HIV
and Hepatitis.com Coverage of the 14th
Annual Conference on Retroviruses and Opportunistic Infections (14th CROI) February
25 - 28, 2007, Los Angeles, CA
Three Studies Examine Hepatitis C Treatment in HIV-HCV Coinfected Patients
Patients with genotypes 1 or 4 HCV received treatment for either
the standard duration of 48 weeks or an extended duration of 72 weeks; those with
genotype 2 or 3 were treated for either the standard 24 weeks or an extended 48
weeks. Participants discontinued therapy if they did not achieve at least a 2
log decrease in HCV RNA by week 12. Results
•
There was a high drop-out rate (63%), mainly due to voluntary
withdrawal, in the extended duration arms.
•
In
a multivariate analysis, a baseline HCV
RNA level above 500,000 IU/mL and continued detectable HCV RNA at week 4 predicted
relapse.
•
Extended treatment did not lower the relapse rate regardless
of genotype.
•
Among patients with detectable HCV RNA at weeks 4 or 12,
relapse rates were comparable in the standard and extended duration arms.
"Higher
baseline HCV RNA levels and detectable HCV RNA at week 4 of therapy were predictors
of relapse following a course of [pegylated
interferon + ribavirin] in HIV-HCV coinfected patients," the researchers
concluded. "No benefit was seen with extended treatment durations, regardless
of HCV genotype."
Hosp Carlos III, Madrid, Spain; Hosp Arquitecto
Marcide, Ferrol, Spain; Hosp Xeral-Cies, Vigo, Spain; Hosp San Jorge, Huesca,
Spain; Hosp de Navarra, Pamplona, Spain; Hosp Gen, Jaen, Spain; Hosp Clin, Valencia,
Spain.
In
another presentation from PRESCO, Vincent Soriano and colleagues reported on causes
of treatment discontinuation.
Results
•
Overall,
45% of patients discontinued treatment prematurely, for the following reasons:
-
virological failure: 17%; - serious adverse events 8.2%; - lost to follow-up:
3.1%; - voluntary withdrawal: 16.5%.
•
Voluntary
withdrawal was most common among genotype 1 or 4 patients assigned to the 72-week
arm.
•
Only
9 patients (2.4%) stopped therapy due to severe anemia.
•
2
stopped therapy due to symptomatic mitochondrial toxicity (lactic acidosis, pancreatitis).
"Avoidance
of ddI, limited use of AZT, and restriction of therapy to patients with CD4 counts
> 300 [cells/mm3] most likely explain the lower and different spectrum of serious
adverse events in PRESCO compared to prior trials conducted in HIV-HCV coinfected
patients," the investigators concluded.
Discussing the low rate of
anemia in this study, the researchers noted that only about 22% of patients in
PRESCO were taking AZT (Retrovir), which can also cause this toxicity. This compares
with 28% in the French RIBAVIC trial and 40% in the APRICOT
trial, both of which found lower SVR rates. Similarly, ribavirin and ddI (Videx)
can both cause mitochondrial toxicity, increasing the risk of adverse events when
the 2 drugs are used together.
Hosp Carlos III, Madrid, Spain; Hosp
Clin Univ, Santiago; Hosp Clin, Zaragoza; Hosp de St Pau, Barcelona, Spain; Hosp
de la Princesa, Madrid, Spain; Hosp Txagorritxu, Vitoria; Hosp Son Dureta, Mallorca;
Hosp Xeral-Cies, Vigo, Spain
•
In
an intent-to-treat analysis, mean HCV RNA decay was similar in patients receiving
Pegasys and PegIntron (2.6 log IU/mL at week 4; about 4.0 log IU/mL at week 12;
about 4.4 log IU/mL at week 24).
•
Rates of virological response were also comparable for
Pegasys and PegIntron:
- rapid virological response at 4 weeks: 25% and
23%, respectively (17% and 16% for genotype 1); - early virological response
at 12 weeks: 85% and 86% (78% and 82% for genotype 1); - undetectable HCV
RNA at week 24: 81% and 76% (77% and 69% for genotype 1).
•
The ribavirin plasma concentration at week 12 that best
predicted undetectable HCV RNA at week 24 was 2.1 mcg/mL.
"The
intrinsic antiviral activity of [pegylated interferon alpha-2a and alpha-2b] seems
to be comparable in HCV-HIV coinfected patients during the first 24 weeks of therapy,"
the researchers concluded. "The attainment of high ribavirin plasma concentrations,
rather than the [pegylated interferon] modality, is the main determinant for virological
success of anti-HCV therapy.
M
Nunez, A Marino, C Miralles, and others. Extended Treatment Does Not Reduce Relapses
in HIV/HCV-co-infected Patients Treated with Pegylated Interferon + Weight-dosing
Ribavirin. 14th Conference on Retroviruses and Opportunistic Infections (CROI).
Los Angeles, February 25-28, 2007. Abstract 899 (poster).
V
Soriano, E Losada, I San Joaquin, and others (PRESCO Study Group). Causes of Premature
Discontinuation in HIV/HCV Co-infected Patients in PRESCO, a Large Trial of Treatment
with Pegylated Interferon plus Weight-based Ribavirin. 14th CROI. Abstract 905
(poster).
P Barreiro, S Rodríguez-Novoa, P Labarga, and others.
Comparison of Hepatitis C Virus Early Kinetics in HIV/HCV-co-infected Patients
Treated with Weight-based Ribavirin + Either PegIFN alpha-2a or PegIFN alpha-2b.
14th CROI. Abstract 901 (poster).
