CROI 2017 Report Back: Liver Disease and HIV Jennifer Price, MD, PhD Assistant Professor of Medicine, UCSF March 22, 2017

Outline Hepatitis C virus Hepatitis B virus “Real-world” efficacy of DAAs DAA uptake HCV epidemiology Hepatocellular carcinoma after SVR Hepatitis B virus Liver disease in HIV monoinfection (Late-phase investigational HCV regimens)

HCV: “Real-world” DAA efficacy in HIV/HCV coinfection GECCO Cohort Multicenter, 9 German sites Received various DAA regimens N=1505; 349 HIV/HCV (23%) Primarily men, genotype 1 29% with cirrhosis 19% on opioid substitution HIV/HCV vs HCV-mono: Fewer genotype 3 Higher baseline HCV RNA Less cirrhosis (22% vs 31%) 1096 1156 329 349 0% 20% 40% 60% 80% 100% HCV-mono HIV/HCV 95% 94% Regimens included PEG-RBV + SOF, SOF+ RBV, SOF + SIM, SOF + DAC +/- RBV, SOF /LDV, ProD +/- RBV Predictors of Non-SVR in HIV/HCV: Cirrhosis: OR 3.5 (95% CI 1.2 to 9.9) Boesecke #551

Predictors of Non-SVR in HIV/HCV: HCV: “Real-world” DAA efficacy in HIV/HCV coinfection GECCO Cohort Multicenter, 9 German sites Received various DAA regimens N=1505; 349 HIV/HCV (23%) Primarily men, genotype 1 29% with cirrhosis 19% on opioid substitution HIV/HCV vs HCV-mono: Fewer genotype 3 Higher baseline HCV RNA Less cirrhosis (22% vs 31%) 1096 1156 329 349 0% 20% 40% 60% 80% 100% HCV-mono HIV/HCV 95% 94% Regimens included PEG-RBV + SOF, SOF+ RBV, SOF + SIM, SOF + DAC +/- RBV, SOF /LDV, ProD +/- RBV Predictors of Non-SVR in HIV/HCV: Cirrhosis: OR 3.5 (95% CI 1.2 to 9.9) Take-Home Point: Similar “real-world” efficacy of DAA’s in HIV/HCV as HCV monoinfection Boesecke #551

Treatment Experienced HCV: “Real-world” DAA efficacy in HIV/HCV cirrhosis p=0.03 HIV/HCV + Cirrhosis Prospective,13 Spanish hospitals Cirrhosis by Fibroscan (LS >14.6 kPa), imaging, or clinical history N=170, received variety of regimens Primarily men, genotype 1 Majority treatment experienced Cirrhosis history 75% CTP A, 12% CTP B, 0.6% CTP C Median LS 21 kPa (IQR 16 to 34) 17% with prior decompensation 98% 89% 0% 20% 40% 60% 80% 100% 95% 94% 75 81 79 89 Treatment Experienced Naive Safety: 20 pts on RBV (16%) needed dose modification, mainly due to anemia 4 pts with decompensation (2.4%): -2 with encephalopathy, 2 with ascites Navarro #535

Treatment Experienced HCV: “Real-world” DAA efficacy in HIV/HCV cirrhosis p=0.03 HIV/HCV + Cirrhosis Prospective,13 Spanish hospitals Cirrhosis by Fibroscan (LS >14.6 kPa), imaging, or clinical history N=170, received variety of regimens Primarily men, genotype 1 Majority treatment experienced Cirrhosis history 75% CTP A, 12% CTP B, 0.6% CTP C Median LS 21 kPa (IQR 16 to 34) 17% with prior decompensation 98% 89% 0% 20% 40% 60% 80% 100% 95% 94% 75 81 79 89 Treatment Experienced Naive Safety: 20 pts on RBV (16%) needed dose modification, mainly due to anemia 4 pts with decompensation (2.4%): -2 with encephalopathy, 2 with ascites Take-Home Points: High efficacy and safety of DAA’s in HIV/HCV-coinfected pts with cirrhosis Though not a head-to-head comparison with HCV-monoinfected pts, results reinforce recommendations to treat both groups similarly Navarro #535

