Treatment of HCV in HIV/HCV Coinfection Michael S. Saag, MD Associate Dean, Global Health Professor of Medicine Director, Center for AIDS Research University of Alabama at Birmingham Birmingham, Alabama FINAL AS OF: 11/15/17 Learning Objectives After attending this presentation, learners will be able to: Determine when to treat HCV in persons coinfected with HIV Pick the best regimen to treat HCV in the setting of HIV co-infection Decide which HCV regimens to use based on drug-drug interaction determinations Slide 3 of 24 A Tale of Two Viruses HIV Sex > Blood Targets immune cells Years to clinical illness High levels of viremia Frequently mutates 1 cure after BMT HCV Blood > Sex Targets liver cells Decades to clinical illness High levels of viremia Frequently mutates > 90% Cured Slide 4 of 24 Louisville, Kentucky, November 17, 2017 1
HIV associated with higher rates of HCVrelated liver fibrosis HIV+HCV HCV Slide 5 of 24 Kirk et al. Ann Intern Med 2013; 158:658-666 HIV Co-infection Shortens Survival in HCV-related Decompensated Cirrhosis Pineda JA, Romero-Gómez M, Díaz-García F, et al. HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis. Hepatology. 2005;41:779-789. Slide 6 of 24 ART in HIV/Hepatitis C Virus Coinfection When to Start ART should be initiated regardless of CD4 count HCV rx as soon as possible after immune recovery (CD4 > 200 cells/ul) or CD4 > 100 cells /ul and HIV RNA < 50 c/ml for more than a year What to Start Same initial HCV regimens are recommended for HCV mono-infection and HIV/HCV co-infection Check for DDIs No HCV PI s in those with Child-Pugh class B and C Slide 7 of 24 aidsinfo.nih.gov Louisville, Kentucky, November 17, 2017 2
Key DAA Trials in HIV: Comparable SVR12 Rates with Mono-infection Studies Slide 8 of 24 Simeprevir Ledipasvir Daclatasvir P/r/O + D DDI CYP3A4, OATP1B1/3 P-gp and BCRP Inhibitor/ P-gp and BCRP Inhibitor of OATP1B1/3, BCRP, P-gp and CYP3A4 Inhibit/Sub of UGT1A1,OATP1B1/3, BCRP, CYP3A4, CYP2C8, P-gp ATV/r No data No data LDV ; ATV DCV * ATV ; PAR DRV/r SIM ; DRV SOF ; DRV LDV ; DRV ALLY-2 DRV ; PAR LPV/r No data No data No data ALLY-2 LPV ; PAR TPV/r No data No data No data No data No data EFV SIM ; EFV SOF ; EFV ION-4 DCV * No PK data** RPV SIM ; RPV SOF ; RPV LDV ; RPV ALLY-2 PAR ; RPV ETV No data No data No data No data* No data RAL SIM ; RAL SOF ; RAL LDV ; RAL ALLY-2 PrOD ; RAL ELV/cob No data Cobi ; SOF LDV ; SOF No data No data i DLG No data No data LDV ; DOL ALLY-2 PAR ; DOL Slide courtesy of Jennifer Kiser MVC No data No data No data No data No data TDF SIM ; TFV SOF ; TFV LDV ; TFV DCV ; TFV PrOD ; TFV Slide 9 of 24 Elbasvir/ Grazoprevir Velpatasvir/ Velpatasvir/ / Voxilaprevir Ledipasvir/ P/r/O + D DDI