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.
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
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.