HCV: “Real-world” DAA efficacy in decompensated HIV/HCV cirrhosis Prospective HIV/HCV Madrid cohort Decompensated cirrhosis: h/o CTP B or C, decompensation event, or HCC N=170, treated Nov 2014-May 2016 Primarily men, genotype 1 51% CTP A, 43% CTP B, 6% CTP C 10% with h/o HCC 1 pt with prior liver transplant, 7 (5%) on transplant waiting list LDV/SOF most common; RBV 47% 95% NS 94% 65 75 49 62 4 9 CTP A CTP B CTP C Factors associated with DAA failure: Less failure in females: OR 0.29, p=0.04 More failure in CTP C: OR 9.43, p=0.004 Berenguer #534

HCV: “Real-world” DAA efficacy in decompensated HIV/HCV cirrhosis Prospective HIV/HCV Madrid cohort Decompensated cirrhosis: h/o CTP B or C, decompensation event, or HCC N=170, treated Nov 2014-May 2016 Primarily men, genotype 1 51% CTP A, 43% CTP B, 6% CTP C 10% with h/o HCC 1 pt with prior liver transplant, 7 (5%) on transplant waiting list LDV/SOF most common; RBV 47% 95% NS 94% 65 75 49 62 4 9 CTP A CTP B CTP C Factors associated with DAA failure: Less failure in females: OR 0.29, p=0.04 More failure in CTP C: OR 9.43, p=0.004 Take-Home Points: DAA efficacy decreases with more advanced disease Results are consistent with published reports in HCV-monoinfected patients with decompensated cirrhosis Berenguer #534

HCV: “Real-world” DAA efficacy in PWID co-located within needle syringe program 2 prospective pilot programs in NYC Eligible if ≥18 y/o, injected drugs within past 30 days, not decompensated HCV treatment co-located within a needle exchange facility 26 pts started on treatment: 92% men, 46% homeless None with HIV 54% G1, 23% with ≥F3 fibrosis All Medicaid active or eligible 58% on opioid substitution Injecting for median 19 years Eckhardt #554

HCV: “Real-world” DAA efficacy in PWID co-located within needle syringe program 95% 94% 1 d/c due to AE 1 d/c due to insurance lapse 2 treatment failures: both with EOT response but relapse with genotype not covered by original regimen ?unrecognized mixed genotype vs reinfection Eckhardt #554

HCV: “Real-world” DAA efficacy in PWID co-located within needle syringe program 95% 94% 1 d/c due to AE 1 d/c due to insurance lapse Take-Home Points: Effective method to treat PWID and can achieve high SVR Potential unrecognized mixed-genotype infection may complicate HCV treatment (perhaps less so with pan-genotypic regimens) Risk of reinfection in this population and impact of treatment as prevention need further investigation 2 treatment failures: both with EOT response but relapse with genotype not covered by original regimen ?unrecognized mixed genotype vs reinfection Both relapses were retreated and cured Eckhardt #554

HCV: “Real-world” DAA efficacy in homeless/marginally housed adults Boston Health Care for the Homeless Program Community health center with >60 locations in greater Boston area Began treating homeless and marginally housed (HMH) adults with oral DAAs in 2014: Included pts treated Feb 2014-Aug 2015 Barocas #557

HCV: “Real-world” DAA efficacy in homeless/marginally housed adults Boston Health Care for the Homeless Program Community health center with >60 locations in greater Boston area Began treating homeless and marginally housed (HMH) adults with oral DAAs in 2014: Included pts treated Feb 2014-Aug 2015 97% SVR (62/64) 7 pts reported missing ≥4 doses 2 failures cirrhotic (G2, G1) Barocas #557

