Cases: Treatment of Hepatitis C in HIV/HCV Coinfection

Transcription

1 Cases: Treatment of Hepatitis C in HIV/HCV Coinfection David L. Wyles, MD Professor of Medicine University of Colorado Chief, Division of Infectious Disease Denver Health Learning Objectives After attending this presentation, learners will be able to: List the key antiretroviral classes which are likely to have significant drug interactions with DAA regimens Determine key baseline screening labs necessary in HIV + persons prior to initiating DAA therapy Recognize at risk population for HCV re-infection after DAA treatment Slide 2 of 29 Case 1 38 transgender female referred from PCP for HCV evaluation Labs available on referral +HCV AB GT 1a, 385,000 IU/mL ALB 4.0 AST 21 ALT 66 TB 0.5 Cr 0.78 GC/Chlamydia negative Meds: estradiol 4mg, Spironolactone 100mg History of IDU since age 15- says has no injected for about 4 months Initially identified as gay. Sex with both men and women. Not aware of prior STIs. Currently in relationship with a woman. Exam is unremarkable except moderate gynecomastia Slide 3 of 29

2 ARS Question 1: What additional screening tests are indicated? 1. HIV test 2. Hepatitis A IgM 3. Hepatitis A total Ab 4. Hepatitis B serologies (core total, sag, sab) 5. 1, 3, and 4 Slide 4 of 29 Low rates of screening, high rates of HIV and HCV in transgender patients NYC- 203 pts at least 2 visit and on hormonal therapy Prevalence HBV 0.89% HCV 1.78% HIV 2.22% Italy- 243 transgender patients HCV prevalence 4-8% HIV in 12.1% of MtoF patients Slide 5 of 29 Don t forget about HAV screening and vaccination EU: 4,096 suspected acute HAV cases (JUN 16-MAY 17) NYC 2017: 51 confirmed cases in MSM Typically <3 cases/year in NYC in MSM Slide 6 of 29

3 Case continued Rapid HIV + VL 3,633 CD4 470 (26%) HAV immune, HBV unexposed/non-immune Slide 7 of 29 ARS Question 2: How would you proceed? 1. Treat HIV first, using boosted integrase inhibitor regimen 2. Treat HIV first, using boosted-pi regimen 3. Treat HCV first to avoid immune-reconstitution HCV flare 4. Treat HCV first to decrease the risk of ART induced hepatotoxicity 5. Treat HIV first using unboosted integrase inhibitor regimen 6. Something else Slide 8 of 29 Initiate ART As Soon As Possible After HIV Diagnosis Rapid start (including same day as diagnosis) ART, unless that patient is not ready to commit to starting therapy o Structural barriers should be removed Samples for HIV-1 RNA level; CD4 cell count; HIV genotype for NRTI, NNRTI, and PI; HLA-B*5701 testing; laboratory tests to exclude active viral hepatitis; and chemistries should be drawn before beginning ART, but treatment may be started before results are available. NNRTIs (possible transmitted resistance) and abacavir (without HLA-B*5701 results) should not be used for rapid ART start ART should be started as soon as possible (but within 2 weeks) after diagnosis of most opportunistic diseases Slide 9 of 29 Saag, Benson, Gandhi, et al, JAMA, 2018.

4 HIV treatment does not completely abrogate the negative effect on HCV Slide 10 of 29 ART decreases hepatic decompensation events: 0.72 ( ). Recommended Initial Regimens: InSTI Plus 2 nrtis Bictegravir/TAF/emtricitabine Dolutegravir/abacavir/lamivudine Dolutegravir plus TAF/emtricitabine Slide 11 of 29 Saag, Benson, Gandhi, et al, JAMA, Case continued She starts on DTG+TAF/FTC. In one month: HIV RNA<30. No side effects. FIB-4=0.53 Enhanced fibrosis test estimated stage F1. She is eager to start HCV therapy. GT1a treatment naïve, VL initially 385,000 but repeat 4 months later: 3.4 million Meds: ARVs plus estradiol 4mg, spironolactone 100mg Slide 12 of 29

5 ARS Question 3: Insurance approved GLE/PIB 8 weeks. Is this an appropriate treatment duration/regimen in this setting? 1. NO, it was not studies at 8 weeks in co-infection 2. NO, it was studied and SVR was inferior to 12 weeks 3. YES, it was studied and resulted in high SVR (98%) 4. YES, it was not studied but Aronsohn says it is ok 5. NO, because of a drug interaction with her estradiol 6. NO, because of a drug interaction with her ARVs Slide 13 of 29 GLE/PIB in HIV/HCV Coinfection: EXPEDITION 2 8 Weeks G/P N=137 (No Cirrhosis) 12 Weeks G/P N=16 (Cirrhosis) SVR12 SVR12 Day 0 Week 8 Week 12 Week 20 Week 24 Posttreatment Week 24 GT3 TE excluded Most ART allowed: boosted regimens (DRV, LPV, or EVG) Only 1 on EVG/cobi; no boosted PIs enrolled Demographics: 8-wk treatment course 18% Black 19% TE 16% GT3 88% F0-F1 Patients With SVR12, % BT SVR12 ITT mitt Noninferiority Threshold BT= GT3 wk 8 93% SVR in cirrhotics (14/15) Slide 14 of 29 HCV DAAs and ARVs: INSTIs and tenofovir Slide 15 of 29

