905
Causes of Premature Discontinuation in HIV/HCV Co-infected Patients in PRESCO, a Large Trial of Treatment with Pegylated Interferon plus Weight-based Ribavirin
Vincent Soriano*1, E Losada2, I San Joaquin3, J Guardiola4, I Santos5, J Portu6, L Bonet7, C Miralles8, P Barreiro1, M Nunez1, and on behalf of PRESCO Study Group
1Hosp Carlos III, Madrid, Spain; 2Hosp Clin Univ, Santiago; 3Hosp Clin, Zaragoza; 4Hosp de St Pau, Barcelona, Spain; 5Hosp de la Princesa, Madrid, Spain; 6Hosp Txagorritxu, Vitoria; 7Hosp Son Dureta, Mallorca; and 8Hosp Xeral-Cies, Vigo, Spain
Background: The treatment of chronic hepatitis C virus (HCV) in HIV+
patients is often penalized by more frequent premature discontinuations. It is
unclear the relative contribution of more frequent adverse events and/or early virological failure.
Methods: PRESCO was a prospective, multicenter,
open, comparative trial, in which 389 HCV/HIV-co-infected patients with CD4
counts >300 cells/mL
and elevated aminotransferases received pegylated interferon-α-2a (180 mg/week) plus ribavirin (1000 mg
daily if body weight <75 kg; 1200 mg daily if >75 kg). Patients with HCV
genotypes 1 and 4 (61%) were treated for 48 or 72 weeks, while those with HCV
genotypes 2 and 3 (39%) were treated for 24 or 48 weeks. Use of didanosine (ddI) was not allowed.
Results: Sustained
virological response was achieved by 193 (49.6%) of
patients, significantly greater in HCV-2/3 than in HCV-1/4 patients (72.4% vs 35%, p
<0.0001). Overall, premature treatment discontinuations occurred in 174
(45%) of patients. It was due to early virological
failure in 66 (17%), to serious adverse events in 32 (8.2%), to
lost-to-follow-up in 12 (3.1%) and to voluntary withdrawal in 64 (16.5%). The
latest occurred mainly in G1/4 patients ascribed to the extended treatment arm.
Only 9 patients (2.4%) stopped HCV therapy due to severe anemia; however, only
21.8% of patients in PRESCO received zidovudine (AZT) compared with 28% in RIBAVIC and 40% in APRICOT. Of note, only 6 patients in
PRESCO received erythropoietin. HCV medication for 2 patients was stopped because of symptomatic
mitochondrial toxicity (lactic acidosis and pancreatitis,
respectively). There were no episodes of hepatic decompensation,
and only 1 death (a patient who committed suicide).
Conclusions: The use of 1000 to 1200 mg/day of ribavirin
(RBV) along with pegIFN-α-2a 180 mg
per week is relatively safe and provides sustained virological
response in nearly half of HCV/HIV-co-infected patients, twice greater in
HCV-2/3 than HCV-1/4 carriers. Avoidance of ddI,
limited use of AZT and restriction of therapy to patients with CD4 counts
>300 cells/mL
most likely explain
the lower and different spectrum of serious adverse events in PRESCO compared
to prior trials conducted in HIV/HCV-co-infected patients.
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