HCV: “Real-world” DAA efficacy in homeless/marginally housed adults Boston Health Care for the Homeless Program Community health center with >60 locations in greater Boston area Began treating homeless and marginally housed (HMH) adults with oral DAAs in 2014: Included pts treated Feb 2014-Aug 2015 97% SVR (62/64) 7 pts reported missing ≥4 doses 2 failures cirrhotic (G2, G1) Take-Home Points: Despite perceived barriers to HCV treatment among homeless and marginally housed adults, treatment response rates can be high Larger studies are needed to determine factors associated with treatment success in this group Barocas #557

HCV: DAA uptake at single center in U.S. (Duke Health System) Retrospective cohort of DAA uptake among HCV-mono infected (n=9245) and HIV/HCV-coinfected (n=715) pts in Duke Health System from 2011 to 2015 HCV-mono HIV/HCV p-value Treatment uptake DAA +PEG-IFN/RBV 2% 1% 0.06 All oral DAA 10% 16% 0.001 Total treated 12% 17% Retrospective cohort of DAA uptake among HCV-infected pts in Duke Health System Collins #552

HCV: DAA uptake at single center in U.S. (Duke Health System) Retrospective cohort of DAA uptake among HCV-mono infected (n=9245) and HIV/HCV-coinfected (n=715) pts in Duke Health System from 2011 to 2015 HCV-mono HIV/HCV p-value Treatment uptake DAA +PEG-IFN/RBV 2% 1% 0.06 All oral DAA 10% 16% 0.001 Total treated 12% 17% Retrospective cohort of DAA uptake among HCV-infected pts in Duke Health System Collins #552

HCV: DAA uptake at single center in U.S. (Duke Health System) Retrospective cohort of DAA uptake among HCV-mono infected (n=9245) and HIV/HCV-coinfected (n=715) pts in Duke Health System from 2011 to 2015 HCV-mono HIV/HCV p-value Treatment uptake DAA +PEG-IFN/RBV 2% 1% 0.06 All oral DAA 10% 16% 0.001 Total treated 12% 17% Retrospective cohort of DAA uptake among HCV-infected pts in Duke Health System BREAK Take-Home Point: Treatment uptake in HCV-infected patients improved dramatically in the all-oral DAA era, especially among the HIV/HCV-coinfected. Collins #552

HCV: Epidemiology- HCV Prevalence in HIV- and HIV+ MSM Amsterdam PrEP project 375 HIV- MSM enrolled 18 anti-HCV+ or HCV RNA+ (4.8%) 15 with HCV RNA+ (83%) 73% GT1a Factors associated with HCV+ Younger age (median 33 vs 40 yrs) STI in prior 6 months (61% vs 35%) #receptive condomless anal sex in prior 3 months (median 14 vs 3) IDU in prior 3 months (24% vs 3%) Swiss HIV Cohort Study ~75% of HIV+ MSM in Switzerland Prevalent HCV: 178/3722 (4.8%) Known HCV: 147/178 (83%) Incident HCV: 31/178 (17%) No prior +HCV test in SHCS database 6 with non-reactive anti-HCV (21%) Factors associated with HCV+ Younger age (median 47 vs 50) Previous syphilis (67% vs 43%) Condomless sex with occasional partners (49% vs 27%) IDU (60% vs 30%) Non-injecting drug use (67% vs 43%) Swiss HIV Cohort Study HCV RNA testing 10/2015-5/2016 Hoornenborg #519 Braun #521

