How to treat HCV in HIV coinfection

Transcription

1 How to treat HCV in HIV coinfection Dr. med. Stefan Mauss Center for HIV and Hepatogastroenterology Duesseldorf, Germany

2 These are real world cases from a rather wealthy social health care system off label use included

3 Case 1 male, 35 years, 18 cm, 81kg Factor VII deficiency (intermittent substitution with 2-3 IU required) HIV+ partner, HIV- child 2 years old chronic hepatitis C (genotype 1a) - ALT 112 U/L, AST 99 U/L, GGT 48 U/L - Fibroscan 21.3 kpa (=METAVIR F4) - hcv-rna 96, IU/ml - ultrasound: small, dense liver, no focal lesions, spleen enlarged (22,2 cm in diameter) Leukocytes 13/µl, platelets 54./µl Partial response to PegIFN + RBV (12 mg/d) in 21

4 Case 1

5 Case 1 HIV CDC B3 - diagnosis 1984, - ART since 1991, - CD4+ 13/µl (21%) - HIV-RNA <2 copies/ml HIV therapy never failed Current antiretroviral therapy TDF + 3TC + SQV/r + Cotrim

6 Case 1 Re-Treat hcv? Adjust antiretroviral therapy first? Which hcv therapy? Anything else to consider?

7 Case 1 Neutropenia G-CSF 15 Mio IU/bd Thrombopenia Ribavirin priming Eltrombopaq? dosing?

8 Case 1 HIV-RNA cp/ml HCV RNA IU/mL CD4+ cells/µl Leukocytes/nL haemoglobin g/dl platelets/nl TDF+3TC+INV/r RBV TDF+3TC+ATV/r 3 PegIFN Telaprevir 25 HIV RNA, HCV RNA G-CSF 2 15 CD4+cells, platelets 1 5 haemoglobin leukocytes

9 Eltrombopag for thrombopenic patients with liver cirrhosis Median Platelet Counts (ITT) 94% of patients from Part 1 entered Part 2 Median Platelet Count (x 1 3 /µl) Part 1 Part 2 Threshold for dose reduction Placebo Eltrombopag Follow-Up OLB 2 AVB Time Since Randomization (Weeks) Placebo Eltrombopag AWB, antiviral baseline, OLB. Open-label baseline Dusheiko EASL 212 #6

10 Eltrombopag in patients with liver cirrhosis and thrombopenia Virologic Response (ITT) Patients (%) 2.7% 95% CI: P<.1 9.1% 95% CI: P= % 95% CI: P<.1 Thromboembolism and portal vein thrombosis (n=27 (5%) 6.% vs. n=1 (,5%) 95% CI: P=.22 Virologic Response Dusheiko EASL 212 #6

11 Case 1 HIV-RNA cp/ml HCV RNA IU/mL CD4+ cells/µl Leukocytes/nL haemoglobin g/dl platelets/nl TDF+3TC+INV/r RBV TDF+3TC+ATV/r 3 HIV RNA, HCV RNA 1 PegIFN Telaprevir G-CSF Etrombopag 5 mg/d CD4+cells, platelets haemoglobin leukocytes

12 Case 1 Patient presented with multiple enlarged cervical lymph nodes Plasmoblastic lymphoma (diffuse large B-cell lymphoma, EBV associated)

13 Case 1 HCV therapy was stopped at week 38 Patient had 3 courses of CHOP + 2 Gray radiation In PET CT no signs of vital tumor HCV? Was this a coincidence or was the cocktail of immune modulators/growth factors too much?

14 Case 2 Male 4 years old Didn`t see a doctor since HIV diagnosis in 26 Active syphilis at first presentation Unsafe sex MSM with presumed HCV-positive partner about five weeks ago CD4 512/µl (1%), HIV RNA 26,282 copies/ml ALT 165 U/l, AST 61 U/L, HCV-RNA 36,2, IU/ml, IL28B CC

15 Case 2 Is this acute hepatitis C? Impact of syphilis? What about HIV therapy? Which hiv therapy to start with? Which hcv therapy to start with?

16 Case 2 HIV-RNA cp/ml HCV-RNA IU/mL CD4+ cells/µl Leukocytes/nL haemoglobin g/dl platelets/nl HIV RNA, HCV RNA 1 TDF+FTC+ATV/r PegIFN CD4+cells, platelets

17 Case 2 Stop hcv therapy? Intensify hcv therapy?

18 Case 2 HIV-RNA cp/ml HCV-RNA IU/mL CD4+ cells/µl Leukocytes/nL haemoglobin g/dl platelets/nl TDF+FTC+ATV/r 9 HIV RNA, HCV RNA PegIFN RBV Telaprevir CD4+cells, platelets

19 Case 2 HIV RNA, HCV RNA haemoglobin. leukocytes HIV-RNA cp/ml HCV-RNA IU/mL CD4+ cells/µl Leukocytes/nL haemoglobin g/dl platelets/nl TDF+FTC+ATV/r PegIFN RBV Telaprevir CD4+cells, platelets

20 Case 2 Treatment duration?

21 Case 3 57 years, male, former ivdu 185 cm, 85 kg HIV CDC B2 CD4 416/µl (22%), HIV-RNA <2 copies/ml Kivexa 1x1, Raltegravir 4 mg 2x1 HCV GT2b ALT 31 U/l, AST 32 U/l Fibroscan 13 kpa Relapse after PegIFN/RBV for 2 weeks in 21 IL28B CC Arterial hypertension Ramipril 1 mg/d Metoprolol 95 mg/d Nitrendipine ret 2 mg/d Increase in creatinine and proteinuria on tenofovir (28)

22 Telaprevir activity on different hcv genotypes Monotherapy 3x75mg Telaprevir for 2 weeks HCV RNA log1 Abfall ,4 3,9,5,9 GT 1 GT2 GT3 GT4 Viral decay after 2 weeks Reesink et al., Gastro 26, Foster et al., EASL 29, Benhamou et al., EASL 29, #1

23 Case 3 HIV-RNA cp/ml HCV RNA IU/mL CD4+ cells/µl platelets/nl creatinine mg/dl HIV RNA, HCV RNA 1 3TC+ABC+RAL PegIFN+RBV Telaprevir CD4+cells, platelets creatinine

24 Case 3 HIV-RNA cp/ml HCV RNA IU/mL CD4+ cells/µl platelets/nl creatinine mg/dl HIV RNA, HCV RNA 1 3TC+ABC+RAL PegIFN+RBV Telaprevir CD4+cells, platelets creatinine

25 Case 3 Why did renal decompensation happen? - Drug drug interactions? - Renal toxicity of hcv therapy? - Comorbidities?