CYP3A4, P-gp, OATP1B1/3; Inhibitor of BCRP, P-gp, CYP2C8, 3A4, UGT1A1 P-gp, BCRP, OATP, CYP2B6, 2C8, 3A4; Inhibitor of P-gp, BCRP, OATP P-gp, BCRP, OATP, CYP2B6, 2C8, 3A4; Inhibitor of P-gp, BCRP, OATP Inhibitor/ P-gp and BCRP Inhibit/Sub of UGT1A1,OATP1B1/3, BCRP,CYP3A4, CYP2C8, P-gp ATV/r GRZ & ELB, ATV VEL ; ATV ATV LDV ; ATV ATV ; PAR DRV/r LPV/r GRZ & ELB ; DRV GRZ & ELB ; DRV VEL ; DRV Vox ; DRV LDV ; DRV DRV ; PAR VEL ; LPV No Data No data LPV ; PAR TPV/r No data No data No data No data No data EFV GRZ & ELB, EFV VEL ; EFV No data ION-4 No PK data** RPV GRZ & ELB ; RPV VEL ; RPV VEL ; RPV V ox LDV ; RPV PAR ; RPV ETV No data No data No data No data No data RAL GRZ & ELB ; RAL VEL ; RAL No data LDV ; RAL PrOD ; RAL ELV/cobi No data VEL ; SOF Vox ; Cobi LDV ; SOF No data Slide 10 of 24 Louisville, Kentucky, November 17, 2017 3
Case 1 49 y/o African-American woman with HIV/HCV coinfection HIV: Suppressed on TAF/FTC + darunavir/cobi CD4 435 cells/ul No other meds HCV: Genotype 1b infection Fibrosure- confounded Fibroscan - 8 kpa Slide 11 of 24 What would be your choice of HCV therapy? 1. Daclatasvir + sofosbuvir 3. Ledipasvir / sofosbuvir FDC 4. Paritaprevir/r/ombitasvir FDC + dasabuvir 0% 57% 43% 0% 0% Slide 13 of 24 Daclatasvir + sofo... Elbasvir/grazoprevir Ledipasvir / sofos... Paritaprevir/r/om... Simeprevir + sofo... What would be your choice of HCV therapy? 1. Daclatasvir + sofosbuvir 3. Ledipasvir / sofosbuvir FDC 4. Paritaprevir/r/ombitasvir FDC + dasabuvir Slide 15 of 24 Daclatasvir + sofo... Elbasvir/grazoprevir 0% 0% 0% 0% 0% Ledipasvir / sofos... Paritaprevir/r/om... Simeprevir + sofo... Louisville, Kentucky, November 17, 2017 4
Elbasvir/ Grazoprevir Velpatasvir/ Ledipasvir/ P/r/O + D DDI CYP3A4, P-gp, OATP1B1/3; Inhibitor of BCRP, P-gp, CYP2C8, 3A4, UGT1A1 P-gp, BCRP, OATP, CYP2B6, 2C8, 3A4; Inhibitor of P-gp, BCRP, OATP Inhibitor/ P-gp and BCRP Inhibit/Sub of UGT1A1,OATP1B1/3, BCRP, CYP3A4, CYP2C8, P-gp ATV/r GRZ & ELB, ATV VEL ; ATV LDV ; ATV ATV ; PAR DRV/r GRZ & ELB ; DRV VEL ; DRV LDV ; DRV DRV ; PAR LPV/r GRZ & ELB ; DRV VEL ; LPV No data LPV ; PAR TPV/r No data No data No data No data EFV GRZ & ELB, EFV VEL ; EFV ION-4 No PK data** RPV GRZ & ELB ; RPV VEL ; RPV LDV ; RPV PAR ; RPV ETV No data No data No data No data RAL GRZ & ELB ; RAL VEL ; RAL LDV ; RAL PrOD ; RAL ELV/cobi No data VEL ; SOF LDV ; SOF No data DLG GRZ & ELB ; DLG VEL ; DLG LDV ; DOL PAR ; DOL Slide courtesy of Jennifer Kiser MVC No data No data No data No data Slide TDF 16 of 24 GRZ & ELB ; TFV VEL ; TFV LDV ; TFV PrOD ; TFV Case 2 49 y/o African-American woman with HIV/HCV coinfection HIV: Suppressed on TAF/FTC + Dolutegravir CD4 435 cells/ul No other meds except omiprazole 40 mg /bid HCV: Genotype 1a infection Fibrosure- 0.45 Fibroscan - 8 kpa No RAVs Slide 17 of 24 What would be your choice of HCV therapy? 