1. Sofosbuvir plus Peg-Interferon and Ribavirin in Treatment Experienced Patients with Hepatitis C Virus and HIV Co-Infection Mehri Nikbin, MD Infectious Diseases and Tropical Medicine specialist Iran Hepatitis Network (IHN) Middle East Liver Disease (MELD)

2. HIV / HCV co-infection is double trouble
Background
HIV / HCV co-infection is double trouble
Compared to HIV-negative individuals, those with HIV suffer:
Accelerated rate of fibrosis, higher rates of cirrhosis
Higher rates of decompensation & higher liver-related mortality
Unfortunately these patients have decrease access to liver transplantation compare with mono infected patients
To reduce the burden of HIV/HCV co-infection we must screen, test, and treat!

3. All HIV infected patients should be screened for HCV
Background
Treatment of HCV in this patients population should have a high priority
All HIV infected patients should be screened for HCV

4. Background
Treatment
HIV/HCV coinfected patients should be treated and retreated the same as patients without HIV
After recognizing and managing interactions with antiretroviral medications and direct acting antivirals (DAAs)
Antiretroviral drug switches ,when needed , should be done with goal of maintaining HIV suppression without compromising future options
(prior treatment history – response to antiretroviral therapy – resistance profiles – drug tolerance )

5. (FDA-approved as of February 12), 2016
Treatment of HCV/HIV co-infection, July 2016
Antiviral HCV Treatments
Daclatasvir + Sofosbuvir
(GT1,3)*
Monotherapies IFN-2a IFN-2b PEG-IFN 2a PEG-IFN 2b
IFN-2a + Ribavirin
IFN-2b + Ribavirin
PEG-IFN 2a + Ribavirin*
PEG-IFN 2b + Ribavirin
PEG-IFN + ribavirin plus either:
Boceprevir (GT1)
Telaprevir (GT1)
Simeprevir (GT1)
In combination with other agents:
Sofosbuvir
Elbasvir + Grazoprevir (FDC)
(GT1,4)*
Ledipasvir + Sofosbuvir (FDC)
(FDC, GT1,4,5,6*
Paritaprevir / ritonavir / ombitasvir (FDC) + dasabuvir (GT1)
Paritaprevir / ritonavir
/ ombitasvir (FDC) (GT4
Simeprevir + Sofosbuvir
(GT1)

6. Regimens not recommended for Patients with HIV/HCV
Treatment of HCV/HIV co-infection, July 2016
Regimens not recommended for Patients with HIV/HCV
Antiretroviral treatment interruption to allow HCV therapy is not recommended
Ribavirin should not be used with Didanosine/Stavudine or Zidovudine
Sofosbuvir-based regimen should not be used with Tipranavir
Should not be used treatment shorter than 12 weeks

7. Treatment Guidelines:
HCV/HIV treatment EASL guidelines :
Sofosbuvir ®+Dacatasvir®
Sofosbuvir®+Ledipasvir®
Sofosbuvir® +Peginterferon® +Ribaverin®
Less emphasis to Sofosbuvir ®+Ribavirin®
In genotype 1a,1b,4,5,6
Treatment duration is more systematically extended to 6 months in case of compensated cirrhosis

8. Sofosbuvir Interactions with Antiretroviral
Not metabolized nor induce or inhibit any cytochrome P450 enzyme
Drug interaction studies with antiretroviral drugs : no clinically significant interaction with Efavirez, Tenofovir, Emtricitabine, Rilpivirine, Ritonavir- boosted Darunavir, Raltegravir
Not recommended for use with Tipranavir

9. Study Design and Methodology
Treatment of HCV/HIV co-infection, July 2016
Study Design and Methodology

10. Study Design and Methodology
Treatment of HCV/HIV co-infection, July 2016
Study Design and Methodology
Prospective longitudinal study
Twenty patients with chronic HCV coinfected with HIV,undertreat ART and previously treated for HCV (Peginterferon® +Ribavirin®) and no SVR
All patients CD4 > 200
HCVRNA viral load :was assessed by Cobas Tagman assey with the low detection of 6 IU/ml
HCVRNA viral load : was assessed 4 weeks of therapy , and4 weeks and 12 weeks after end of therapy

