My HCV patient is co-infected with HIV: how to manage?

Transcription

1 EASL «White Nights of Hepatology 2016» My HCV patient is co-infected with HIV: how to manage? A.V. Кravchenko MD, Professor Russia AIDS Federal Center Central Research Institute of Epidemiology St.-Petersburg, June 2, 2016

2 The proportion of patients with HIV infection in the Russian Federation who have a diagnosis of chronic hepatitis C and / or B 50,00% 40,00% 30,00% 20,00% 10,00% 39,40% 40,90% 36,80% 36,80% 35,50% 34,90% 27,80% 0,00% % of the patients have a diagnosis of hepatitis C who are under medical supervision. In gg. from end-stage liver disease died patients with HIV infection in Russia. Chronic viral hepatitis treatment received 12.1% of the patients. А.V. Kravchenko et al., 5 ЕЕСААС, 2016, Abstract book, P According to the registration form 61

3 Distribution HIV-infected patients of HCV genotypes 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 58 55, ,4 41,4 Genotype 3 Genotype 2 Genotype 1 V.G. Kanestry, A.V. Kravchenko et al. Epidemiology and Infectious diseases, 2001; 1: A.V. Kravchenko et al. 4 Russian Congress of Infectious diseases, J. Infectious diseases,2012; Suppl.1 (10):

4 HCV/HIV Coinfection: Who to Treat? All HCV/HIV coinfected patients are candidates for HCV therapy For most HIV/HCV-coinfected patients, including those with cirrhosis, the benefits of ART outweigh concerns regarding drug-induced liver injury Although older antiretroviral drugs have been associated with higher rates of hepatotoxicity in patients with chronic HCV infection, newer antiretroviral agents currently in use appear to be less hepatotoxic Consider comorbid conditions that limit life expectancy or increase the risks associated with HCV therapy Recommended initial ART regimens for most HCV/HIVcoinfected patients are the same as those recommended for individuals without HCV infection HIV disease must be stable before initiating HCV therapy AASLD/IDSA. HCV Management (February 24, 2016). DHHS. Revision January 26, 2016.

5 Management of Persons with Chronic HCV/HIV Co-infection Chronic HCV/HIV Perform FibroScan and/or serum marker and/or liver biopsy F0/F1 F2-F4 HCV treatment can be Considered HCV treatment Is Recommended Guidelines of European AIDS Clinical Society, Version 8.0. October 2015

6 Proportion Free From Event (%) SVR Associated With Decreased Morbidity, Mortality in HIV/HCV Pts Retrospective analysis of 695 HIV/HCV-coinfected pts treated with IFN/RBV between 1/2000-1/2008 in 19 centers in Spain Median follow-up (IQR): No SVR: 59.3 mos ( ) SVR: 59.5 mos ( ) SVR significantly associated with decreased overall mortality and secondary liver outcomes SVR No SVR P = P =.024 Overall mortality Liver-related mortality P = P <.001 Liver decompensation Liver-related events Follow-up (Mos) Berenguer J, et al. ICAAC Abstract H Reproduced with permission.

7 Proposed Optimal Duration of Dual HCV Therapy in Persons with Chronic HCV/HIV Co-infection Not Eligible for Triple Therapy Including DAAs against HCV Guidelines of European AIDS Clinical Society, Version 8.0. October 2015

8 Rate SVR (%) in HCV/HIV Co-infection patients by Genotype HCV (mitt-analisys) Genotypes 2/3 62,16 77,78 Genotype 1 36,36 52,9 All genotypes 50 65, % PegIFN CePegIFN F.I. Nagimova et al. Infectious diseases, 2016; 1(14): 5-13.

9 80 SVR according to rs genotype IL28 in HIV/HCV co-infected patients with G1 HCV (mitt-analisys) 75% ,8% 55,6% ,22% 30% 25% 10 0 CePegIFN PegIFN С/С С/Т Т/Т F.I. Nagimova et al. Infectious diseases, 2016; 1(14): 5-13.

