HCV update Ardis Ann Moe UCLA CARE clinicNEVHC

HCV update Ardis Ann Moe UCLA CARE clinic/NEVHC Van Nuys 21 June 2014 amoe@mednet. ucla. edu

Goals: � 1) terminology of hep C � 2) benefits of hep C treatment � 3)drug interaction issues with HIV meds �My thanks to my colleague Debika Bhattacharya for use of her slides for this presentation.

Terminology

� Hep load C viral load is not the same as HIV viral ◦ Hep C viral load does not correlate with risk of death, cirrhosis, liver damage.

� Hep C can be cured with current medications, unlike HIV. ◦ Cure=SVR “sustained virological response” ◦ Hep C viral load 6 months after completing treatment is undetectable = SVR

� CHILD score: A, B or C. (also scored numerically: 5 or more points) ◦ Risk of death from cirrhosis. ◦ Only to be used in patients with documented cirrhosis ◦ Important since simeprevir contraindicated in patients with CHILD score>5. (or B or C) ◦ Website for calculator for CHILD score: ◦ : http: //www. mdcalc. com/child-pugh-score-forcirrhosis-mortality/ �

Benefits of Hep C Treatment

� Patients who do develop cirrhosis have many problems: ◦ ◦ ◦ ◦ Esophageal varices and recurrent internal bleeding Ascites (fluid on the abdomen) Brain damage from hepatic encephalopathy liver cancer Problems with medications Leg edema Jaundice

� Even without cirrhosis, there are complications of hep C ◦ ◦ Fatigue Cryoglobulimia (kidney damage) Porphyria cutanea tarda Increased risk of diabetes

� Treatment of hep C reduces or eliminates risk of liver cancer, cirrhosis, cryoglobulinia, and porphyria. � However, cirrhosis is permanent scarring, so once there is cirrhosis, there is always some risk of liver cancer in the future, even if hep C cured. � Treatment of hepatitis C also appears to alleviate fatigue. Hepatology. 2014 Apr 5

Treatment issues with HIV

� HCV DAA (direct acting antiviral) Cheat Sheet ◦ PREVIR �Protease inhibitors: telaprevir, boceprevir, simeprevir ◦ BUVIR �Polymerase inhibitors �Sofosbuvir �ASvir �NS 5 A inhibitors: Daclatasvir, ledipasvir

IDSA Recommendations � IFN-free: � Genotype 1: Sim/Sof x 12 weeks (+/- ribavirin) � Genotype 2: Sof/ribavirin x 12 weeks � Genotype 3: Sof/ribavirin x 24 weeks � Genotype 4: Sof/rifabirin x 24 weeks

Side effects: � Simeprevir ◦ Rash including photosensitivity (28%), itching (22%), nausea (22%), shortness of breath (12%), elevated bilirubin (49%) �Note rash more likely in patients with cirrhosis

Side effects � Sofusbuvir ◦ ◦ ◦ ◦ ◦ Fatigue 59% headache 36% insomnia 25% chills 17% irritability 13% rash 18% itching 27% nausea 34% diarrhea 11%

Side effects of interferon

Side effects of simepravir/sofobuvir

� Overall <5% of study subjects stopped sofosbuvir and simeprevir on the COSMOS and other studies because of side effects.

Hep C meds to be approved � Daclatasvir: effective against genotypes 1, 2, 3 Ledipasvir: effective against genotype 1; to be combined with sofosbuvir into 1 pill a day

HIV/Hep C Drug interactions

� find those patients who need to be treated NOW with simeprevir/sofosbuvir, and who are willing to be on a limited HIV regimen (complera, isentress, truvada) in order to prevent drug interactions � Patients who are on Atripla, Stribild, or boosted protease inhibitors will have to wait until more hep C drugs available.

� Treat HIV first if CD 4 <500 and get HIV viral load <50 copies for maximal response from hep C meds � If CD 4 count >500, may be able to wait on starting HIV meds until after hep C treatment completed.

Treatment Schema

� Obtain baseline hep C viral load (within 3 months of beginning treatment) � Counsel patient on need to take all meds � Counsel patient on need to avoid sunlight, risks of nausea and rash � Alter patient’s HIV regimen if necessary.

� Follow-up 2 weeks and at 4 week point after initiating hep C meds to check on adherence and immediate side effects. Mild rash can be treated through with benedryl, topical steroids � Check CBC, platelets, AST, ALT every 2 weeks during first 4 weeks. � Repeat Hep C viral load at Week 4 point

� Hep C viral load should be <25 copies at Week 4 point; if not, patient may need to be discontinued to prevent resistance. � Recheck � If hep c viral load at Week 8. hep c meds tolerated, see patient at Week 4, Week 8 and Week 12 and check CBC, platelets, AST, and ALT at each visit(or monthly if being treated x 24 weeks)

� If patient on ribavirin containing regimen, dose reduce ribavirin if anemia develops: Hb < 10 � Most anemia with Sof/ribavirin mild.

� Repeat Hep C viral load 6 months after completing therapy to ascertain cure: “SVR”.

Audience Response Question: Which is FALSE 1)hep C viral load of 2, 000 copies may be a patient undergoing self-cure 2)a patient who is cured of hep C but still ha cirrhosis has no risk of liver cancer 3)simeprevir has multiple drug interactions with many HIV medications 4)patients cured of hep C have less fatigue

Reinfection

Study of reinfection rates � 191 MSM with cured (treated with meds) or spontaneously cleared hep C ◦ ◦ ◦ 44 were reinfected 8 were infected several more times Same or different genotypes None had IDU risk factor Estimated that 25% will be re-infected within 2 years of cure. ◦ AIDS 2013 Oct 23; 27(16): 2551 -7

� Prison populations in Spain: ◦ 119 Hep C Ab+, cured or spontaneously cleared while as inmate. 81% hx of IDU ◦ Reinfection rate 5. 37 per 100 person years, higher in active IDU and HIV co-infected ◦ J Hepatology. 2013 July; 59(1): 45 -51

� Selection of patients for hep C treatment will have to include safe sex counseling and sobriety

Conclusions

� Interferon free hep C drugs are here, and more coming � Be prepared for elaborate PA process to get the meds � Treatment will reduce complications of hep C infection and improve quality of life � Select patients who are not likely to get reinfected and will adhere to frequent clinic visits during treatment.