5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Cape Town, South Africa, 19 – 22 July 2009
WEPEB235
Corresponding Author: Jürgen K. Rockstroh Immunologische Ambulanz Medizinische Klinik und Poliklinik I Universitätsklinikum Bonn Germany Tel.: +49-228-287-16558 Fax: +49-228-287-15034 email: juergen.rockstroh@ukb.uni-bonn.de
The effect of Nucleoside free HAART on the treatment of chronic HCV infection
Martin Vogel1, Golo Ahlenstiel1, Gerd Klausen2, Thomas Lutz3, Dirk Schürmann4, Christoph Stephan5, Christoph Mayr6, Axel Baumgarten7, Peter Buggisch8, Hartwig Klinker9, Christine John10, Jörg Gölz11, Pavel Khaykin5, Markus Bickel5, Jürgen Kurt Rockstroh1
1) Bonn University, Department of Internal Medicine I, Bonn, 2) Praxis Hintsche / Klausen, Berlin, 3) Infektiologikum, Frankfurt / Main, 4) Charité Universitätsmedizin, Berlin, 5) University of Frankfurt / Main, Frankfurt / Main, 6) Ärzteforum Seestraße, Berlin, 7) Praxis Dupke / Baumgarten / Carganico, Berlin, 8) Institut für Interdisziplinäre Medizin (ifi), Hamburg, 9) University of Würzburg, Würzburg, 10) Practice John, Berlin, 11) Praxiszentrum Kaiserdamm, Berlin, Germany
Background:
Tables and Figures:
The impact of nucleoside analogues on the treatment of chronic HCV infection with pegylated interferon and ribavirin is controversially discussed.
Chronic HCV Methods:
HIV+ HAART HIV+ no HAART 2 SC, 3 WD, 46 patients HIV1 SC, 50 patients
NUC-free HAART 1 SC, 5 WD, 20 patients NUC-containing HAART 1 SC, 3 WD, 48 patients
Figure 1: Trial flow chart. HIV+ HIV-coinfected patients; HIV- HCV-monoinfected patients; HAART highly active antiretroviral therapy NUC nucleoside(s); ۞ 1:1 randomization; SC scrren failure; WD withdrawal
Prospective, partially randomized multi-center study (figure 1). HIV-negative patients (group A) were compared to HIV-positive patients without HAART (group B) and with HAART (group C). Group C was randomized to nucleoside-free HAART (double PI or PI/NNRTI, group C1) and nucleoside containing HAART (group C2). HIVpositive patients were treated with 180 µg pegylated interferon alfa-2a and 800 mg ribavirin; treatment duration was 24 weeks for genotypes 2 or 3 and 48 weeks for genotypes 1 or 4. After amendment I genotype 2 and 3 infections were treated 48 weeks and after amendment II weight based ribavirin was prescribed for genotype 1 or 4 infections. SVR was analyzed per protocol (C1 and C2 arm as treated, missing=failure).
Results:
HIVN=50 Sex (male) Age (years) Transmission risk IVDU sexual blood products unknown PI/NNRTI/3xNUC AZT d4T ABC TDF CD4 count (/µl) HIV-RNA (log10) ALT (IU/ml) HCV-Genotype 1/4 HCV-RNA (log10) 60* * 41 (33 - 49)
HIV+ no HAART N=46 72 39 (33 - 43) *
HIV+ NUC-cont N=48 77 41 (39 - 45) *
HIV+ NUC-free N=20 85 43 (39 - 46) *
Table 1: Baseline characteristics of patients according to treatment arm (as treated) *p< 0.05 HIV- vs HIV+; *p<0.05 no HAART vs. NUC-cont. vs. NUC free
40 8 10 26 61 (40 - 92) 56 5.7 (5.2 - 6.2)
35 2 2 59 * 580 (436-755)* 3.9 (3.3 - 4.3) 64 (31 - 121) 63 5.7 (5.2 - 6.0)
25 10 6 58 58/31/13 33 17 31 46 490 (361-573)* * 1.7 75 (51 - 120) 63 5.4 (5.1 - 6.0)
5 10 85 100/5/390 (297-601)* * 1.7 75 (54 - 124) 55 5.8 (5.4 - 6.6)
A total of 189 patients were screened / randomized; 9 patients were screen failures, 12 patients withdrew consent and 4 patients had incomplete data; 164 patients (group A = 50, B = 46, C1 = 20, C2 = 48) received at least one dose of pegylated interferon / ribavirin and were available for analysis (figure 1). Comparing baseline demographics between treatment groups (table 1) HIV-negative patients were less often male and HIV-positive patients without HAART were younger and had higher CD4-cell counts than HIV-positive on HAART. In the per protocol analysis comparable SVR rates were reached among HIV- and HIV+ in 54% of cases in both groups. Whereas the rate of SVR was not different between groups B and C (59% vs. 52%) a significant difference was observed between C1 and C2 (75 vs. 42%; p=0.012). Except for level of HCV-RNA (higher in the NUC-free arm) no differences were observed comparing NUC-free vs. NUC-containing HAART with regard to frequency of HCV-genotype 1/4, use of weight adapted RBV, treatment duration, number of adverse events or rate of treatment discontinuations due to adverse events. Post-hoc analysis of group C2 according to SVR-status showed that patients with SVR had significantly lower baseline HCV-RNA and more often HCV genotype 2 or 3 than patients without SVR (table 2). Though patients on ABC less often achieved SVR, this was not statistically significant.
Conclusions:
HIV-neg 100 90 80 70 60 50 40 30 20 10 0 84 74 67 73
HIV-pos 90
no HAART
NUC-cont 85
NUC-free
p = 0.012
Percent of Patients
72 71 74 63 54 54 59 42
75
Figure 2: Treatment response rates according to treatment arm (as treated) EVR early virological response, ETR end of treatment response SVR sustained virological response
EVR
No SVR n=28 Sex (male) Age (years) Transmission risk IVDU sexual blood products unknown HCV-Genotype 1/4 HCV-RNA (log10) Weight based RBV HAART 3x / 4x NUC AZT d4T ABC TDF CD4 (/µl) 20 (71%) 42 (39 - 45) SVR n=20 16 (80%)
ETR
p-value
SVR
Table 2: Analysis of NUC-cont. Patients (C2) SVR vs. No SVR)
0.635 0.966
41 (37 - 45)
8 (29%) 3 (11%) 2 (7%) 15 (54%) 22 (79%) 5.7 (5.3 - 6.5) 17 (61%)
4 (20%) 2 (10%) 1 (5%) 13 (65%) 8 (40%) 5.1 (4.6 - 5.4) 8 (40%)
0.964
0.003 < 0.001 0.157
High SVR-rates, comparable to HIV-negative patients, were reached in 54% of HIV-positive patients. NUC-free HAART resulted in higher SVR-rates compared to NUC-containing HAART, though a selection bias towards the NUC-free arm cannot be ruled out.
4 (14%) 11 (39%) 5 (18%) 11 (39%) 12 (43%) 524 (361 - 655)
2 (10%) 5 (25%) 3 (15%) 4 (20%) 11 (55%) 459 (364 - 566)
0.658 0.301 0.793 0.155 0.406 0.341