Martel-Laferrière V, Brinkley S, Bichoupan K, Posner S, Stivala A, Perumalswami P, Schiano T, Sulkowski M, Dieterich DT, Branch AD

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1 On-treatment and Sustained Virologic Response Rates of Telaprevir-based HCV Treatments Do Not Differ Between HIV/HCV Co-infected and HCV Mono-infected Patients Martel-Laferrière V, Brinkley S, Bichoupan K, Posner S, Stivala A, Perumalswami P, Schiano T, Sulkowski M, Dieterich DT, Branch AD

2 Disclosures Conflicts of interest No disclosures relevant to this study Funding Andrea D. Branch: NIH DA01095 and DK09017 Valérie Martel-Laferrière: 2011 AMMI Canada/Pfizer Post Residency Fellowship and 2012 Grant of the CHUM Foundation

3 Background Phase III trials of telaprevir/peg-interferon/ribavirin in HIV/HCV co-infected population are ongoing In naive patients (n=8) Rapid virological response (RVR): 68% Early virological response (EVR): 79% SVR 24: 74% Adverse events: Discontinuations for AEs were rare: 1 patient discontinued telaprevir only and 2 discontinued all medications Anemia: < 10 g/dl: 18% < 8.9 g/dl or decrease > 4.5g: 1patient Rash: 4% Sulkowski M, et al. AASLD, 2012

4 Aim To determine virologic responses to triple therapy with telaprevir (TVR) in HIV/HCV co-infected patients in a real-life setting

5 Study Design Observational study, Icahn School of Medicine at Mount Sinai and Johns Hopkins University Patients who started therapy before December 2011 HCV viral load measured at baseline, week-4, -12, -24 and -48 and 12 weeks post-treatment by Roche Ampliprep test (LOQ: 4 IU/mL) Data collected with IRB approval, analyzed in SPSS

6 End Points Undetectable HCV RNA at week-4 (RVR), week-12 (EVR), week-24, EOT and SVR-12 Side effects and early discontinuations Virologic failure Non-response Viral load > 1,000 IU/mL at week-4 or -12 Viral RNA detectable at week-24 Virologic breakthrough Viral load detectable after being undetected

7 Definitions: Fibrosis and Anemia Advanced fibrosis/cirrhosis FIB-4 values.25 Anemia Hemoglobin <1.5 g/dl (men), <12 g/dl (women) Severe anemia, hemoglobin < 9 g/dl and/or decrease 4.5 g/dl

8 Baseline Characteristics Co-infected (N = ) Mono-infected (N = 117) P- value Median age (IQR) 57 (52-59) 56 (51-61) 0.82 Male (% of total) 26 (78.8%) 79 (67.5%) 0.21 Race (% of total) White Black Other 16 (48.5%) 14 (42.4%) (9.1%) 65 (55.6%) 19 (16.2%) 4 (28.2%) <0.01 Prior treatment response (% of total) Naive Relapser Non responder/intolerant (9.1%) 5 (15.2%) 25 (75.8%) 6 (0.8%) 2 (19.7%) 58 (49.6%) 0.02 Bridging fibrosis/cirrhosis (% of total) 16 (48.5%) 40/11 (5.4%) 0.17 Baseline HCV viral load log 10 IU/mL (IQR) 6.46 ( ) 6.46 ( ) 0.42

9 Baseline HIV Status Median CD4 count cells/μl (IQR) HIV VL (% of total) - Undetectable/< 20 copies/ml - < 1000 copies/ml ART regimen change required prior to start of triple therapy (% of total) Co-infected (n = ) 478 (62-76) 24/0 (80%) 0/0(100%) 17 (51.5%)

10 Virologic Responses Trend for better virologic responses in co-infected patients is potentially explained by a selection bias

11 CD4 + T cell count, cells per ul Baseline CD4 + T cell count does not affect SVR12 rate Treatment Failure SVR12

12 Virologic Outcome by HIV Regimens: Numbers are too small to reach conclusions RVR EVR Week- 24 EOT SVR12 NRTI + atazanavir ritonavir (1) 5 (9%) 8 (62%) 10 (77%) 8 (62%) 7 (54%) NRTI + efavirenz (5) 1 (20%) NRTI + raltegravir (6) (50%) NRTI + raltegravir + atazanavir ritonavir (5) (60%) (60%) 4 (67%) 5 (100%) (60%) 4 (67%) 5 (100%) (60%) 4 (67%) 5 (100%) (60%) 2 (%) 5 (100%) Other (4) 2 (50%) (75%) (75%) (75%) (75%)

13 HIV co-infection did not increase rates of discontinuation or severe anemia HIV/HCV coinfected patients HCV monoinfected patients p- value Discontinuation due to side effects (%) 8 (24.2%) 16 (1.7%) 0.14 Hospitalization (%) 9 (27.2%) 21 (17.9%) 0.42 Emergency room visits (%) 6 (18.2%) 16 (1.7%) 0.52 Anemia (%) 29 (87.8%) 107 (91.5%) 0.5 Severe anemia (%) 15 (45.5%) 68 (58.1%) 0.20 Rash (% of total) 5 (15.2%) 40 (4.2%) 0.04 Rectal symptoms (%) 4 (12.1%) 51 (4.6%) <0.01 Reduced rates of rash in co-infected patients might be due to reduced immune responses. Alternatively, HIV + patients may be more used to drug side effects and inclined to complain less.

14 Rate of SVR12 in our mono-infected patients was lower than in clinical trials Clinical trials Our study Naives 7.5% 52.7% Relapsers 8% 47.8% Non responders/ intolerant Total * Projection of a matched population 44% 4.5% 60.7%* 42.7% Possible explanations Higher prevalence of African Americans and advanced fibrosis/cirrhosis High rates of relapses among the previous relapsers Patients less well selected than patients in clinical trials Sherman et al. NEJM, 2011 Jacobson et al. NEJM, 2011 Zeuzem et al. NEJM, 2011

15 Conclusions On-treatment responses and SVR12 rates were statistically similar between co- and mono-infected patients even if they tended to be better in co-infected patients A selection bias in favor of adherent HIV infected patients is possible A higher percentage of cirrhotic patients and African Americans probably explain our lower SVR12 rates in mono-infected patients compared to clinical trials Rates of major events (severe anemia and treatment discontinuation) were similar Rash and rectal symptoms tended to be less common in coinfected patients