HIV/hepatitis co-infection. Christoph Boesecke Department of Medicine I University Hospital Bonn Germany
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1 HIV/hepatitis co-infection Christoph Boesecke Department of Medicine I University Hospital Bonn Germany
2 Clinical Management and Treatment of HBV and HCV Co-infection in HIVpositive Persons
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4 Hepatitis B Co-infection
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7 So far, so boring. Any HBV/HIV news? PR PR + TVR
8 THE place to go for exciting news: PR PR + TVR
9 THE place to go for exciting news: PR PR + TVR
10 HBV Seroconversion More Frequent in HIV Coinfection 2 German Centres Baseline and FU Parameters HBsAg Loss Median Age [Years] (IQR) N=95 40 (34-45) Male Sex [%] 78 Main HIV Transmission Risks [MSM/HP/Het; %] 43/24/12 CDC C3 [%] 25 TDF and/or 3TC as 1 st Line Art [%] Δ =16% Baseline Month 35 (Median) Median CD4T cells [/ul] (IQR) Median Follow- up [Months] (IQR) Median CD4T Cell Gain [/ul] (IQR) Median Time to HBsAg Loss [Months] (IQR) 270 ( ) 107 (76-144) 165 (3-315) 35 (18-49) HBsAg- loss in 16% (15/95) Anti- HBs in 80% (12/15) Anti- HBe in 27% (26/95) Boesecke C, et al. 24th CROI;; Seattle, WA;; February 13-16, Abst. 580.
11 Switching from TDF to TAF in HBV/HIV coinfection Phase 3b open label in Japan and North America 72 patients (96% on TDF) Switch from any cart to E/C/F/TAF HBsAg+, no cirrhosis, egfr >50mL/min No influence on HIV-RNA and HBV-DNA No change in egfr Gallant J JAIDS 2016
12 2 notes of caution TDF or TAF provide protection against HBV in vaccine non-responders Consider addition of TDF or TAF in HIV-patients with full HBV seroconversion and no HBV-active cart undergoing chemotherapy/immunosuppression PR PR + TVR
13 Hepatitis C Co-infection
14 A
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17 DDI: Glecaprevir & Pibrentasvir GT 1-6 PK-data in 24 HIV- healthy volunteers GLE 300mg + PIB 120mg qd ART: Genvoya or Triumeq Elvitegravir 1.36 ( ) 1.47 ( ) 1.71 ( ) Abacavir 0.96 ( ) 1.05 ( ) 1.31 ( ) Cobicistat 1.29 ( ) 1.42 ( ) 1.72 ( ) Dolutegravir 1.10 ( ) 1.13 ( ) 1.22 ( ) Emtricitabine Tenofovir Glecaprevir Pibrentasvir Cmax AUC24 C ( ) 1.12 ( ) 1.18 ( ) 1.04 ( ) 1.06 ( ) 1.25 ( ) 1.24 ( ) 1.57 ( ) 1.89 ( ) 2.50 ( ) 3.05 ( ) 4.58 ( ) Lamivudine Glecaprevir Pibrentasvir Cmax AUC24 C ( ) 1.03 ( ) 0.95 ( ) 0.74 ( ) 0.75 ( ) 0.82 ( ) 0.74 ( ) 0.72 ( ) 0.73 ( ) No dose adaptation recommended Kosloski M, et al. 24th CROI;; Seattle, WA;; February 13-16, Abst. 413.
18 Recent HCV/HIV rumours PR PR + TVR
19 From the 2nd exciting place on earth: PR PR + TVR
20 DAA cause HCC? Coinfection reduces SVR? PR PR + TVR
21 GEHEP 002 Spanish HCV/HIV Cohort: HCC after DAA therapy 319 HCV/HIV patients with HCC from 32 Spanish centres 45% pretreated HCC after median months after SVR No increased HCC recurrence rate after SVR 100% n HCC After SVR/Total n HCC 80% p <0.001* 60% 40% 20% 1 (16.70%) (9.90%) (9%) 13 (31.70%) 0% < Oct 2014 Oct Total HCC Cases N=6 N=161 N=111 N=41 Merchante N, et al. 24th CROI;; Seattle, WA;; February 13-16, Abst. 139.