10 SVR24, % Naïve Patients with HCV genotype G1, that can be successfully treated with dual therapy The distribution of predictors in accordance with the pre-treatment and RVR RVR IL28B non-cc RVR IL28B CC No RVR RNA HCV IU/ml RNA HCV < IU/ml RNA HCV IU/ml RNA HCV < IU/ml Patients therapy with PegIFN alpha 2a or alpha 2b + RBV. Andriulli A, et al. J Hepatol 2014; 60: 16 21

11 Multiple Classes of Direct-Acting Anti-НСV Agents NS3 Protease Inhibitors Telaprevir Boceprevir Simeprevir Asunaprevir Paritaprevir Narlaprevir* Danoprevir* Sovaprevir* Grazoprevir* NS5A Replication Complex Inhibitors Daclatasvir Ledipasvir* Ombitasvir Elbasvir* Velpatasvir* NS5B-Polymerase NUC Inhibitors Non-NUC Inhibitors Sofosbuvir Dasabuvir Beclabuvir* Lomibuvir* Setrobuvir* -previr -asvir -buvir * Non registration in Russia

12 HCV Treatment Options in HIV/HCV Co-infected Persons Guidelines of European AIDS Clinical Society, Version 8.0. October 2015

13 HCV Treatment Options in HIV/HCV Co-infected Persons Guidelines of European AIDS Clinical Society, Version 8.0. October 2015

14 SVR12 (%) Study 212: SVR12 rates in HIV/HCV coinfected patients G1 treated with SMV/PR p< SMV/PR Historic PR-only control p< * /53 51/176 16/28 2/37 Naïves 5 Non-responders *From PEGASYS USPI, co-infected patients; from INCIVEK USPI, mono-infected patients Dieterich D, et al. EACS Abstract LBPS9/5

15 Patients (%) TURQUOISE-I: SVR12 rates Ombitasvir/ Paritaprevir/r + Dasabuvir + RBV in HCV Genotype 1 With HIV Co-infection ,5 90,6 29/31 29/32 12 weeks 24 weeks The SVR12 rates in the 12- and 24- week arms was 93,5% (29/31) and 90,6% 929/32), respectively The SVR12 was 91.1% in patients with GT1a and 100% - GT1b Safety No treatment-emergent serious adverse events or discontinuations due to adverse events RBV dose reduction (n=6, all achieved SVR) Most common adverse events Fatigue, insomnia, nausea, headache Wyles D et al. Presented at the 65th Annual Meeting of the AASLD, November 7-11, 2014, Boston, Massachusetts. Poster

16 SVR12 (%) TURQUOISE-I: Efficacy (ITT) and Resistance Results n/n = 12 wks (n = 31) 24 wks (n = 32) * 29/ 31 29/ 32 15/ 16 12/ 12 Overall Atazanavir Raltegravir *2 pts in 24-wk arm had HCV viremia recurrence suspected to be caused by HCV reinfection. Eron JJ, et al. Glasgow HIV Abstract O222. Reproduced with permission. 14/ 15 17/ 20 VF with RAVs in all 3 HCV target genes occurred in 2 pts with genotype 1a HCV, previous null response to pegifn/rbv, and cirrhosis VF (posttreatment) without RAVs occurred in 2 HCV treatment-naive pts with genotype 1a HCV Genetic analysis strongly supported HCV reinfection with different isolate Both pts MSM who reported highrisk sexual practices posttreatment

17 SVR12, % ALLY-2: Virologic Outcomes With SOF + DCV in HIV/HCV-Coinfected Pts High SVR12 rates with 12 wks SOF + DCV n/n = 0 Large decline in SVR rate with shortening to 8 wks 96 80/ Wk GT Overall / 43/ 98/ 38/ 51/ Wk 12-Wk 12-Wk 8-Wk 12-Wk Naive Exp d Naive Exp d In 12-wk groups analyzed by GT, 100% with SVR12 except GT1a GT1a naive: 96%; exp d: 97% Similar SVR12 rates in pts with or without baseline NS5A RAVs 12 pts with relapse, 10 in 8-wk arm 1 in 8-wk arm had emergent NS5A RAVs No NS5B RAVs at BL or time of failure No discontinuation of therapy due to AEs 10 pts with HIV-1 RNA > 50 at EOT 8 with repeat testing; 7 with suppression without change in ART; 1 with HIV-1 RNA of 59; 2 LTFU 2 with HIV VF = HIV-1 RNA 400 c/ml Wyles DL, et al. CROI Abstract 151LB. Reproduced with permission.

