1. به نام خداوند بخشنده مهربان

2. Treatment of HIV/HCV & HIV/HBV coinfection Dr. Davoudi Infectious diseases specialist Antimicrobial research center Mazandaran University of Medical Sciences

3. HIV/HCV coinfection As the introduction of ART reduced dramatically the frequency of life-threatening opportunistic infections and malignant diseases and improved survival, hepatitis C emerged as an important cause of morbidity and mortality in persons with HIV Because of the common, bloodborne routes of acquisition of HIV & HCV, approximately 1/3of patients with HIV infection (3/4 in the subset with injection-drug use) are coinfected with HCV

4. HIV-HCV CO INFECTION Indications for HCV treatment in HCV/HIV coinfected persons are identical to those in patients with HCV monoinfection

5. Indications for treatment

6. Approved HCV drugs

7. TREATMENT OF HIV-HCV CO INFECTION If CD4+ T-cell counts are normal, patients with HIV HCV coinfection could respond to antiviral therapy with standard or PEG IFN plus RBV, but the likelihood of an SVR was approximately half to two thirds

8. HIV-HCV CO INFECTION The same IFN-free treatment regimens can be used in HIV-coinfected patients as in patients without HIV

9. Genotype 1, IFN-free Option 1 Sofosbuvir (400 mg) and ledipasvir (90 mg) in a single tablet administered once daily 12 weeks Treatment may be shortened to 8 weeks in treatment naïve patients without cirrhosis if their baseline HCV RNA level is below 6 million (6.8 Log) IU/ml. This should be done with caution, especially in patients with F3 fibrosis,

10. Genotype 1, IFN-free Option 1 Patients with compensated cirrhosis sofosbuvir(400 mg) and ledipasvir (90 mg) in a single tablet administered once daily+daily ribavirin for12 weeks Without ribavirin for24 weeks

11. Genotype 1, IFN-free Option 4 Daily sofosbuvir (400 mg) and daily daclatasvir (60 mg) for 12 weeks Adding daily ribaverin is recommended in patients with cirrhosis In patients with cirrhosis with contra indications to the use of ribavirin, extending duration of treatment to 24 weeks must be considered

12. Genotype 2, Option 1 Ribavirin and sofosbuvir for 12 weeks Therapy should be prolonged to 16 or 20 weeks in patients with cirrhosis

13. Genotype 2, Option 3 Cirrhotic and/or treatment-experienced patients can be treated with an IFN-free combination of daily sofosbuvir and daily daclatasvir for 12 weeks

14. Genotype 2, Option 2 Cirrhotic and/or treatment-experienced patients can be treated with weekly PegIFN-α, daily ribavirin and daily sofosbuvir (400 mg) 12 weeks

15. Genotype 3, Option 1 Ribavirin and daily sofosbuvir for 24 weeks In patients who failed to achieve an SVR after sofosbuvir plus ribavirin treatment weekly PegIFN-α, daily and daily sofosbuvir (400 mg) 12 weeks

16. HCV treatment

17. Sofosbuvir 80% of Sofosbuvir is renally excreted, whereas 15% is excreted in faeces No dose adjustment of sofosbuvir and ledipasvir is required for patients with mild or moderate renal impairment No sofosbuvir dose recommendation can be given for patients with severe renal impairment

18. Sofosbuvir Transporting by P-glycoprotein (potent inducers decrease sofosbuvir plasma concentrations) should not be administered with other known inducers of P-gp,such as: rifampin, carbamazepine, phenytoin

19. Drug-drug interactions between HCV DAAs and HIV antiretrovirals Known or anticipated increase in tenofovir concentrations with boosted regimens and with efavirenz and rilpivirine when given sofosbuvir plus ledipasvir caution and frequent renal monitoring needed.

20. Drug-drug interactions between HCV DAAs and HIV antiretrovirals Green: No clinically significant interaction expected Amber:Potential interaction which may require a dosage adjustment, altered timing ofadministration Red: should not be co administered

21. Drug-drug interactions between HCV DAAs and HIV antiretrovirals Ledipasvir/sofosbuvir may be given with all antiretrovirals due to an increase in tenofovir concentrations when a pharmacokinetic enhancer (ritonavir or cobicistat) is present inan antiretroviral regimen, these combinations (i.e atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, elvitegravir/ cobicistat, darunavir/cobicistat, all in combination with tenofovir/ emtricitabine) should be used with cautionwith frequent renal monitoring if other alternatives are not available

22. Drug-drug interactions between HCV DAAs and HIV antiretrovirals The daily daclatasvir dose should be adjusted to 30mg daily in HIV-infected patients receiving atazanavir/ritonavir and to 90 mg daily in those receiving efavirenz

23. Drug-drug interactions between HCV DAAs and HIV antiretrovirals No drug-drug interaction has been reported between sofosbuvir and antiretroviral drugs

24. Drug-drug interactions between HCV DAAs and HIV antiretrovirals The fixed-dose combination of sofosbuvir and ledipasvircan be used with all antiretrovirals. this regimen should not be used with the combination of tenofovir/emtricitabine with atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir or elvitegravir/cobicistat when possible, or used with caution with frequent renal monitoring

25. TREATMENT OF HBV / HIV INFECTION

26. Approved Antiviral Therapies of HBV infection

27. TREATMENT OF HBV / HIV INFECTION Regardless of CD4 cell count or need for HBV treatment ART that includes agents with activity against both HIV and HBV is recommended for all patients coinfected with HIV and HBV For HIV/HBV coinfected individuals, ART MUST include two drugs active against HBV, preferably tenofovir and emtricitabine, regardless of the level of HBV DNA Fixed-dose coformulation of tenofovir/emtricitabine or abacavir/lamivudine

28. HBV HIV INFECTION If Tenofovir can not be safely used,Entacavir should be used In patients who have already recieved lamimudine or have known lamivudine resistance: A higer dose of Entacavir(1 mg) HBV DNA should be monitor frequently

29. HBV HIV INFECTION If HBV needs treatment & ART regimen cannot be used, Drugs active only against HBV (donot lead to HIV drug resistance);such as Adefuvir, PEG IFN, Telbivudine is not recomended: Intermediate rate of vresistance in mono infection and unknown rates in coinfection

30. References 1.Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Aidsinfo 2016 2.EASL Recommendations on Treatment of Hepatitis C 2015 3.Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 2015

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