HCV update Ardis Ann Moe

UCLA CARE clinic/NEVHC Van Nuys21 June 2014

amoe@mednet.ucla.edu

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.

Goals:

Terminology

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:◦ :http://www.mdcalc.com/child-pugh-score-for-

cirrhosis-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 NS5A 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

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

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.

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

Hep C meds to be approved

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 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.

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 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”.

Audience Response Question: Which is FALSE

5%

9%

50%

36% 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

Reinfection

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

Study of reinfection rates

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