Poor
Outcomes with Ribavirin Pre-treatment and Double-dose Pegylated Interferon in
HIV-HCV Coinfected Patients
 | Intensified
hepatitis C therapy using ribavirin pre-treatment followed by an induction regimen
of double dose of pegylated interferon did not lead to improved response rates
in hard-to-treat HIV-HCV coinfected patients, but serious adverse events and treatment
discontinuation were common, researchers reported at the 5th International AIDS
Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009) last
month in Cape Town, South Africa. |
By
Liz Highleyman Because
HIV-HCV coinfected individuals
do not respond as well to interferon-based
therapy as people with chronic hepatitis C alone,
researchers have studied various strategies for improving treatment response,
especially in difficult to treat patients. F.
Gatti and colleagues from Italy evaluated the safety and efficacy of a ribavirin
lead-in plus high-dose pegylated
interferon induction regimen to treat coinfected patients with HCV
genotypes 1 or 4 and advanced liver damage, both factors are linked to poor
treatment response. Between
January and September 2008, the pilot study enrolled participants with advanced
fibrosis or cirrhosis
diagnosed by means of transient elastometry (FibroScan; liver stiffness measurement
greater than 12 kPa) or liver biopsy (Metavir score of F3 or higher). A
total of 16 patients were treated according to the following schedule: Results  | Phase
1 (4 weeks): 14-17 mg/kg/day ribavirin lead-in. | | Phase
2 (12 weeks): double-dose 360 mcg/week pegylated interferon alfa-2a (Pegasys)
or 3 mcg/kg/week pegylated interferon alfa-2b (PegIntron) induction plus the same
dose of ribavirin. | | Phase
3 (36 weeks): standard-dose 180 mcg/week pegylated interferon alfa-2a or 1.5 mcg/kg/week
pegylated interferon alfa-2b, continuing on the same dose of ribavirin. |
Proportions
of patients achieving rapid virological response (RVR) after 4 weeks of combination
therapy, partial and complete early virological response (EVR) after 12 weeks,
and sustained virological response
(SVR) 24 weeks after completing treatment compared against corresponding response
rates achieved by 28 patients at the same center treated with standard pegylated
interferon plus ribavirin therapy for 48 weeks. Overall,
the 2 groups had similar baseline characteristics including sex ratio, age, body
mass index (BMI), HIV RNA and CD4 cell count, proportion with cirrhosis, and ribavirin
dose per weight. However, patients receiving standard therapy had a higher average
HCV RNA level and 8 people (vs none in the high-dose induction group) were taking
abacavir (Ziagen, also in the
Epzicom and Trizivir
coformulations), which in some prior studies has been linked to lower treatment
response rates.
Results | After
4 weeks, 3 of 16 patients (19%) in the high-dose induction group achieved RVR,
compared with 2 of 28 patients (7%) in the standard therapy group (odds ratio
[OR] 3; P = 0.2). | | After
12 weeks, 8 of 16 (50%) in the induction group and 15 of 28 (54%) in the standard
therapy group achieved partial EVR (OR 0.52; P = 0.3). | | 3
of 16 (19%) in the induction group and 3 of 28 (8%) in the standard therapy group
achieved complete EVR (OR 1.15; P = 0.4). | | Among
participants with adequate data 24 weeks after completing treatment, just 1 of
14 people (7%) in the induction arm and 2 of 27 (also 7%) in the standard therapy
arm achieved SVR (OR 1.04; P = 0.7). | | None
of these differences were statistically significant. | | 3
serious adverse events were reported in the induction group. | | All
16 patients in the induction group discontinued treatment early (13 due to poor
response and 3 due to adverse events), as did 22 in the standard therapy group
(16 due to poor response, 6 due to adverse events). |
In
this pilot trial, ribavirin pre-treatment and a pegylated interferon double-dose
induction regimen resulted in "disappointing short-term outcome" in
difficult-to- treat HIV-HCV coinfected patients, the investigators concluded.
They
added that, "New drugs or strategies are urgently needed to treat these patients."
Several
promising directly-targeted anti-HCV agents, including protease and polymerase
inhibitors, are in the development pipeline, but these have not yet been tested
in coinfected patients. University
of Brescia, Infectiuos and Tropical Diseases, Brescia, Italy 8/7/09 Reference
F
Gatti, P Nasta, G Cologni, and others. Ribavirin (RBV) pretreatment and double-dose
peg-interferon (peg-IFN) induction therapy in HIV-HCV coinfected patients with
advanced fibrosis/cirrhosis (AF/C) and HCV genotype 1-4: a single-center pilot
trial. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment,
and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract
WePeB223.
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