Investigational Agents for HCV: Challenges and Opportunities
Explore the latest research and advancements in investigational agents for Hepatitis C Virus (HCV) presented by Dr. Susanna Naggie. Learn about the impact of HCV on individuals with HIV, innovative treatment approaches, and the evolving landscape of HCV therapy. Stay informed about the ongoing efforts to improve outcomes for patients with HCV and HIV coinfection.
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Slide 1 of 13 Investigational Agents for HCV: I Thought This Was Going To Get Easier Susanna Naggie, MD Assistant Professor of Medicine Duke Clinical Research Institute Durham, NC IAS USA From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA. From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA.
Slide 2 of 13 HIV & HCV 10 million people worldwide 30% of US patients with HIV have HCV Hepatitis C 180 million HIV 40 million Staples CT. Clin Infect Dis 1999 From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA.
Slide 3 of 13 D:A:D Study: Liver-Related Deaths in Persons with HIV 14.5% DAD Study Group, Arch Intern Med 2006 From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA.
Slide 4 of 13 HAART Era: Cirrhosis Risk From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA. Thein et al. AIDS 2008; 22:1979
Slide 5 of 13 Higher Health Care Utilization for HIV/HCV From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA. Katrak et al. CROI 2013 Abstract P219
Slide 6 of 13 NS3 Protease Inhibitors Serine protease (HIV aspartyl) Peptidomimetic Linear Macrocyclic High Potency Low barrier to resistance First Wave GT 1 Second Wave Multigenotypic (GT 3) From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA.
Slide 7 of 13 NS5B Polymerase Inhibitors Nucleoside (NI) vs Non-nucleoside (NNI) Moderate-High Potency Higher genetic barrier to resistance Multi- or pangenotypic Use in combination therapy 2-3 drugs Use in IFN-sparing/free From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA.
Slide 8 of 13 NS5A Inhibitors Activity in replication unknown Multiple possible mech of action Multi- to pangenotypic Moderate Potency Barrier to resistance Use in IFN-sparing/free From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA.
Slide 9 of 13 Telaprevir and Boceprevir In HCV Mono- Infected Subgroups: Phase III Summary 100 75-83[1,2] 80 63-74[7,8] 68-75[3,4] 53-62[3-4] SVR (%) 60 52-59[1,2] 29-38[1,6] 40 20 14[5]* 0 Relapser Naive White/ Nonblack Naive Black Partial Responder Null Cirrhotic Null Responder HIV- Responder coinfected Naive *Pooled TVR arms of REALIZE trial. 1. Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428. 2. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217. 3. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 4. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 5. Zeuzem S, et al. EASL 2011. Abstract 5. 6. Vierling JM, et al. AASLD 2011. Abstract 931. 7. Sulkowski MS, et al. Lancet Inf Dis 2013 [Epub]. From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA. 8. Sulkowski MS, et al. Ann Int Med 2013 [Epub].
Slide 10 of 13 PK Interactions: Telaprevir & ART ART Effects on ART Effects on TVR Recommendations AUC No significant No significant 78% Cmin AUC 26% 16% 11% Cmin 47% 25% 5% Efavirenz Etravirine* Rilpivirine* telaprevir dose Use standard doses Use standard doses 93% Atazanavir/r - 85% 20% 15% Use standard doses Darunavir/r 40% 42% 35% 13% Do Not Co-Administer FPV/r 47% 56% 13% 30% Do Not Co-Administer Lopinavir/r 34% 43% 54% 52% Do Not Co-Administer - Maraviroc 950% No significant Decrease dose of MVC to 150mg BID Use standard doses Raltegravir 31% - No significant Dolutegravir 25% 19% No significant Use standard doses Van Heeswijk et al. CROI 2011 Ab#119, ICAAC 2011 Ab# A1-1738a; Kakuda Clin Pharm 2012 Ab# O_18 Johnson Clin Pharm 2013 Ab#O_07, Vourvahis Clin Pharm 2013 Ab#O_17 From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA.
Slide 11 of 13 PK Interactions: Boceprevir & ART ART Effects on ART AUC 20% 23% 51% Effects on BOC AUC 19% 10% 22% Recommendations Cmin - 29% 34% Cmin 44% - 87% Efavirenz Etravirine Atazanavir/r Do Not Co-Administer Use standard doses Use with Caution ?? Darunavir/r Lopinavir/r 44% 34% 59% 43% 29% 44% 35% 35% Do Not Co-Administer Do Not Co-Administer FPV/r, TPV/r Maraviroc No PK Data, Interaction Possible - Do Not Co-Administer Decrease dose of MVC to 150mg BID Use standard doses Use standard doses No significant 300% 57% 7% Raltegravir Dolutegravir 45% 8% No 50% Not available Kasserra et al. 18th CROI 2011 Ab# 118; Hulskotte et al. 19th CROI 2012 Ab# 771LB; Hammond Clin Pharm 2012 Ab# O_15 Garraffo Clin Pharm 2013 Ab#O_15, , Vourvahis Clin Pharm 2013 Ab#O_17 From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA.
Slide 12 of 13 What about SOF in HIV/HCV? ARV SOF Phase IIB SOF + P/R X 12W Na ve, GT 1-3 NCT01565889 Phase III SOF + WBR X 12-24W Na ve GT 1-4, Experienced GT 2,3 20% Cirrhotic ARV ATR DRV/r RAL RPV TDF EFV AUC N/A 3% 27% 43% 5% 6% 5% 2% 25% 3% 5% Cmax N/A 3% AUC 6% 37% 45% Cmax 19% 2% 10% 21% N/A N/A N/A N/A Kirby et al. AASLD 2012 Abstract #1877 From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA.
Slide 13 of 13 Simeprevir and ART? ARV SOF Recommendation ARV EFV DRV/r RAL RPV TDF AUC 10% 18% 8% 12% 18% Cmax 3% 4% 3% 4% 19% AUC 71% 259% 11% 6% 14% Cmax 51% 79% 7% 10% 15% Do not co-administer Do not co-administer Use standard doses Use standard doses Use standard doses Phase III Study: Rilpivirine (15%), Raltegravir (87%), Maraviroc, Enfuvirtide, NRTIs Ouwerkerk-Mahadevan et al. IDSA 2012 Abstract #49 From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA.
