VIRAL HEPATITIS: CHALLENGES IN MONITORING IVHEM 2016, AMSTERDAM, 3RD DECEMBER 2016

Transcription

1 VIRAL HEPATITIS: CHALLENGES IN MONITORING IVHEM 2016, AMSTERDAM, 3RD DECEMBER 2016 I. Andrieux-Meyer

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3 Declaration of interest No personal declaration of interest DNDi and Pharco are developping a HCV DAA combination based on sofosbuvir ravidasvir.

4 Responding to the needs of patients suffering from neglected diseases Sa'adia Khan-MSF Hepatitis C Sleeping sickness Mycetoma Chagas disease DNDi s PRIORITY: Neglected Patients Malaria Paediatric HIV Leishmaniasis Filarial diseases

5 HCV monitoring outline Discrepancies in Oraquick results No HCV RDT WHO validated Reliability of HCV genotyping Do we need to detect Y93H? APRI >2 as universal cutoff for cirrhosis? No SVR12 / 1 HCV viral load only? HCC monitoring? CAT/ DAA TT interruption Sofosbuvir and bradycardia

6 MSF multicentric prosceptive cohort study. Screening Results (I) with permission from Anne Loarec-Epicentre- 2014/2015- African HIV cohorts: low prevalence Sites Screened patients Positive HCV RDT Proportion of serology positive Positive VL / done VL Proportion of confirmed HCV Remarks Kenya Nairobi Mozambique Maputo Uganda Mbarara % 2/10 (20%) 0.04% % 26/30 (86%) 1.00% HIV cohort of Kibera complicated HIV patients or high risk groups % 5/17 (30%) 0.07% MoH HIV cohort Main reported risk factors : drug use Discrepancy with reported study results

7 MSF Screening Results (I) African HIV cohorts: Sites Kenya Nairobi Mozambique Maputo Uganda Mbarara Screened patients Positive HCV RDT Proportion of serology positive Positive VL / done VL Proportion of confirmed HCV (%) (%) (%) % 2/10 (20%) 0.04% % 26/30 (86%) 1.00% Remarks HIV cohort of Kibera complicated HIV patients or high risk groups % 5/17 (30%) 0.07% MoH HIV cohort

8 MSF Screening Results (II) In Asia and Middle East: Sites Cambodge Phnom Penh India Manipur Myanmar Yangon Myanmar Dawei Myanmar Kashin Myanmar Shan Uzbekistan Tashkent HIV cohorts Screened patients Positive HCV RDT Proportion of serology positive Positive VL / done VL Proportion of confirmed HCV % 60/149 (40.3%) 4.0% % 110/134 (82.1%) 6.8% % 507/577 (87.8%) 6.5% c % 314/358 (87.7%) 8.0% % NA NA % NA NA % NA NA

9 Access to reliable HCV screening: a game changer Globally, 59% of the world s population has no access to hepatitis C diagnostics. Diagnosis using serology is available in 53% of lower-middleincome countries, and 11% of low-income countries ( WHA report 2010). MSF recommends OraQuick (Orasure, USA): Best and most up to date performance but times more expensive than other RDTs.( 14 euros/test). Pooled procurement MSF: > 7$ (sensibility: 99.2%, specificity: 99.8% ( Lee 2010) Can be done on whole blood (e.g finger prick) or oral fluid. ( MSF HCV landscape analysis 2014) Limited evidence on the accuracy of HCV RDTs in HIV/HCV co-infection. ( Shivkumar Ann Intern Med 2012)( Smith J Itl Dis 2011). But 25 % false negative results in HIV co-infected people ( C.Kosack,2016), and need to recheck if CD4 < 50 and high suspicion of viral hepatitis.

10 Progress of the WHO-Prequalification, last update 10/2016 with permission A.Loarec PRODUCT NAME MANUFACTURER NAME DOSSIER REVIEW ON SITE INSPECTION LABORATOR Y EVALUATED ERP-D (4 th round) HCVSCAN EY Laboratories Ltd. Follow up amendment In process NA SD BIOLINE HCV Standard Diagnostics, Inc. Follow up amendment (under review) Stage complete Stage complete NA OraQuick HCV RDT OraSure Technologies, Bethlehem Abbreviated assessment Scheduled Scheduled NA Multisure HCV Antibody Assay MP Biomedicals Asia Pacific Pto, Ltd. Failed RightSign HCV rapid test cassette (Serum/Plasma) Hangzhou Biotest Biotech Co, Ltd. Notice of concern Xpert HCV Viral Load with GeneXpert Cepheid Abbreviated assessment Stage complete Information requested

11 Several hurdles Unknown quality of serological tests: No WHO prequalified tests HIV patients and other comorbidities Cross reactions Lack of quality control: Follow up of quality of the RDTs on the field QC process for VL QC for genotyping Access to PCR or VL: centralized, expensive Transport DBS storage What can and cannot be done on DBS Screening confirmation algorithm remains complex, expensive and not necessarily reliable.

12 WHO 2016 guidelines recommendations Core Ag 12 or 24 weeks = alternative if HCV RNA assays not available or affordable ---but Core AG POC is not available yet and not useful as proof of cure-- DBS =alternative to serum or plasma obtained by venipuncture for: antibody detection HCV RNA detection / quantification pre-treatment HCV Genotype or subtype determination BUT not for HCV core Ag, and not for proof of cure HCV VL : 1 pre treatment and and 1 at 12 weeks But what if people don t come back for SVR12??

13 Liver fibrosis assesment Adequate liver fibrosis assesment is crucial as long as treatment duration varies according to liver staging and eventually genotype. APRI is not validated in HIV-HCV or HIV-HBV co-infected individuals. Scaling up of Fibroscan liver assessment is hardly feasible in RLS. Fibroscan is not validated for children and pregnant women.

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15 Other monitoring questions RBV and longer TT duration Management of DAAs treatment interruptions Sofosbuvir and bradycardia DAA without any monitoring in non-cirrhotic patients?

16 How long will NS5a baseline RASs not matter?

17 Access to treatment for HBV is discriminatory

18 HBV monitoring outline No POC Hbe Ag testing available No POC HBV viral load testing available No POC HDV So the only test available is HBs Ag in ressource limited settings.

19 Integrated HIV-HBV-HCV PMTCT A public health approach for integrated HBV PMTCT in resource limited settings needs to take these diagnostic & monitoring limitations into account. Who should start TDF peripartum? When to start and when to stop TDF peripartum? What is the best monitoring post TDF PMTCT?

20 merci To all the patients and their families, the Pharco and DNDi staff. The MSF HCV working groupmsf teams : S.Delaunay, R. Malpani, C. Perrin, Y. Hu, J. Keenan, S. Shettle, T.Roth, G.Elder, L. Menghaney, S. Gupka, J.Burry, A. Loarec, M. de Souza, D. Maman, D. Donchuk, K. Herboczek,A. Mesic, C.Ferreyra,S. Balkan, M. Berthelot, J. Goiri, C. Jamet, M. Serafini, K.Lavelle, S.Cristofani, L.Molfino, M.Fernandez, P.Boulle, M.Serafini, MSF Ukraine, MSF India, MSF Myanmar, MSF Iran, MSF Pakistan, MSF Kenya, MSF Mozambique, MSF Chad/Mali, MSF Uganda. Contact: iandrieux-meyer@dndi.org