6 Issues with estrogens and G/P, but Slide 16 of 29 Estradiol Ethinyl Estradiol Different pharmacology- EE higher oral bioavailability and increased hepatic concentrations 18 women in phase 2/3 G/P studies on Estradiol No increased incidence of LFT elevations noted ClinPharmR.pdf Phone consult with Dr. Kiser. Probably ok to use but would monitor LFTs. Patient is started on G/P and HCV RNA 0 at week 4. Slide 17 of 29 Case 2: Doc, I don t want to change my HIV pills 57 Hispanic man GT3a with compensated cirrhosis, DM, HTN, HLD. HCV treatment naïve. GT3a 976,000 IU/mL NS5A: no Y93H Labs: ALB 3.5 TB 0.8 AST 53 ALT 47 PLT 103 US: nodular appearing liver, spleen 14.5cm, PV 14mm Other meds: amlodipine 10mg, atorvastatin 10mg, metformin 500mg BID ART: TDF/FTC + DRV/rit 800/100mg QD Prior EFV/TDF/FTC failure- M184V, K103N Does not want to switch ART Slide 18 of 29

7 ARS Question 4: What is the best treatment option if you keep him on his current ARVs? 1. G/P for 12 weeks 2. G/P for 16 weeks 3. SOF/VEL for 12 weeks 4. SOF/VEL/VOX for 12 weeks 5. There are no good options- he needs to change ARV first Slide 19 of 29 Drug interactions with antiretrovirals Slide 20 of 29 Doarvirine (NNRTI): no anticipated to have significant interactions with DAAs Very limited data on VOX with HIV Pis (no treatment data) DRV/rit not studied clinically with SOF/VEL/VOX Impact of DRV/rit (800/100mg) on VOX GMR Cmax AUC Cmin Cirrhosis also impact VOX concentrations CTP A: 73% increase in AUC CTP B/C: 299%/500% increase Slide 21 of 29

8 SOF/VEL in HIV/HCV Coinfection: ASTRAL-5 Patients With SVR12 by Genotype, n/n (%) Week N= SOF/VEL Eligible ARV regimens RPV RAL or EVG/c PI/r (47%) TDF (86%) 53% boosted TDF regimen SVR12 Demographics 86% male 45% Black 18% cirrhosis 62% GT1a 11% GT3 Patients With SVR12, % Relapse 1 LTFU 1 LTFU Total 1a 2b Genotype Patients with SVR12 in key subgroups: Patients with cirrhosis: 19/19 (100%) Treatment-experienced patients: 29/31 (94%) Withdrew Consent Slide 22 of 29 SOF/VEL: no significant change in CrCl on study 140 Non-boosted TDF Boosted TDF Non-TDF containing regimen N=35 N=56 N=15 Median Creatinine Clearance (ml/min) Weeks 60 BL FU-4 FU Median CL cr, ml/min discontinuations due to AEs Day 4 due to N/V (by pt) Day 48 due LFT elevations Judged not drug related by investigator Intercurrent infection and antiboitic use Pt achieved SVR12 Slide 23 of 29 FU-4/12, follow-up Week 4/12; Creatinine Clearance calculated using the Cockroft-Gault method; errors bars represent Q1, Q3. ARS Question 5: The patient is treated with 12 weeks SOF/VEL and is cured. He asks if he can be re-infected. He is MSM with h/o GC, syphilis and multiple partners. Which of these risk groups do data suggest is at highest risk for reinfection with HCV? 1. PWID with ongoing injection drug use 2. HIV+ MSM with multiple high risk sexual behaviors 3. Prisoners 4. Heterosexual couple where the partner remains HCV RNA+ Slide 24 of 29

9 HCV re-infection rates from published studies 5-year re-infection rate (%) patients 4.1 years 0.9% 1203 patients 5.0 years 8.1% 1285 patients 3.3 years 21.8% Low risk IVDU/prisoner HIV co-infected Slide 25 of 29 HCV RE-INFECTION: The Achilles Heel for HCV elimination in HIV/HCV Slide 26 of 29 Ingiliz P. J Hepatol Ingiliz P. #612 CROI Persons With Reinfection, % /100 P-Y GECCO Cohort: 2239 P-Y follow-up 12% MSM, 37% IDU 87% of reinfections: MSM 83% of reinfection: HIV P-Y follow-up 0.7/ P-Y /100 P-Y Overall IDU MSM Transmission mode HCV RE-INFECTION: The Achilles Heel for HCV elimination in HIV/HCV Slide 27 of 29 NEAT Network 7.3/100 py 27/64 second re-infection (18.8/100 py) Ingiliz P. J Hepatol Ingiliz P. #612 CROI Persons With Reinfection, % /100 P-Y GECCO Cohort: 2239 P-Y follow-up 12% MSM, 37% IDU 87% of reinfections: MSM 83% of reinfection: HIV P-Y follow-up /100 P-Y /100 P-Y Overall IDU MSM Transmission mode

10 Take home points HIV accelerates the natural history of HCV Treatment of HIV does not completely reverse the adverse impact HCV treatment indicated for all HIV co-infected Plentiful treatment options exist and work just as well in HIV Drug interactions are generally manageable Effective HCV treatment can avert complications More data are needed with long-term follow-up after DAA therapy Re-infection is an issue Enhanced/better prevention efforts are needed Slide 28 of 29 Question-and-Answer Remember to raise your hand and wait until you have the microphone before you ask your question we are recording! Slide 29 of 29