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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Soriano
Vincent
V
Hospital Carlos III, Madrid, Spain. vsoriano@dragonet.es
Miralles
Celia
C
Berdún
Miguel Angel
MA
Losada
Elena
E
Aguirrebengoa
Koldo
K
Ocampo
Antonio
A
Arazo
Piedad
P
Cervantes
Manuel
M
de los Santos
Ignacio
I
San Joaquín
Isabel
I
Echeverria
Santiago
S
Galindo
María J
MJ
Asensi
Victor
V
Barreiro
Pablo
P
Sola
Julio
J
Hernandez-Burruezo
Juan J
JJ
Guardiola
Josep
J
Blanco
Francisco
F
Martin-Carbonero
Luz
L
García-Samaniego
Javier
J
Nuñez
Marina
M
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a