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  International AIDS Conference
July 13-16, 2003, Paris
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Viral Response to Peginterferon plus Ribavirin in Co-infection
Reported by Jules Levin
  These two studies of peginterferon plus ribavirin in co-infected patients were reported at the IAS Conference. The data presented is not complete as adherence and adverse events data are incomplete. But viral response rates are presented.
E Voigt1, C Schulz1, S Mauss2, G Klausen3, J Goelz3,D Schranz4, FA Mosthaf5 and JK Rockstroh1. 1 University of Bonn, Germany; 2 Private Practice, Duesseldorf, Germany; 3 Praxiszentrum Kaiserdamm, Berlin, Germany; 4 Private Practice, Berlin, Germany; and 5 Private Practice, Karlsruhe, Germany
Response rates under treatment with INF plus RBV appear to be lower in HIV/HCV-co-infected than in HCV-mono-infected patients. We analysed factors related to sustained response (SR) or non-response (NR) in a cohort of co-infected patients receiving peg INF plus RBV.
Within this open-label, uncontrolled, multicenter trial patients receive peg INF a-2b (PegIntron) 1.5 mg/kg/week plus 800 mg RBV/day.
HCV RNA, HIV RNA, CD4 cell count, blood count and liver enzymes are assessed at baseline and at weeks 4, 12, 24, 48, 60 and 72. 121 patients have been enrolled so far.
Here we present data on 58 patients who already completed 24 weeks follow- up.
15/58 (26%) patients showed sustained response with undetectable HCV RNA at week 24 of follow up. My recollection from poster is that 56% of patients in study were genotype 1. 43/58 patients showed non-response, of whom nine experienced relapse after showing end of treatment-response. Six patients discontinued prior to week 12 and were counted for as non-responders.
With regard to treatment outcome no differences in median age (SR: 40 years, range 29-58; NR: 39 years, range 23-58) or median CD4 cell count (SR: 457 cells, range 242-986 cells; NR: 451 cells, range 150-1288) at baseline could be observed.
Female participants experienced sustained response in 33% (7/21), compared with 22% (8/37) of male subjects. However, this difference was not statistically significant (P> 0.1).
Sustained response rates were significantly higher in patients with HCV genotype 2/3 (50%, 9/18), compared with patients infected with HCV genotypes 1/4 (17%, 6/36, P<0.01).
Patients showing an early treatment response with undetectable HCV RNA at week 12, were significantly more likely to achieve sustained response (15/25, 60%), than patients without (0/27, P<0.001).
Overall sustained response rates in HIV/HCV-co-infected patients treated with peg INF plus RBV are lower compared with historical data from HCV-mono-infected patients. However, several factors affect treatment outcome. Genotypes 2 and 3 favour sustained treatment response. Moreover, early response appears to be a predictive factor in co-infected as well as in HCV-mono-infected patients.
J Parra-Ruiz1, J Hernandez-Quero1, E Perez-Guzman2, R Granados-Monzon3, F Lozano-Leon4, M Alonso-Socas5, and E JimŽnez-Mejias6 on behalf of IT78047 Study Group. 1 San Cecilio Clinic Hospital, Granada Spain; 2 Puerta del Mar Hospital, Cadiz, Spain; 3 Dr Negr’n Hospital, Las Palmas de Gran Canaria, Spain; 4 Valme Hospital, Seville, Spain; 5 University Hospital, Tenerife, Spain; and 6 Virgen del Roc’o Hospital, Seville, Spain
This is a pilot, multicenter, prospective, and randomized trial of the efficacy of combination therapy with pegylated interferon alfa 2-a (pegIFN 2a) 180 mcg weekly plus two different doses of ribavirin (RBV) 1000 mg or 800 mg daily in patients with chronic hepatitis C (liver biopsy).The primary objective of the study is to determine the efficacy of treatment with peginterferon a-2a (Pegasys) combined with two different doses of ribavirin (Copegus) in producing sustained viral respomses, which is defined as sustained clearance of HCV 24 weeks after the end of treatment.
Patients had abnormal ALT Cd4s over 200. HIV RNA under control. 61 patients received 800/mg RBV/day vs 68 received 1000mg/day. 85% men in 800mg arm vs 77% in 1000mg arm. Average CD4 count was 575 in 800mg arm and 589 in 1000mg arm. 74% in 800mg arm are receiving HAART vs 87% in 1000mg arm. HCV RNA was 1.7-1.8 million copies/ml. HIV RNA was 4.5 log copies in 800mg arm vs 1.9 log copies in 1000mg arm. 54% had genotype 1, 28-31% genotype 2/3. 13% genotype 4. 86-91% had fibrosis stage F1/F2. 11% in 800mg arm had F3 stage vs 6% in 1000mg arm. 1.6% in 800mg arm had stage 4 vs 2.9% in 1000mg arm.
All the 144 patients included in the study, and prior to inclusion, had quantitative assay of HCV-RNA, by PCR, and genotyping. Those who had HCV-RNA positive at 24 weeks were considered as treatment failures and were excluded.
The primary efficacy endpoint was the rate of sustained virological responders, defined as the HCV- RNA clearance (by PCR) 6 months after the end of treatment. Secondary endpoint was the normalization of ALT levels.
Results were evaluated according to an intention-to-treat analysis. We present the results of an interim analysis at weeks 12 and 24. At week 12, 66 of 122 patients (54%) had HCV-RNA negative. At week 24, 65 of 110 (59%) patients had HCV-RNA negative.
Among patients with genotype 1, 28 of 59 (47%) had HCV-RNA negative, 27 of 31 (87%) among genotype 3 and 10 of 19 (52%) among genotype 4. After 24 weeks of treatment, the viral response rates in patients treated with RBV 800 and RBV 1000 mg/day were 55% and 62.7%, respectively. There were 22% withdrawals in the 800mg arm and 17% withdrawals in the 1000 mg arm.
None of the following baseline factors significantly affected the probability of achieving a viral response at 24 weeks: sex, body weight, age, HCV genotype, HCV RNA levels, CD4 count, receipt of HAART, ALT levels, extent of liver fibrosis. Adverse events were similar to those reported in trials with this combination in HCV monoinfected patients. The most common side effects were neutropenia (33), fever (21), flu-like symptoms (21), asthenia (18), GI events (14),. Anemia was reported in 6 patients. The majority of adverse events were mild (57%) or moderate (36%) in severity.
Withdrawal of medication was needed in 9 patients because of side effects and in 15 because of personal decision. A dose reduction of pegIFN 2a was necessary in 32 patients (29%). RBV was reduced in 19 (17%) Combination therapy with pegIFN 2a+RBV has a high early virological response rate with a good tolerability.
The authors concluded that the combination of peginterferon a-2a plus RBV )Copegus) is effective and well tolerated in co-infected patients. With respect to week 24 viral responses, a RBV dose of 1000/day appears to offer no advantage over a dose of 800mg/day. Final results of study are awaited with great interest.