New York State HCV Provider Webinar Series

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2 New York State HCV Provider Webinar Series Treatment of HCV/HIV Co-Infection Dost Sarpel, MD Division of Infectious Disease Viral Hepatology Milford Regional Medical Center

3 Objectives Review the epidemiology of HCV and HIV/HCV coinfection Discuss the burden of HIV/HCV co-infection Discuss the treatment considerations for co-infected population Understand drug drug interactions that are unique to the HIV/HCV co-infected population

4 Epidemiology of HCV and HCV/HIV Co-Infection

5 Case #1 26 year old HIV+ MSM presents to your office for routine follow up. His HIV is well controlled on FTC/TAF + DTG with CD4 550 and an undetectable HIV VL. He is sexually active with multiple partners. Rarely uses condoms. Recently treated for chlamydia. Occasional drug use.

6 Which of the following is true? A) HIV+ status increases risk of HCV infection through IVDU B) HIV+ status increases risk of HCV infection through high risk sexual practices C) Both A&B D) HIV+ status has no effect on HCV transmission risk

7 HCV Prevalence in the U.S % unaware of HCV status million Reported (NHANES) 5-7 million True Sarpel, et al. Expert Review of Anti-Infective Therapy

8 What is the Gap Between Reported and True Prevalence Attributable to? A failure to count the following persons: Homeless Incarcerated Immigrant Nursing Home Residents Hospitalized Patients Military Personnel

9 Worldwide Burden HCV 115 Million HIV 40 Million Liver disease (largely due to HCV) is 2nd leading cause of death in HIV+ Sarpel, et al. Expert of Therapy Review Anti-Infective.

10 Best Estimates of Prevalence of HCV Co- Infection in Four Population Samples 2.4% 4% Platt L, et al. Lancett Infect Dis Feb % 82.4% Risk of HCV infection 5-8 times higher across all patient groups in HIV+ compared to HIV- individuals

11 The Longer the Duration of IVDU, the Higher the Risk of HCV Infection % Prevalence HCV Pre-1995 Post Years Hagan, et al. Am J Epidemiol

12 Total Hepatitis C by Age, Sex, and Year, New York (Excluding NYC) Female Male Female Male Female Male Female Male Slide courtesy of NYS DOH Bureau of Viral Hepatitis.

13 Increases in HCV Infection Related to Injection Drug Use Among Persons Age 30 Years Kentucky, Tennessee, Virginia, and West Virginia, No. of Cases per 100,000 Population Nonurban Urban Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. Vol. 64, No May 8.

14 New HCV in the US: Epidemic Among Young Heroin Users (< 30 y/o) Kentucky, Virginia, West Virginia, Tennessee Injection drug use 30 yrs drug use White Non-urban Injection 30 yrs White Non-urban Regional doubling of first time heroin users MMWR 2015 Suryaprasad AG, Clin Infect Dis 2014:15;59: of 4 had history of prescription opioid abuse

15 HCV/HIV Co-Infection Outbreak in Indiana 92% co-infected with HCV

16 Co-factors for a Perfect Storm Multigenerational injection drug use (IDU) No access to prevention (PEP, PrEP), drug treatment services, support groups, or needle exchange services Limited access to testing and treatment for HIV and HCV Limited knowledge among PWID regarding HIV and HCV transmission routes and efficacious treatment available for HIV and HCV (ART and DAAs)

17 HCV Co-Infection in HIV+ MSM Prevalence of HCV co-infection 6.4% Highest in North America 8 fold higher risk of coinfection vs. HIV- MSM Increased risk of sexual transmission HCV isolated in semen as well as rectum Platt L, et al. Lancet Infect Dis Feb 24; Foster AL, et al. Clin Infect Dis Feb 1.

18 Burden of HIV Co-Infection

19 Age-Adjusted Mortality Rates from HBV and HCV and HIV Infections Listed as Underlying Causes of Death in the United States Rate per 100,000 Population HCV mortality increasing HIV mortality stable Year Hepatitis B Hepatitis C HIV Extended from: KN Ly, et al. Ann Intern Med. 2012;156:271-8.