HCV: Epidemiology- HCV Prevalence in HIV- and HIV+ MSM Amsterdam PrEP project 375 HIV- MSM enrolled 18 anti-HCV+ or HCV RNA+ (4.8%) 15 with HCV RNA+ (83%) 73% GT1a Factors associated with HCV+ Younger age (median 33 vs 40 yrs) STI in prior 6 months (61% vs 35%) #receptive condomless anal sex in prior 3 months (median 14 vs 3) IDU in prior 3 months (24% vs 3%) Swiss HIV Cohort Study ~75% of HIV+ MSM in Switzerland Prevalent HCV: 178/3722 (4.8%) Known HCV: 147/178 (83%) Incident HCV: 31/178 (17%) No prior +HCV test in SHCS database 6 with non-reactive anti-HCV (21%) Factors associated with HCV+ Younger age (median 47 vs 50) Previous syphilis (67% vs 43%) Condomless sex with occasional partners (49% vs 27%) IDU (60% vs 30%) Non-injecting drug us (67% vs 43%) Take-Home Points: High prevalence of HCV in MSM (~5%) HCV associated with younger age, higher risk sexual behavior, drug use, and STI history Routine HCV testing should be offered to HIV+ MSM and HIV- MSM at high risk for HIV, especially those enrolling in PrEP programs Swiss HIV Cohort Study HCV RNA testing 10/2015-5/2016 Hoornenborg #519 Braun #521

HCV: Epidemiology- Incident HCV and Reinfection after SVR among HIV+ MSM Owen clinic, San Diego Incidence: HIV+ MSM with baseline negative anti-HCV between 2000-2015 HCV testing by end of 2015 Incident HCV: 149 cases 1.19 per 100 PY Higher in meth and/or IDU use Reinfection: HIV/HCV who underwent HCV tx 2006-2014 Reinfection: 3/43 2.89 per 100 PY Increasing HCV primary incidence among HCV+ MSM in San Diego test for trend p=0.003 Largest HIV clinic in San Diego Chaillon #134

HCV: Epidemiology- Incident HCV and Reinfection after SVR among HIV+ MSM Owen clinic, San Diego Incidence: HIV+ MSM with baseline negative anti-HCV between 2000-2015 HCV testing by end of 2015 Incident HCV: 149 cases 1.19 per 100 PY Higher in meth and/or IDU use Reinfection: HIV/HCV who underwent HCV tx 2006-2014 Reinfection: 3/43 2.89 per 100 PY Increasing HCV primary incidence among HCV+ MSM in San Diego test for trend p=0.003 Largest HIV clinic in San Diego; ~2400 HCV- men at baseline Take-Home Points: High and increasing HCV incidence among HIV+ MSM Elevated HCV reinfection risk among HIV+ MSM Chaillon #134

HCV: Epidemiology- decline in acute HCV in HIV+MSM after DAA roll out in Netherlands Unrestricted DAA access in HIV/HCV in Nov 2015 led to rapid uptake in treatment (76% cure in HIV+MSM) Pts with acute HCV have also been treated in 2 clinical trials Evaluated temporal changes in new HCV infections coinciding with increased DAA access Acute HCV defined as: HCV RNA+ in presence of negative HCV test in past 12 months HCV RNA+ in combination with new rise in ALT, negative test at any time in the past, and no other possible explanation Incident HCV among HIV+ MSM: 2014: 1.1% per year 2016: 0.55% per year Other STI’s: 41% increase in syphilis diagnoses from early 2015 to 2016 May 2016 January 2017 25% of the acutes were reinfecftions IRR 0.49 (95% CI 0.34 to 0.69) Boerekamps #137LB

HCV: Epidemiology- decline in acute HCV in HIV+MSM after DAA roll out in Netherlands Unrestricted DAA access in HIV/HCV in Nov 2015 led to rapid uptake in treatment (76% cure in HIV+MSM) Pts with acute HCV have also been treated in 2 clinical trials Evaluated temporal changes in new HCV infections coinciding with increased DAA access Acute HCV defined as: HCV RNA+ in presence of negative HCV test in past 12 months HCV RNA+ in combination with new rise in ALT, negative test at any time in the past, and no other possible explanation Incident HCV among HIV+ MSM: 2014: 1.1% per year 2016: 0.55% per year Other STI’s: 41% increase in syphilis diagnoses from early 2015 to 2016 May 2016 January 2017 Acute HCV defined as: HCV RNA+ in presence of negative HCV test in past 12 months HCV RNA+ in combination with new ALT rise, documented negative hCV test at any time in the past, and no other possible explanation Take-Home Points: Acute HCV in HIV+ MSM dropped in 2016 for the first time in a decade, coinciding with unrestricted DAA access Supports the concept of treatment as prevention IRR 0.49 (95% CI 0.34 to 0.69) Boerekamps #137LB

