This prospective, multicenter, open-label
trial included 389 interferon-naive HIV-HCV coinfected patients with CD4 counts
above 300 cells/mm3 and elevated aminotransferase (ALT and AST) levels. Patients
were not taking AZT (Retrovir)
or ddI (Videx). About two-thirds
(61%) had HCV genotypes 1 or 4; most of the remainder had genotype 3, and genotype
2 was uncommon. HCV RNA levels were greater than 500,000 IU/ml in 67% of subjects.
The
researchers hypothesized that poor therapeutic response in coinfected patients
compared with HCV monoinfected individuals in prior studies might have been due
to the use of low flat doses of ribavirin (800 mg/day) or short durations of therapy.
Therefore, all PRESCO participants received 180 mcg/week pegylated interferon
alfa-2a (Pegasys) plus weight-based ribavirin (1000 mg daily if body weight was
less than 75 kg; 1200 mg daily if heavier). Patients with HCV genotypes 1 and
4 were treated for either 48 (n = 192) or 72 weeks (n = 45), while patients with
HCV genotypes 2 and 3 were treated for either 24 (n = 96) or 48 weeks (n = 56). Results
In an intent-to-treat analysis, 49.6% of patients overall achieved SVR: - 72.4%
in those with genotypes 2 or 3; - 35.6% in those with genotype 1. - 32.6%
in those with genotype 4.
Post-treatment relapse occurred in 35% of genotype 1 patients and 20% with genotype
4 (only a few relapsers had genotypes 2 or 3).
SVR rates were higher among patients assigned to received extended vs standard
durations of therapy: - Genotypes 1 or 4: 53% with 72 weeks vs 31% with 48
weeks; - Genotypes 2 or 3: 82% with 48 weeks vs 67% with 24 weeks;
The drop-out rate was high in the extended duration arms.
The overall discontinuation rate was 34.6%.
Premature treatment due to serious adverse events occurred in 8.2% of patients
overall.
15%-20% had pegylated interferon or ribavirin doses reduced due to adverse events.
In a multivariate analysis, factors that independently predicted SVR were: -
infection with genotype 2 or 3 HCV; - lower baseline HCV viral load; - HCV
RNA < 50 IU/ml at Week 12 (early virological response).
Conclusion
"The use of 1000-1200 mg/day of ribavirin was relatively safe
and provided SVR in nearly half of HCV-HIV coinfected patients," the researchers
concluded, with rates twice as high in those with genotypes 2 or 3 compared with
genotypes 1 or 4.
The
SVR rates in PRESCO were higher than those observed in past trials, for example
the pivotal APRICOT
trial (which used fixed-dose 800 mg ribavirin), reported in 2004*:
According
to the PRESCO researchers, "Both the use of higher ribavirin doses and extended
duration of therapy most likely explained the better responses in this study compared
to prior trials conducted in coinfected patients."
12/01/06
References
M
Nunez, C Miralles, M A Berdun, and others. The PRESCO trial: role of extended
duration of therapy with pegylated interferon alfa-2a plus weight-based ribavirin
dose in 389 HCV/HIV co-infected patients. 8th Congress on Drug Therapy in HIV
Infection (HIV8). Glasgow. November 12-16, 2006. Abstract PL13.1.
*F
J Torriani and others (for the APRICOT Study Group). Peginterferon Alfa-2a plus
Ribavirin for Chronic Hepatitis C Virus Infection in HIV-infected Patients.
The New England Journal of Medicine 351(5): 438-450. July 29, 2004.
In an intent-to-treat analysis, 49.6% of patients overall achieved SVR: