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Read Now: News and Research From ICAAC 2014

Cure Rates With Pipeline HCV Drugs: Reports From AASLD

November/December 2012

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HIV/HCV Coinfection

Final results from a Phase 2 trial of telaprevir plus peginterferon and ribavirin in HIV/HCV coinfected people were presented at AASLD.

In this trial, there were no relapses between 12 and 24 weeks post-treatment: 74% of people who received telaprevir-based triple therapy versus 45% of people given peginterferon and ribavirin plus placebo achieved SVR-24.

Telaprevir levels were similar in study participants in the no-ART arm as well as those taking a boosted atazanavir-or efavirenz-based regimen; in turn, antiretroviral concentrations were not significantly altered by telaprevir, confirming results of earlier drug-drug interaction studies.22

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Sofosbuvir is already being studied in HIV/HCV coinfected people with HCV genotypes 2 and 3; a clinical trial is comparing 12 vs. 24 weeks of sofosbuvir and ribavirin is ongoing.23

Results from drug-drug interaction (DDI) studies of sofosbuvir and commonly used antiretroviral agents were presented at AASLD. There were no clinically significant interactions between sofosbuvir and efavirenz, rilpivirine, boosted darunavir, raltegravir, tenofovir and emtricitabine in healthy volunteers.24

Pharmacokinetics and DDIs may be different in people with hepatitis C -- especially those with advanced liver damage -- and HIV-positive people, compared with healthy volunteers. Nonetheless, these results suggest that these drugs can be co-administered with sofosbuvir, though careful monitoring in clinical trials is still warranted.

Hopefully, the near future will bring more interferon-free trials to HIV/HCV coinfected people.


Table 2. Update: Interferon-Free Regimens in HCV Genotype 1, Treatment-Naive
Study, Sponsor & Regimen Population and Size SVR (at 4,12 or 24 Weeks Post-Treatment) SVR: HCV Genotype 1a vs. 1b SVR: IL-28b CC vs. Non-CC Comment
AVIATOR Phase 2b.
Abbott Laboratories
Drugs (3 or 4): ABT-450/r (boosted protease inhibitor) with or without ABT-267 (NS5a inhibitor) with or without ABT-333 (non-nucleoside polymerase inhibitor) with or without ribavirin.
Duration: 8, 12 or 24 weeks
Non-cirrhotic (N=438; 358 were treatment-naive; for null responder data see Table 3. Update: Interferon-Free Regimens in HCV Genotype 1, Treatment Experienced). SVR-1287.5% in the 8-week 4-drug arm (N=80) vs. 97.5% in the 12-week, 4 drug arm (N=79). 8-week, 4-drug arm:86% in G1a versus 96% in G1b.12-week, 4-drug arm: 98% in G1a vs. 100% for G1b. In all 12-week, 3-drug arms: 82% to 88% for G1a vs. 100% for G1b. 8-week, 4-drug arm:96% in IL28b-CC vs. 85% in non-CC.12-week, 4-drug arm: 100% in IL-28B CC vs. 97% in non-CC. In 12-week, 3-drug arms: 86% to 100% in IL-28B CC vs. 85% to 88% in non-CC. Kowdley et al.5
SOUND-C2 Phase 2b.
Boehringer-Ingelheim
Drugs: faldaprevir (protease inhibitor) with BI 207127 (non-nucleoside polymerase inhibitor) with or without ribavirin.
Duration: 16, 28 or 40 weeks.
(N=362; 329 non-cirrhotic and 33 with compensated cirrhosis). SVR-12: 39% to 69%non-cirrhotic (highest SVR-12 in the 28-week, twice- daily 207127 arm; N=78). 33% to 67%(in cirrhotic participants; the highest SVR-12 in the 28-week, twice daily 207127 arm). In 28-week, twice-daily 207127 arm: 85% for G1b vs. 43% for G1a. In 28-week, twice-daily 207127 arm: 84% in IL28b CC vs. 64% in non-CC. Zeuzem et al.6
AI444-040 Phase 2a.
Bristol-Myers Squibb/ Gilead Sciences
Drugs: daclatasvir (NS5a inhibitor) with sofosbuvir (nucleotide polymerase inhibitor) with or without ribavirin.
Duration: 12 or 24 weeks.
Non-cirrhotic(N=126). SVR-4:95% to 98% in 12-week treatment groups (N=82).SVR-12: 93% to 100% in 24-week treatment groups (N=44). No impact on SVR. No impact on SVR. Sulkowski et al.7 Gilead is now only developing an in-house regimen.
AI443-014 Phase 2
Bristol-Myers Squibb
Drugs: daclatasvir (NS5a inhibitor) with asunaprevir (protease inhibitor) with BMS-791325 (non-nucleoside polymerase inhibitor).
Duration: 12 or 24 weeks.
Non-cirrhotic(N=32) SVR-424-week dosing group (N=16): 94% SVR-24
12-week dosing group (N=16): 94%
No impact on SVR. No impact on SVR. Everson et al.8
ELECTRON Phase 2
Gilead Sciences
Sofosbuvir (nucleotide polymerase inhibitor) with ribavirin with or without GS-5884 (NS5a inhibitor)
Duration: 12 weeks
Non-cirrhotic(N=50) SVR-4100% (25/25) for triple therapy with sofosbuvir plus RBV and GS-5885. SVR-12 84% (21/25) for sofosbuvir plus RBV. No impact on SVR. No impact on SVR. Gane et al.9
SPARE Phase 2
Gilead Sciences/NIH
Drugs: sofosbuvir (nucleotide polymerase inhibitor) with weight-based ribavirin dosing (WBD) or low-dose ribavirin (600 mg).
Duration: 24 weeks.
(N=60) Most were African American, IL-28B non-CC and non-cirrhotic (N=43); a small group had advanced fibrosis or compensated cirrhosis (N=13). SVR-12Part 1. Non-cirrhotic, WBD ribavirin: 90% (9/10). Part 2. WBD RBV (included 24% with advanced fibrosis): 72% (18/25). Part 2. Low-dose RBV (including 28% with advanced fibrosis): 56% (14/25). No impact on SVR. No impact on SVR. Osinusi et al.10
Vertex Pharmaceuticals
Drugs: telaprevir (protease inhibitor) with VX-222 (non-nucleoside polymerase inhibitor) with ribavirin.
Duration: response guided, either 12 weeks triple (N=11) or 12 weeks triple plus 24 weeks of PEG/RBV if HCV RNA detectable at week 2 or 8 (N=27).
Non-cirrhotic (N=46). SVR-12Overall 72%33/46. 12-week group: 82% (9/11). 36-week group: 89% (24/27). 100% (5/5 for 12 weeks of triple in G1b vs. 67% (4/6) in G1a.85% (11/13) in 36-week group in G1b vs. 93% (13/14) in G1a. Data not broken out by IL-28b genotype. Sulkowski et al.11