1. Velpatasvir / sofosbuvir 3. Ledipasvir / sofosbuvir FDC 4. Paritaprevir/r/ombitasvir FDC + dasabuvir Slide 19 of 24 45% 27% 18% 9% 0% Velpatasvir / sofo... Elbasvir/grazoprevir Ledipasvir / sofos... Paritaprevir/r/om... Simeprevir + sofo... Louisville, Kentucky, November 17, 2017 5
Case 2 What would be your choice of HCV therapy? 1. Velpatasvir / sofosbuvir 3. Ledipasvir / sofosbuvir FDC 4. Paritaprevir/r/ombitasvir FDC + dasabuvir Slide 20 of 24 Elbasvir/ Grazoprevir Velpatasvir/ Ledipasvir/ P/r/O + D DDI ARV Interaction Score Card 2016 CYP3A4, P-gp, Inhibitor/ OATP1B1/3; Inhibitor of P-gp, BCRP, OATP, CYP2B6, P-gp BCRP, P-gp, CYP2C8, 3A4, 2C8, 3A4; Inhibitor of P-gp, and BCRP UGT1A1 BCRP, OATP Inhibit/Sub of UGT1A1,OATP1B1/3, BCRP, CYP3A4, CYP2C8, P-gp ATV/r GRZ & ELB, ATV VEL ; ATV LDV ; ATV ATV ; PAR DRV/r GRZ & ELB ; DRV VEL ; DRV LDV ; DRV DRV ; PAR LPV/r GRZ & ELB ; DRV VEL ; LPV No data LPV ; PAR TPV/r No data No data No data No data EFV GRZ & ELB, EFV VEL ; EFV ION-4 No PK data** RPV GRZ & ELB ; RPV VEL ; RPV LDV ; RPV PAR ; RPV ETV No data No data No data No data RAL GRZ & ELB ; RAL VEL ; RAL LDV ; RAL PrOD ; RAL ELV/cobi No data VEL ; SOF LDV ; SOF No data DLG GRZ & ELB ; DLG VEL ; DLG LDV ; DOL PAR ; DOL Slide courtesy of Jennifer Kiser MVC No data No data No data No data Slide TDF 21 of 24 GRZ & ELB ; TFV VEL ; TFV LDV ; TFV PrOD ; TFV Case 3 49 y/o African-American woman with HIV/HCV co-infection HIV: Suppressed on TAF/FTC + Dolutegravir CD4 235 cells/ul No other meds HCV: Genotype 1a infection Fibrosure- 0.83 Fibroscan - 15 kpa Ascites on examination / Splenomegaly on Ultrasound No RAVs Slide 22 of 24 Louisville, Kentucky, November 17, 2017 6
What would be your choice of HCV therapy? 1. Glecaprevir / pibrentasvir 3. Velpatasvir / sofosbuvir FDC 4. Paritaprevir/r/ombitasvir FDC + dasabuvir Slide 24 of 24 Glecaprevir / pibr... 64% Velpatasvir / sof... Elbasvir/grazoprevir 36% 0% 0% 0% Paritaprevir/r/om... Simeprevir + sofo... Case 3 What would be your choice of HCV therapy? 1. Glecaprevir / pibrentasvir 3. Velpatasvir / sofosbuvir FDC 4. Paritaprevir/r/ombitasvir FDC + dasabuvir Slide 25 of 24 Perfect Storm for Sexual Transmission of HCV in MSM Sex HIV Drugs Crystal Meth Cocaine Opioids Higher levels of virus in plasma and semenimmune deficiency, especially at GI mucosa Slide 26 of 24 Louisville, Kentucky, November 17, 2017 7
HCV Re-infection Among HIV+ MSM Slide 27 of 24 HCV Incidence among HIV+ MSM in San Diego Higher incidence if crystal meth used Chaillon CROI 2017 Slide 28 of 24 Louisville, Kentucky, November 17, 2017 8