Ardis Ann Moe UCLA CARE clinic/NEVHC Van Nuys 21 June 2014

 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.

 Hep C viral load is not the same as HIV viral load ◦ 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: ◦ : cirrhosis-mortality/ 

 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

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

 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

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

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

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

 Daclatasvir: effective against genotypes 1,2,3 Ledipasvir: effective against genotype 1; to be combined with sofosbuvir into 1 pill a day

 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 CD4 <500 and get HIV viral load <50 copies for maximal response from hep C meds  If CD4 count >500, may be able to wait on starting HIV meds until after hep C treatment completed.

 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 hep c viral load at Week 8.  If 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”.

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 has 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

 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 July;59(1):45-51

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

 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 re- infected and will adhere to frequent clinic visits during treatment.