HCV: HCC after SVR in HIV/HCV Reports of HCC risk after SVR have been conflicting GEHEP-002 Cohort HCC cases diagnosed in HIV/HCV pts from 32 centers from Spain Analyzed 4 time periods: ≤ 2001: non-pegylated IFN 2002-2011: PEG-IFN + RBV 2012-Oct 2014: DAA + PEG-IFN Oct 2014-2016: IFN-free DAA 3 different analyses: 1) Proportion of HCC cases after SVR and change in proportion over time 2) Frequency of HCC after SVR in cirrhotics in each period 3) Incidence of HCC recurrence after SVR in pts with previous HCC treated with curative therapies and no ultrasound evidence of HCC prior to HCV tx Merchante #139

HCV: HCC after SVR in HIV/HCV 1) Proportion of post-SVR HCC cases 2) Frequency of post-SVR HCC in cirrhosis 3) HCC recurrence after HCV treatment Merchante #139

HCV: HCC after SVR in HIV/HCV 1) Proportion of post-SVR HCC cases 2) Frequency of post-SVR in cirrhosis 3) HCC recurrence after HCV treatment Take-Home Points: Proportion of HCC cases diagnosed in HIV/HCV pts after SVR increased in parallel with IFN-free DAAs This may be in part because DAAs allow treatment and cure in pts with advanced liver disease No evidence for increased HCC incidence with DAA use in current cohort Merchante #139

HBV: Increased HBV seroconversion under long-term HBV active therapy in HIV/HBV Background Data on HBsAg loss in HIV/HBV-coinfected pts are scarce Methods: retrospective cohort 2 German HIV care centers Results: 95 patients included Median 40 years, 78% male, median CD4 270 43% TDF and/or 3TC as 1st line ART, 54% HBeAg+, 95% HBV DNA+ Median follow-up 107 months (IQR 76-144) HBsAg loss in 14/95 patients (16%) Median time to HBsAg loss 35 months (IQR 18-49) 80% developed HBsAb No correlation with gender, age, country of origin, CDC stage, CD4 count, CD4 gain, HBeAg, receipt of TDF or TDF/3TC, or ART class (published rates in HBV-monoinfection 4.5% over 96 wks) Boesecke #580

HBV: Increased HBV seroconversion under long-term HBV active therapy in HIV/HBV Background Data on HBsAg loss in HIV/HBV-coinfected pts are scarce Methods: retrospective cohort 2 German HIV care centers Results: 95 patients included Median 40 years, 78% male, median CD4 270 43% TDF and/or 3TC as 1st line ART, 54% HBeAg+, 95% HBV DNA+ Median follow-up 107 months (IQR 76-144) HBsAg loss in 14/95 patients (16%) Median time to HBsAg loss 35 months (IQR 18-49) 80% developed HBsAb No correlation with gender, age, country of origin, CDC stage, CD4 count, CD4 gain, HBeAg, receipt of TDF or TDF/3TC, or ART class Take-Home Points: HBsAg loss occurs at a much higher rate in HIV/HBV-coinfected patients after years on active HBV therapy (published seroconversion rates in TDF trials in HBV-monoinfection 4.5% over 96 weeks) May be due to immune reconstitution, although predictors of seroconversion are unclear (published rates in HBV-monoinfection 4.5% over 96 wks) Boesecke #580