18 SVR12 Patients (%) Study HALLMARK-DUAL Daclatasvir + Asunaprevir: SVR Treatment naive Null/Partiall responders IFN ineligible/intolerant Breakthrough: 9 (4%) treatment naive, 26 (13%) nonresponders, 20 (9%) IFN ineligible/intolerant Relapse: 5 (3%) treatment naive, 7 (4%) nonresponders, 12 (6%) IFN ineligible/intolerant Serious AEs* occurred in 6% treatment-naive pts, 5% nonresponders and 7% IFN ineligibleintolerant pts AE leading to discontinuation in 3%, 1% and 1%, respectively Manns M., Pol S., Jacobson I. et al. Lancet, 2014

19 SVR12 (%) ION-4 Study: SVR12 Rates for Ledipasvir/Sofosbuvir in HIV/HCV Coinfection % 95% 97% 96% 94% Relapse (n=10) Overall (n=335) HCV Treatment Naïve (n=150) HCV Treatment Experienced (n=185) No Cirrhosis (n=268) Cirrhosis (n=67) No impact on SVR12 rate: gender, HCV genotype, baseline HCV RNA, IL28B genotype, cirrhosis, prior HCV treatment, ART regimens, and baseline CD4 count. Lower SVR12 rate observed among black patients (90%). Naggie S, et al. 22 nd CROI. Seattle, Abstract 152LB.

20 SVR12 (%) C-EDGE Co-infection: Key Findings n/n = 0 SVR12 With 12 Wks GZR/EBV According to Genotype / / / 44 27/ 28 All Pts GT1a GT1b GT4 Discontinued* Relapse Reinfection No subgroup provided efficacy advantage or disadvantage, including ART regimen New NS3, NS5A RAVs detected at failure in 4 of 5 pts who relapsed Short-lived HIV-1 RNA increases in 2 pts on ART during GZR/EBV treatment Both resuppressed HIV-1 RNA without change of ART During GZR/EBV Tx, no significant changes in CD4+ cell count GZR/EBV well tolerated: no pt discontinued for AEs and no serious treatment-related AEs *Unrelated to virologic failure. Rockstroh JK, et al. IAS Abstract TUAB0206LB. Rockstroh JK, et al. Lancet HIV. 2015;2:e319-e327. Reproduced with permission.

21 Pts With Potential Drug Interactions (%) How Frequent Are Significant Interactions Between HCV DAAs and ART? Retrospective analysis of pts with HIV/HCV coinfection (n = 125) 81% receiving TDF, 35% RAL, 16% EFV, 40% PI/RTV Drug interactions None Moderate Severe SMV + SOF LDV/SOF DCV + SOF OBV/PTV/R TV + DSV Langness J. HIV and Hep Clin Pharm Workshop Abstract 18.

22 HIV/HCV Drug Drug Interactions SMV + SOF LDV/SOF DCV + SOF OBV/PTV/RTV + DSV EBR/GZR Atazanavir + RTV Darunavir + RTV Lopinavir/RTV Tipranavir + RTV Efavirenz Rilpivirine Etravirine Dolutegravir or raltegravir Elvitegravir + COBI Abacavir/lamivudine * Maraviroc Tenofovir alafenamide Tenofovir DF/ emtricitabine nephrotoxicity No clinically significant interaction expected Potential interaction may require adjustment to dosage, timing of administration, or monitoring Do not coadminister Adapted from AASLD/IDSA. HCV guidelines. March 2016

23 AASLD/IDSA Guidance for HIV/HCV Co-infection Same recommendations as in HCV-monoinfected pts Main consideration is drug drug interactions between ART and HCV therapy Need to adjust or withhold RTV if receiving a boosted PI with OBV/PTV/RTV + DSV Potential for LDV-mediated increase in tenofovir levels, especially if tenofovir used with RTV-boosted PIs Avoid LDV with tenofovir if CrCl < 60 ml/min or if receiving tenofovir with RTV Other interactions at: aidsinfo.nih.gov/guidelines, hiv-druginteractions.org, hep-druginteractions.org AASLD/IDSA. HCV Management (February 24, 2016).

24 Changing ARV regime before the start of the treatment of Chronic Hepatitis C scheme with HCV PI Before the start of therapy of CHC patients already receiving effective ART (HIV RNA <50 copies/ml; CD4 + lymphocytes > 100 cells/mm 3 ): The treatment regimen of HIV infection (without reducing the effectiveness of ART) can be changed for the duration of the use of PI HCV (12 weeks of TVR and SMV, weeks for OMV/PTV/RTV, 44 weeks - for BOC). PI HIV (except ATV/r in combination with TVR and ATV combined with OMV / PTV / RTV) can at this time be replaced by RAL and, probably, DTG (coupled with BOC, TVR, SMV and OMV / PTV / RTV) or RPV (coupled with BOC, TVR or SMV), ETR (coupled with BOC or TVR). When used in ART mode drugs NVP or EFV changing the therapeutic regimen should be performed at least 1 week prior to initiation of therapy of CHC After the end of the treatment period, HCV PI can revert to the original regime of ART Protocols of follow-up and treatment of patients with HIV infection. Epidemiology and Infectious Diseases, 2015, 6, Supplement