Table 3. Update: Interferon-Free Regimens in HCV Genotype 1, Treatment-Experienced
Study, Sponsor & Regimen Population and Size SVR (at 4,12 or 24 Weeks Post-Treatment) SVR: HCV Genotype 1a vs. 1b SVR: IL-28b CC vs. Non-CC Comment
AVIATOR Phase 2
Abbott
ABT-450/r (boosted protease inhibitor) with ABT-267 (NS5a inhibitor) with ribavirin with or without ABT-333 (non-nucleoside polymerase inhibitor)
Duration: 12 or 24 weeks.
Null responders, non-cirrhotic (N=133). SVR-1293% (42/45) for 4-drug regimen.89% (40/45) for ABT 450/r, ABT-267 and ribavirin(12-week treatment group only; follow up of 24-week treatment group is ongoing). 100% in G1b vs. 81% to 89% in G1a. 100% in IL28B CC vs. 89% to 93% in non-CC. Kowdley et al.5 Regimen slightly more effective in G1b vs. G1a, and for IL28b CC vs. non-CC.
AI447-011 Phase
Bristol-Myers Squib
Drugs: daclatasvir (NS5a inhibitor) with asunaprevir (protease inhibitor), once- or twice-daily.
Duration: 24 weeks.
Null responders (N=101), HCV genotype 1b only (N=38; 16%, or 8 people had advanced fibrosis). SVR-12, 65% (13/20) to 78% (14/18) for once- versus twice-daily asunaprevir. Enrollment in asunaprevir/daclatasvir arms limited to G1b due to lack of efficacy in G1a. All but one person was IL28b non-CC. Lok et al.12 In this trial, the same combination, plus ribavirin, was given to people with HCV genotypes 1a and 1b.Peginterferon was added in G1a due to high rates of viral, breakthrough; in HCV genotype 1b, SVR-4 was 100%.
ELECTRON Phase 2
Gilead Sciences
Drugs: GS-5885 (NS5a inhibitor) with sofosbuvir (nucleotide polymerase inhibitor) with ribavirin
Duration: 12 weeks
Null responders, (N=9), non-cirrhotic SVR-4, 100% (3/3). Gane et al.9 Only 3/9 null responders have completed treatment; the other 6 are being followed.
MATTERHORN Phase 2.
Hoffman-La Roche
Drugs: danoprevir/r (boosted protease inhibitor) with mericitabine (nucleoside polymerase inhibitor) with ribavirin
Duration: 24 weeks
Partial (N=23) and null responders (N=32) HCV genotype 1b, non-cirrhotic. SVR-12Partial responders: 39% (9/23)Null responders: 55% (17/31) All G1a patients added peginterferon due to high rates of virologic breakthrough and are not included. >90% were IL28b non-CC. Feld et al.13 Baseline viral load higher in partial vs. null responder.
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This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.
 

 

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