Liver disease in HIV monoinfection: Steatosis and fibrosis ECHAM Cohort 7 centers in Europe Persistently ↑ transaminases +/- metabolic syndrome or lipodystrophy No HCV, HBV, heavy EtOH 402 pts enrolled 2014-2015 Median age 55, 85% male 43% overweight, 18% obese 48% elevated glucose or on anti-DM treatment 97% undetectable HIV VL 64% with hepatic steatosis Fibrosis on Fibroscan® or Fibrotest® MRI strongly correlated with histologic steatosis Fibroscan and non-invasive markers (Fibrotest, Steatotest, NashTest) correlated poorly with histology 140 biopsy eligible, biopsy completed in 50 (35%), histology available in 49 NAFLD 76% F0/F1 Fibrosis 67% Simple steatosis 29% F2-F4 Fibrosis 33% NASH 47% F2 15% F3 13% F4 (cirrhosis) 4% Lemoine #703

Liver disease in HIV monoinfection: Steatosis and fibrosis ECHAM Cohort 7 centers in Europe Persistently ↑ transaminases +/- metabolic syndrome or lipodystrophy No HCV, HBV, heavy EtOH 402 pts enrolled 2014-2015 Median age 55, 85% male 43% overweight, 18% obese 48% elevated glucose or on anti-DM treatment 97% undetectable HIV VL 64% with hepatic steatosis Fibrosis on Fibroscan® or Fibrotest® MRI strongly correlated with histologic steatosis Fibroscan and non-invasive markers (Fibrotest, Steatotest, NashTest) correlated poorly with histology Take-Home Points: NAFLD is most common cause of liver disease in HIV-monoinfected individuals without heavy alcohol use Abnormal histology is common in individuals selected for biopsy We need better non-invasive methods/algorithms to determine who is at highest risk of unfavorable histology and disease progression 140 biopsy eligible, biopsy completed in 50 (35%), histology available in 49 NAFLD 76% F0/F1 Fibrosis 67% Simple steatosis 29% F2-F4 Fibrosis 33% NASH 47% F2 15% F3 13% F4 (cirrhosis) 4% Lemoine #703

Summary “Real-world” efficacy of HCV DAAs Efficacy appears to be similar to HCV-monoinfected pts Pts with advanced cirrhosis have lower SVR rates High SVR rates are achievable in marginalized/vulnerable populations HCV DAA uptake & Epidemiology Rapid update of all-oral DAA treatment in HIV/HCV pts HIV+ MSM are at increased risk of incident HCV and reinfection after SVR Optimal strategies for risk reduction are needed for HCV elimination

Summary HBV HIV monoinfection Higher than expected HBV seroconversion rates observed in HIV/HBV-coinfected pts after years of ART with HBV activity. HIV monoinfection Nonalcoholic fatty liver disease is the most common cause of liver disease in the absence of heavy alcohol use. Non-invasive methods to estimate fibrosis are sub-optimal Whether HIV increases the risk of fibrosis progression is unknown

Late-Phase Investigational HCV Regimens: What They Offer Key Features Sofosbuvir/velpatasvir/voxilaprevir Once-daily FDCs Pangenotypic High SVR rates in DAA-experienced pts (and other populations) Glecaprevir/pibrentasvir Grazoprevir/ruzasvir/ MK-3682 AL-335 + odalasvir + simeprevir Once daily MK-3682: NSB5 polymerase nucleotide inhibitor RZR: ruzasvir; NS5A inhibitor Slide credit: clinicaloptions.com