20 Annual Number of Deaths from HCV Exceeds All Other Nationally Notifiable Infectious Conditions Combined 30,000 25,000 Other nationally notifiable infectious conditions Number of Deaths 20,000 15,000 10,000 5,000 Hepatitis C Ly KN. Clin Infect Dis Years 60 infectious conditions other than HCV, as reported to CDC

21 HIV Adds a Decade to Fibrosis Scores Persons with HIV found to have liver fibrosis measurements equal to HIV patients who were 9.2 years older on average On average fibrosis scores kpa greater in HIV+ patients Low CD4 counts associated with higher liver fibrosis scores Kirk, et al. Ann Intern Med

22 Mechanisms of Accelerated Fibrosis in HIV/HCV Co-Infection Chen. Nat Rev Gastroenterol Hepatol

23 HIV-HCC Cooperative Italian-Spanish Group: HCC and HCV/HIV Coinfection Retrospective cohort ( ) HCC in HIV cohort (n=41) Most had stable HIV disease (30/31 deaths due to liver disease) HCV positive (88%) HCC in HIV-negative controls (n=701) CLIP database, HCV positive (75%) HCC diagnosis occurred at a younger age in HIV cohort 42 versus 64 years of age (P=0.002) HCC had a more aggressive course in the mostly HCV/HIV coinfected cohort Puoti M, et al. AIDS. 2004;18: Survival Rate HCC and Survival HIV Negative HIV Positive Time from HCC Diagnosis (Days)

24 HIV Treatment Does Not Completely Abrogate the Negative Effect ART decreases hepatic decompensation events: 0.72 ( ). Lo Re V. Ann Intern Med Anderson JP. CID 2004.

25 Screening and Linkage to Care

26 HIV/HCV Co-infection: Natural History Considerations Screening Test Individuals at High Risk that should be Screened Screening Guidelines (CDC) Anti-HCV antibody test followed by confirmatory HCV RNA One time screening of persons born between 1945 and 1965 without assessment of risk factors One time testing should be performed for any individual at high risk for HCV infection Any history of injection drug use Long term hemodialysis Recipient of blood or blood components or underwent organ transplant prior to July 1992 Recipient of clotting factor concentrates prior to 1987 *HIV infected individuals Children born to HCV infected mothers Unexplained liver disease including persistently elevated ALT Inmates of correctional facilities (AASLD) Receiving tattoo in an unregulated setting (AASLD) *Consider HCV RNA in immunocompromised individuals * Annual HCV testing is recommended for HIV-seropositive men who have unprotected sex with men.

27 HCV Testing Algorithm Immunocompromised

28 HCV Testing: Faster and Easier Than Before Rapid tests now available Test ONLY HCV Ab Still need to do a blood test to confirm HCV RNA New HCV Ab tests (blood) reflex to HCV RNA if Ab positive

29 Hepatitis C Care Cascade

30 HCV Care Cascade in HIV Patients Radwan et al. CROI % of PWID not screened In the first two years of DAA availability, treatment among HIV+ patients was restricted to older patients with advanced fibrosis and better HIV management High rates of SVR-12 (95.5%) for those treated Improved provider awareness of screening among HIV+ patients needed Efforts are needed to ensure the scaling up of DAA uptake, and DAA treatment uptake must be a priority

31 Treatment of HIV/HCV Co-Infection

32 Classes of Medications Used for Treatment NS3-4A Protease Inhibitors ( Previr )** NS5A Inhibitors ( Asvir ) NS5B Inhibitors: ( Buvir ) Nucleoside Analogues Non-Nucleoside Analogues Other Asunaprevir Daclatasvir Sofosbuvir Dasabuvir Ribavirin Glecaprevir Grazoprevir Paritaprevir Simeprevir Voxilaprevir Elbasvir Ledipasvir Ombitasvir Pibrentasvir Velpatasvir **CANNOT USE IN DECOMPENSATED DISEASE