22 Frequency of HCC Diagnosis After SVR in HIV/HCV Coinfected Patients with Cirrhosis 19 centers from the GEHEP- 002 cohort reported data of the number of HIV/HCV- coinfected patients with cirrhosis who achieved SVR in each period % N=1305 HIV/HCV cirrhotic with SVR before January IFN PEG- IFN + RBV DAA + PR DAA IFN free HCC after SVR No. with SVR Merchante N, et al. 24th CROI;; Seattle, WA;; February 13-16, Abst. 139.
23 DAA Really Similarly Effective in HIV Coinfection? SVR12 According to CD4 and Cirrhosis Status GECCO Cohort (9 German centres) n= mono-, 349 coinfected Liver cirrhosis 29% (31% vs. 22%) Overall-SVR 95%, 95% monoinfected, 94% coinfected SVR 12(%) CD4 350 CD4 <350 CD4 350 CD4 <350 Non- cirrhotic Cirrhotic SVR lower in pts. with CD4 <350/µl and liver cirrhosis Boesecke C, et al. 24th CROI;; Seattle, WA;; February 13-16, Abst. 551.
24 So, why do we still (need to) talk about HCV? PR PR + TVR
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26 Who receives DAA treatment? patients fromthe Canadian Coinfection Cohort 24% treated with DAA, SVR 91% 250 SVR rates per subgroup No HCV-infected % 89% 15%100% 13% 85% 44% 87% 30% 87% 0 Indigene Frauen IVDU MSM Andere Therapiewürdig Gen. DAA Therapie begonnen Sustained Virologic Response Non-Response Missing Saeed S et al CROI 2017 #553
27 1150 HCV-patients Buyers Clubs Worldwide SOF, DCV, LDV via Buyers Clubs in Australia, China, Russia, South- East-Asia F4 (cirrhosis) F3 Baseline Fibrosis F0 16% 26% 19% 10% 29% F1 % HCV RNA < 30 IU/mL 100% 80% 60% 40% 20% 0% 97% 100% SVR12 rates 96% 100% 100% GT1 GT2 GT3 GT4 GT5 & GT6 F2 (108/111) (9/9) (53/55) (2/2) (2/2) HCV Genotype Overall SVR12 currently 90% (454/503) Hill A et al CROI 2017 #569
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29 PR PR + TVR 1 viral breakthrough 2 non-responders in one case HCV protease inhibitor associated mutations were selected under TVR (V36M,155K). Antiviral Therapy 2017, in press
30 German GECCO Cohort: HCV-reinfections GECCO-Cohort (9 German centres) n= re-infections Re-infection rate: 11% (19/166) in MSM after median 45 weeks 1% (5/454) in IVDU after median 40 weeks Characteristics re-infected Reinfection n = 24 Median Age [years (IQR)] 49 (42 54,5) Male [n (%)] 24 (100) Mode of HCV transmission IVDU [n (%)] MSM [n (%)] MSM + IVDU [n (%)] 5 (21) 14 (58) 5 (21) HIV coinfection [n (%)] 20 (83) Median time to reinfection [weeks (IQR)] 41 (25 67) Previous HCV treatment SOF-PEG-RBV [n (%)] SOF/LDV [n (%)] PTV/r/OBV+/-DSV+/-RBV SOF/RBV SOF-DCV SIM-SOF 7 (29) 11 (46) 2 (9) 1 (5) 2 (9) 1 (5) Ingiliz P et al CROI 2017 #567
31 Swiss Cohort Routine PCR-based HCV Screening Study Flow Diagram 31 were diagnosed with acute HCV of whom 21% were anti- HCV- Ab negative of whom 2 showed normal liver enzymes MSM participating in the SCHCS N=4 257 MSM screened within Swiss HCVree Trial N=3 722 (87%) MSM with replicating HCV N=178 (4.8%) Genotype 1: 128 (72%) Genotype 2: 2 (1%) Genotype 3: 9 (5%) Genotype 4: 39 (22%) Incident HCV infection N=31 (17%) Known HCV infection N=147 (83%) Non- reactive anti- HCV N=6 (21%) Reactive anti- HCV N=22 (79%) Missing values N=3 Braun D, et al. 24th CROI;; Seattle, WA;; February 13-16, Abst. 521.