Late-Phase Investigational HCV Regimens MK-3682/GZR/RZR +-/RBV SOF/VEL/VOX GLE/PIB* 100% 100% 100% 97% 100% 99% 99% 96% 96% 98% 99% 100% 95% 95% 97% 97% 98% 80% 80% 80% No dose adjustments required when GLE/PIB is coadministered with elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide, abacavir, dolutegravir, or lamivudine Kosloski #413 60% 60% 60% 40% 40% 40% MK-3682: NSB5 polymerase nucleotide inhibitor RZR: ruzasvir; NS5A inhibitor Can’t use PI with GLE/PIB; genvoya and triumeq 20% 20% 20% 253 263 476 501 106 110 177 182 331 332 195 196 120 121 59 62 102 104 87 88 60 62 155 159 43 44 30 0% 0% 0% NS5A failure, GT1-6, 12wks G3 cirrhosis, 8wks GT1 +/- HIV no cirrhosis GT4-6 no cirrhosis GT1-6 CKD GT1 12 wks GT3 12 wks GT1 DAA failure 24 wks DAA-naïve GT1-6, 8wks DAA-Exp’d, NS5A naïve GT1-6, 12wks G2 no cirrhosis G3 cirrhosis GT2 12 wks GT1 DAA failure, 16 wks+RBV *12 wk results shown

HCV: DAA uptake in large French cohort DatAIDS Cohort ~25% of HIV+ pts in France All HIV/HCV-coinfected pts followed 2012-2015 were included 5,001 HIV/HCV-coinfected pts included 72% men, 51% IVDU was HIV RF, 18% MSM 41% ≥F3 fibrosis Treatment initiation rate Cotte #550

HCV: DAA uptake in large French cohort Cotte #550

HCV: DAA uptake in large French cohort Take-Home Points: HCV treatment significantly increased in HIV/HCV-coinfected pts in France from 2012-2015, leading to cure in over half of patients Prevalence of HCV among HIV+ pts is expected to continue to decrease with ongoing rapid DAA uptake Cotte #550

HCV: Epidemiology- Incident HCV and Reinfection after SVR DatAIDS Cohort ~25% of HIV+ pts in France 17,890 HCV- pts followed from 2012 to 2015 Incident HCV: 146 cases 98% male, 87% MSM 39% GT1a, 53% GT4 Incidence rate increased from 0.35 to 0.69 per 100 person-years in MSM Median incidence rate 0.08 per 100 PY in non-MSM 1st infection Reinfection Reinfection: 45 pts (2 with 2nd reinfection) 93% male, 71% MSM 47% GT1a, 38% GT4 Median reinfection rate 2.56 per 100 PY in MSM, 0.22 per 100 PY in non-MSM #Treated 2012-2015: 1457 Cotte #550

HCV: Epidemiology- Incident HCV and Reinfection after SVR DatAIDS Cohort ~25% of HIV+ pts in France 17,890 HCV- pts followed from 2012 to 2015 Incident HCV: 146 cases 98% male, 87% MSM 39% GT1a, 53% GT4 Incidence rate increased from 0.35 to 0.69 per 100 person-years in MSM Median incidence rate 0.08 per 100 PY in non-MSM 1st infection Reinfection Take-Home Points: Among HIV+ pts in France, new HCV infections and reinfections after SVR occurred mostly in MSM Strengthened information and preventive measures are needed among HIV+ MSM Reinfection: 45 pts (2 with 2nd reinfection) 93% male, 71% MSM 47% GT1a, 38% GT4 Median reinfection rate 2.56 per 100 PY in MSM, 0.22 per 100 PY in non-MSM Cotte #550

HCV: Epidemiology- Reinfection after SVR in GECCO Cohort Multicenter, 9 German sites Treated since February 2014 1,417 with SVR4 24 with reinfection (1.7%) Reinfection occurred within median 41 wks (IQR 25-67) after EOT response Among 24 reinfections: 4 HIV-, all IDU 20 HIV+, 19/20 MSM (5 with occasional IDU) 11% reinfection in MSM after median 45 wks 1% reinfection in IVDU after median 40 wks Largest HIV clinic in San Diego Ingiliz #567