33 Classes of Medications Used for Treatment Combination Therapies Trade Name Genotypes Glecaprevir/Pibrentasvir Mavyret 1,2,3,4,5,6 Grazeprevir/Elbasvir Zepatier 1,4 Sofosbuvir/Ledipasvir Harvoni 1, 4,5,6 Sofosbuvir/Velpatasvir Epclusa 1,2,3,4,5,6 Sofosbuvir/Velpatasvir/Voxilaprevir Vosevi 1,2,3,4,5,6

34 Integrated Overall SVR12 Analysis of HCV/HIV Co-infected Patients: 12 Weeks of Treatment % 95% 94% 93% 98% 100% LDV/SOF: ION-4 SOF/VEL: ASTRAL 5 PrOD:TURQOISE-1 EBR/GZR: C-EDGE SOF/DCV: ALLY-2 G/P:ENDURANCE-1 Naggie, et al. NEJM Wyles D, et al. NEJM Wyles D, et al. EASL Barcelona Sulkowski M, et al. JAMA. March Rockstroh JK, et al. Lancet HIV Zuezem S, et al. AASLD Boston. 2016

35 HCV Guidelines: Treatment Recommendations in HIV/HCV Co-infection Accessed 9/18

36 What About Drug-Drug Interactions?

37 Case #2 47 year old male presenting to your office for first visit. He is HIV+ and has been out of care for years. Work up reveals HIV VL 250,000 IU/mL (genotype with sensitive virus), CD4 60, HBV sag+, sab-, cab+, HCV Ab+, reflex RNA 11 million IU/mL. Further workup reveals patient with GT 1A and F2 disease by FibroScan.

38 What is the best treatment course for this patient? A) Initiate patient immediately on BIC/FTC/TAF and GLE/PIB for 8 weeks B)Start GLE/PIB for 8 weeks and once SVR is achieved start him on BIC/FTC/TAF C)Start patient on FTC/TAF with DRV/r, wait 4-8 weeks until he has some CD4 reconstitution then initiate GLE/PIB D)Start patient on BIC/FTC/TAF wait 4-8 weeks until he has some CD4 reconstitution then initiate GLE/PIB E)Start patient on BIC/FTC/TAF, wait until CD4 is 300 then start him on GLE/PIB

39 Special Considerations in Co-Infection When treatment for both HIV and HCV is indicated, the regimen should be selected with special consideration for potential drug-drug interactions (DDI) and overlapping toxicities Increased pill burden, increased toxicities (cirrhosis, CKD) CD4<200 cells/mm 3 initiate ARV and HCV therapy may be delayed until patient is stable on HIV treatment (CIII) ARV naïve patients with CD4>500 cells/mm 3 some clinicians may choose to defer ARV until HCV treatment is completed (CIII) Always check potential interactions! aidsinfo: AASLD/IDSA hcvguidelines: Liverpool:

40 Up to 70% May Have DAA-ARV Interactions Retrospective analysis of 125 coinfected patients prior to initiation of DAA 100% 90% DAA regimens included SMV/SOF, SOF/LDV, SOF/DCV and P/r/O/D ARVs included 80% 70% 60% 50% 40% 30% 7% 64% 54% 20% 47% 41% None Moderate Severe 81% TDF, 35% RAL, 16% EFV, 40% PI/r 20% 10% 0% 10% SOF/SMV SOF/LDV SOF/DCV P/r/O/D Langness J. 16th HIV and Hep Clin Pharm Workshop

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43 Summary Screen all populations at risk for HIV/HCV co-infection Co-infected patients have accelerated rates of fibrosis progression HIV/HCV co-infection is associated with higher rates of morbidity and mortality related to end-stage liver disease HIV/HCV co-infected persons should be treated and retreated the same as persons without HIV infection, after recognizing and managing interactions with antiretroviral medications