11. Study Design and Methodology
Treatment of HCV/HIV co-infection, July 2016
Study Design and Methodology
All patients treated with ART continued which contained :
NNRT, NRTI,in some patients with PI
In two patients Zidovudine® changed
All patients treated for chronic HCV : Peginterferon a-2b® ( µg/week) plus oral Ribavirin® mg(based body weight) and Sofosbuvir® 400 mg/day for 12 weeks

12. Baseline Characteristics
Treatment of HCV/HIV co-infection, July 2016
Baseline Characteristics

13. Baseline Characteristics
Treatment of HCV/HIV co-infection, July 2016
Age (year)
45.15 (6.39)
Men
16 (80%) of 20 cases
Body-mass index (kg/m2)
25.02 (3.51)
Log10 HCV RNA (IU/mL)
5.92 (1.60)
HCV genotype 1a 1b
17 (85%)
3 (15%)
IL28b CC CT TT
6 (30%)
13 (65%)
1 (5%)
Fibroscan
F0-F1 F1
F1-F2 F2
F2-F3 F3
F3-F4 F4
4 (20%)
2 (10%)
Data are mean (SD) or n (%) unless otherwise stated

14. Treatment of HCV/HIV co-infection, July 2016
RESULTS

15. Treatment of HCV/HIV co-infection, July 2016
Results
SVR (cutoff HCV RNA :6 IU/ml) 3 months or 12 weeks after end of treatment: 19(95%)
RVR : all 19 patients had RVR
Non- Response :1(5%) (discontinued treatment due to liver decompensation)
Although Tenfovir® was included ART : no rising of BUN –Cr
The most common adverse effects : fever , fatigue , anemia (2 patients treated with Eprex® for anemia)

16. Sofosbuvir for chronic hepatitis C virus infection
Treatment of HCV/HIV co-infection, July 2016
Sofosbuvir for chronic hepatitis C virus infection
Rodriguez- Torres M,Gaggar A et al. J : acquire immune deific. syndrome , 2015 , 68:543-9
In this single-arm, single-site, open-label trial,
23 HCV/HIV coinfected treatment-naïve patients with genotype 1-4 received the 12- week
triple therapy of peginterferon alfa-2a, ribavirin (weight-based), and sofosbuvir.
Mean CD4 count was 562 cells/mm3 and all were on antiretroviral therapy (tenofovir-emtricitabine plusone of the following: efavirenz, atazanavir plus ritonavir, darunavir plus ritonavir, rilpivirine,or raltegravir).
The overall SVR12 was 91%; of the 19 patients with genotype 1, 89%
achieved an SVR12.

17. Treatment of HCV/HIV co-infection, July 2016
CONCLUSIONS

18. Treatment of HCV/HIV co-infection, July 2016
Conclusions
Peginterferon a2b(80-150µg/week) plus oral Ribavirin® mg(based body weight) and Sofosbuvir® 400 mg/day for 12 weeks provided high rate of sustained virology response in Iranian patients coinfected with HIV-1 and HCV genotype 1a-1b with compensated cirrhosis who had a history of nonresponse to Peginterferon a-2b.
These combination therapy is well tolerated in Iranian patient with coinfected HIV/HCV

19. Treatment of HCV/HIV co-infection, July 2016
Conclusions
At the time of this study ledipasvir +sofobuvir or Daclatasvir ® was not available in Iran.Daclatasvir in combination with Sofosbuvir is first choice for therapy in patients with HIV/HCV.
ILB 28 is not important for starting HCV treatment in HIV/HCV coinfected patients

20. Drug-Drug Interactions Remain Important for:
Treatment of HCV/HIV co-infection, July 2016
Drug-Drug Interactions Remain Important for:
CAT 1 = no DDI
CAT 2 = potential, may require
dose reduction or monitoring
CAT 3 = contraindicated
CAT 4 = unknown interaction
Martinello et al, CROI 2016, Abstract 451

21. Certain Safety Issues Regarding Regimens for HCV Genotype 1
Treatment of HCV/HIV co-infection, July 2016
Certain Safety Issues Regarding Regimens for HCV Genotype 1

22. Treatment of HCV/HIV co-infection, July 2016
Recommendation
HCV treatment in patients with HIV coinfection. AASLD/IDSA Guidance “The guidance from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of Am (IDSA)”.
ARV should be consider for most patients with HIV/HCV coinfection regardless of their CD4 count .
In naïve patients with CD4>500 ART could be deferred until after treatment of HCV.
For those patients whose CD4<200 it may be advisable to first initiate ART and defer HCV therapy