HCV: Epidemiology- Reinfection after SVR in GECCO Cohort Multicenter, 9 German sites Treated since February 2014 1,417 with SVR4 24 with reinfection (1.7%) Reinfection occurred within median 41 wks (IQR 25-67) after EOT response Among 24 reinfections: 4 HIV-, all IDU 20 HIV+, 19/20 MSM (5 with occasional IDU) 11% reinfection in MSM after median 45 wks 1% reinfection in IVDU after median 40 wks Largest HIV clinic in San Diego Take-Home Point: HIV+ MSM have increased risk of reinfection after SVR Ingiliz #567

HCV: DAA uptake after unrestricted access in the Netherlands ATHENA Cohort: HIV/HCV-coinfected pts in Netherlands Nationwide data from care of 98% of HIV-infected patients in the Netherlands DAAs unrestricted in HIV/HCV in Nov 2015 Cohort analyzed after 6 months (May 2016) and again Jan 2017 22,042 HIV+ patients in ATHENA cohort 2422 HCV RNA +  1420 alive and in care May 2016 included in study after excluding those who spontaneously cleared or lacked HCV RNA+ confirmation 89% male, 68% MSM, 61% genotype 1, 32% severe liver disease 94% on cART, 95% with HIV VL <100 c/ml Boerekamps #136

HCV: DAA uptake after unrestricted access in the Netherlands Boerekamps #136

HCV: DAA uptake after unrestricted access in the Netherlands 65% cured/expected to be cured in near future 70% cured/expected to be cured in near future May 2016 January 2017 Boerekamps #136

HCV: DAA uptake after unrestricted access in the Netherlands 65% cured/expected to be cured in near future 70% cured/expected to be cured in near future May 2016 January 2017 Take-Home Points: Rapid DAA update in Dutch HIV/HCV-coinfected patients has led to 70% cured/expected to be cured in the near future 76% of coinfected MSM cured/expected to be cured Patients still in need of HCV treatment: females, ex-IVDU, uncontrolled HIV MSM may be prioritized in these clinics Boerekamps #136

Liver disease in HIV monoinfection: Fibrosis progression Change in liver stiffness measurements Used Fibroscan® to assess ∆LS in HIV-monoinfected adults Study population(n=44) Stable ART ↑AST or ALT for >6 months No chronic viral hepatitis or ongoing EtOH abuse Baseline liver biopsy 31 (70%) had NAFLD 24 (55%) with NASH, including 10 with F3-F4 fibrosis 11 (25%) had non-specific changes 2 (5%) had fibrosis without NAFLD Higher total cholesterol and LDL associated with fibrosis progression No other factors associated with ∆LS 15 had repeat biopsy, median 4 years after baseline (range 2-8 years): fibrosis progression in 4 (26%) 75% obese, 14% WITH dm, MOST MEN (89%), AGE 50, tg 196; 24% progressed; median 4.8 Krakora #525

Liver disease in HIV monoinfection: Fibrosis progression Change in liver stiffness measurements Used Fibroscan® to assess ∆LS in HIV-monoinfected adults Study population(n=44) Stable ART ↑AST or ALT for >6 months No chronic viral hepatitis or ongoing EtOH abuse Baseline liver biopsy 31 (70%) had NAFLD 24 (55%) with NASH, including 10 with F3-F4 fibrosis 11 (25%) had non-specific changes 2 (5%) had fibrosis without NAFLD Take-Home Points: Fibrosis progression is common in HIV-monoinfected adults with elevated AST or ALT on ART Fibroscan may have utility in following at-risk patients longitudinally, but further validation studies are needed Whether the natural history of NAFLD is altered by HIV unknown and warrants further investigation Higher total cholesterol and LDL associated with fibrosis progression No other factors associated with ∆LS 15 had repeat biopsy, median 4 years after baseline (range 2-8 years): fibrosis progression in 4 (26%) 75% obese, 14% WITH dm, MOST MEN (89%), AGE 50, tg 196 Krakora #525