, Isabel
• Format: Journal Article
• Language: English
• Published: London International Medical Press 01-01-2007
• Subjects: Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Biological and medical sciences; Drug Administration Schedule; Drug Therapy, Combination; Female; Hepacivirus - drug effects; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; HIV Infections - complications; HIV Infections - drug therapy; HIV-1 - drug effects; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; Interferon-alpha - therapeutic use; Male; Medical sciences; Pharmacology. Drug treatments; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - adverse effects; Polyethylene Glycols - therapeutic use; Recombinant Proteins; Ribavirin - administration & dosage; Ribavirin - adverse effects; Ribavirin - therapeutic use; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Human; Premature; Immunopathology; Drug combination; Mixed infection; Cytokine; AIDS; Immune deficiency; Ribavirin; Infection; Virus; Treatment; Viral disease; Nucleoside analog; Antiviral; Interferon; Flaviviridae; Pegylated form; Hepatitis C virus; Hepacivirus
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350701200402

Chronic hepatitis C therapy in HIV patients is often penalized by more frequent premature treatment discontinuations. It is unclear what the relative contribution of more adverse events and/or early virological failures are.
PRESCO was a prospective, multicentre, comparative trial, in which 389 HIV/HCV-coinfected patients with CD4+ T-cell counts >300 cells/ml and elevated aminotransferases received pegylated interferon-alpha2a (peg IFN-alpha2a) 180 mg per week plus ribavirin (RBV) 1,000-1,200 mg daily. Patients with HCV genotypes 1 or 4 were treated for 48 or 72 weeks while HCV genotypes 2 or 3 carriers were treated for 24 or 48 weeks. Use of didanosine was not allowed.
Sustained virological response (SVR) was achieved by 193 (49.6%), and was significantly greater in HCV-2/3 than in HCV-1/4 patients (72.4% versus 35%; P<0.0001). Premature treatment discontinuations occurred in 174 patients (44.7%). This was due to early virological failure in 66 (17%), serious adverse events in 32 (8.2%), loss-to-follow-up in 12 (3.1%) and voluntary withdrawal in 64 (16.4%). Only 10 patients (2.6%) stopped HCV therapy due to severe anaemia. Two patients stopped HCV medication due to symptomatic mitochondrial toxicity. There were no episodes of hepatic decompensation.
Treatment with RBV 1,000-1,200 mg/day plus peg IFN-alpha2a is relatively safe and provided SVR in nearly half of the HIV/HCV-coinfected patients, twice as many amongst the HCV-2/3 than HCV-1/4 carriers. Avoidance of didanosine, limited use of zidovudine and therapy restricted to patients with CD4+ T-cell counts >300 cells/ml most probably explains the lower and different spectrum of serious adverse events in PRESCO compared with prior trials conducted in coinfected patients.