32 Dutch Athena Cohort Rapid and early treatment uptake of DAAs Since 11/2015 unrestricted access to DAA Early treatment initiation in n=736 70% cure - Jan 2017 Number of Patients HCV Infected Never treated Unsuccessfully treated with DAA Unsuccessfully treated with (PEG- )IFN +/- BOC or TVR Currently on treatment Treatment with DAA Treatment with (PEG- ) IFN +/- BOC or TVR Retained in care Ever treated Treatment completed SVR Boerekamps A, et al. 24th CROI;; Seattle, WA;; February 13-16, Abst. 136.
33 Dutch Acute HCV in HIV Study (DAHHS;; 8 Centres) Declining Acute HCV epidemic Due to DAA? 2014 A- HCVn=93 PYFU n= /1000PYFU (95% CI 9-14) 1.1% per year 2016 A- HCVn=49 PYFU n= /1000PYFU (95% CI 4-7) 0,55% per year IRR 0.49 (95% CI ) Jan- Dec /1000 Jan- Jun /1000 Jul- Dec /1000 BUT: 41% Increase in Syphilis Cases in 2016 vs Boerekamps A, et al. 24th CROI;; Seattle, WA;; February 13-16, Abst. 137LB.
34 A
35 DAAs in acute HCV 26 HIV-infected patients with acute HCV GT 1 or 4 HCV Ab/PCR negative in previous 6 months Patients, % SVR rate after 6 weeks SOF/LDV 85 SVR4 4 Virologic failures* 77 22/26 20/26 SVR12 4 Virologic failures* 2 Lost to follow-up 4x virologic failure: 1x re-infection (GT1a ->4d), 3x relapse high baseline HCV RNA, late treatment initiation Rockstroh JK et al CROI 2016 #154LB
36 Baseline HCV RNA and SVR SVR12 SVR4 Relapse Reinfection HCV RNA (log 10 IU/mL) SVR 100% in AHC mono-infection (n=20) Rockstroh JK et al CROI 2016 #154LB Deterding et al EASL 2016 #LB08
37 What happens after HCV cure? Meta-analysis of 32 studies ( patients) Risk of liver transplantation after 5 years HCV n=108 Mean FU 4.2 yrs HCV cirrhosis n=1046 Mean FU 7.7 yrs HCV infected Cirrhosis HIV/HCV SVR Non SVR HIV/HCV n=2039 Mean FU 4.9 yrs HCC risk after 5 years HCV n=12496 Mean FU 6.1 yrs 9.3 HCV cirrhosis n=4987 Mean FU 6.6 yrs HCV infected Cirrhosis HIV/HCV SVR Non SVR HIV/HCV n=2085 Mean FU 4.7 yrs Lacombe K CROI 2016 #560;; Simmons B et al Clin Infect Dis 2015
38 Beyond Hepatitis B & C More than 20 cases of acute hepatitis A virus infection have been reported in Berlin, Germany. First cases were reported in Nov Most infections have been reported in MSM in the age group 20 to 46. PR PR + TVR
39 Conclusions Switching from TDF to TAF appears to be safe and effective No evidence for an increased incidence of HCC with DAA use Patients with HIV/HCV coinfection and lower CD4- counts and cirrhosis show less favorable SVR rates Consider HCV-PCR for acute HCV diagnosis as HCV- Ab may still be negative Increased uptake of DAA therapy in acute and chronic HCV may help to decrease new HCV PR PR + TVR infections Pay attention to HAV/HBV vaccination
40 back-up PR PR + TVR
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