SHOULD EVERYONE WITH HCV/HIV COINFECTION BE TREATED NOW?

Transcription

1 SHOULD EVERYONE WITH HCV/HIV COINFECTION BE TREATED NOW? Kenneth E. Sherman, MD, PhD Gould Professor of Medicine Director, Division of Digestive Diseases University of Cincinnati College of Medicine

2 Disclosures Contracted Research (with institution): AbbVie, Anadys, BMS, Genentech, Gilead, Merck Advisory Board/Consulting (w/i 12 months): MedImmune, Merck DSMB and Endpoint adjudication Board: Janssen, Synteract

3 DO WE NEED TO TREAT NOW? Factors to Consider Risk of progression to a critical stage Drugs available now, versus later Patient preference Public Health Issues Treatment as Prevention Cost Lack of providers

4 Effect Of HAART on Liver Related Mortality In HCV/HIV Infected Patients Liver-related Mortality Cumulative Survival Patients with HAART Patients with ART Untreated Patients P= Observation Time (Days) Qurishi N et. al., Lancet, 2003.

5 Fibrosis Progression Rate by HIV Viral Load IshFU / yr 0,22 0,20 0,18 0,16 0,14 0,12 0,10 0,128 n = 382 P=0.29 0,136 0,128 P=0.015 P=0.52 P= ,122 0,151 P= ,122 P=0.005 P= , ,196 0,08 HIVnegative HIVpositive HIVnegative HIV RNA <400 HIV RNA 400+ HIV RNA <400 HIV RNA 400 to 99K HIV RNA 100K+ Bräu et al J Hepatol, 2006.

6 FIBROSIS PROGRESSION METAVIR HCV/HIV Coinfected Patient on Effective cart at Metavir U/year

7 FIBROSIS CHANGE Paired Sample Analysis Sherman et. al., JAIDS 2010

8 Rapid Progression of Liver Disease in HIV/HCV-Coinfected Patients Prospective study of fibrosis progression in 67 coinfected patients 2 biopsies; median time between biopsies was 2.84 years Patients With Mild Fibrosis ( F1) on First Biopsy Patients, % % 52% >25% of patients with mild fibrosis on initial biopsy had 2 stage progression in fibrosis score 14% 12% 6% 2% 4% 2% -1 No Change Change in Ishak Score From First to Second Biopsy Sulkowski M et al. AIDS, 2007

9 EXPANDED FIBROSIS PROGRESSION STUDY- JH 282 HCV/HIV without cirrhosis 69.2% Receiving cart at time of first bx and 69% over paired bx period Alcohol abuse 49.7% during pair biopsy period Paired Biopsy Performed Median Length cm Progression to 2 Stages (2 Metavir U) or More 39/282= 13.8% over Median Interval of 2.5 Years Predictors of rapid fibrosis Elevated BMI Diabetes Steatosis ALT or AST > 100 on >25% of Interval Tests but AST stronger predictor (?alcohol) Konerman MA et al. HEPATOLOGY 2014

10 DAAs AVAILABLE NOW Genotype 1 SVR Rate HCV HIV/HCV /64 28/38 419/521 42/53 206/260 13/15 15/23 7/10 9/17 16/28 260/292 17/19 17/25 87/114 BOC TPV SMV (Naive) SMV SMV (Partial) SMV P/R/SOFx12 SOF/R (Relapser) (Null) NOT DIRECT COMPARISON WITHIN TRIALS (provided by Susannah Naggie, MD) Poordad F et al, NEJM 2011; 364: vs. Sulkowski et al. Lancet Infect Dis 2013; 13(7): ; Jacobson I et al, NEJM 2011; 364: vs. Sulkowski et al. Ann Intern Med 2013; 159(2):;Antiviral Drugs Advisory Committee Meeting, FDA review, 10/24/13; C208, C216, C206, C212, HPC3007, Dieterich, 14 th European AIDS Conference, 2013; Lawitz et al. NEJM 2013 versus Torres-Rodriguez et al., IDSA 2013; Osinusi et al., JAMA 2013;310(8): versus Naggie et al. CROI 2014(PHOTON)

11 DAAs for HCV/HIV Telaprevir- Globally Available Boceprevir- Globally Available Simeprevir- US, Approved EU May 16, but not marketed until second half, under review in Australia Faldaprevir- Not available Sofosbuvir (and Ledipasvir)- Sofosbuvir available in U.S., Europe, under review in Australia, but Ledipasvir NOT available MK MK Not available Daclatasvir- No data ABT-450/r- No data ClinicalTrials.gov.

12 Sofosbuvir/Ledipsavir in HCV/HIV (ERADICATE) NIH Open Label Phase II N= 50 SOF/LDV qd x 12 weeks GT1 TN with or w/o cart Difficult Cohort G1a= 78% A-A= 84% F3= 26% BMI= SVR4 SVR12 0 No ARV cart Osinusi et al, EASL 2014

13 MK MK Riba (C- WORTHY) Phase II Open Label N= 59 HCV/HIV G1 Treatment Naïve F0-F2 Two Arms HCV/HIV MK mg + MK mg + RBV x 12 Wks MK mg + MK mg x 12 Wks %SVR4/ Merck Press Release 4/12/2014 Accessed 6/5/2014 on Web

14 PATIENT PREFERENCE N= 284 HCV-infected 5 Countries (UK, France, US, Germany, Spain Methodology: Choiceformat conjoint analysis to study trade-off Kauf TL et al, PATIENT 2012

15 TREATMENT AS PREVENTION Martin et al, HEPATOLOGY 2013

16 COST ISSUES In U.S K coinfected with HCV/HIV Genotype 1 Approx. 200,000 Treatment Cost (not including labs and physican fees) Sof/Riba x 24 Weeks= $172,000/case= 34 Billion Dollars At least 48,000 uncured and will need next gen therapy Sof/Sim x 12 Weeks (never tested)= $28 Billion Dollars US Direct Healthcare Expenditure= Approx $600 Billion If we treat everyone NOW, costs will exceed 5% of all U.S. Federal Healthcare expenditures

17 PROVIDER SHORTAGE Gastroenterologists in U.S. 10,390 but short 1,050 by 2020 just to meet colorectal Ca screening needs (Lewin Group Report, 2009) Includes dedicated Hepatologists Infectious Disease in U.S.?how many Shortage Predicted by 2020 due to less people entering the field (M. Tapper, Infectious Dis News accessed 6/6/2014) Primary Care Few interested or knowledgeable Project ECHO- 90 trained over multiyear period

18 Conclusion Treatment of all HIV infected with effective cart is appropriate TARGETED and SELECTIVE treatment with current agents is warranted New BETTER (more efficacious and possibly cheaper) therapies are coming NOW IS NOT THE TIME TO TREAT EVERYONE