HCV Diagnostics Technology Landscape AIDS 2014, 10 th International AIDS Conference 21 July 2014 Maurine M. Murtagh UNITAID Consultant

Current HCV Testing Continuum ILLUSTRATIVE With available HCV treatment, the testing cascade for HCV is complex and expensive, which means that it is very challenging for resource-limited settings. With the potential availability of DAAs, a simplified HCV testing algorithm should be possible, which will help make HCV diagnosis and monitoring attainable in resource- limited settings. Serodiagnosis RDT HCV RNA or Ag Line Probe RT PCR Biopsy Bio- Marker HCV RNA Need for Service Screening Confirmatory Test Treatment Monitoring Genotyping Fibrosis Staging Prognostic Markers IL- 28B

Potential HCV Testing Continuum - DAAs ILLUSTRATIVE Screening and confirmatory testing will still be needed, although these might be combined into a single qualitative assay to detect the presence of HCV RNA or Ag. Fibrosis staging may be needed, although perhaps not for HIV co-infected patients, and testing HCV clearance/cure at the end of treatment and post-treatment, will also be required. But, qualitative HCV RNA or Ag technologies used for confirmation/diagnosis of HCV could also be used for clearance/cure testing. Serodiagnosis RDT HCV RNA or Ag Need for Service Screening Confirmatory Test Test of Cure Fibrosis Staging Fibrosis Staging Bio- marker TE Bio- marker TE HCV RNA or Ag

Pipeline Technologies – Confirmation/Cure With all-oral HCV regimens expected in ~2016, it is anticipated that baseline quantification of HCV may not be necessary. It is also anticipated that with shorter and more effective regimens, quantitative HCV RNA testing for treatment monitoring can be eliminated. It would then be possible to use a highly sensitive qualitative HCV RNA assay or HCV Ag assay to confirm the presence of the virus (for diagnosis) and to use the same assay again at the end of treatment and at a defined point post-treatment to confirm cure.

Existing Technologies – Confirmation/Efficacy/Cure Assays include those from Roche (COBAS®), Abbott (m2000), Siemens (VERSANT®), and others. These pose access challenges similar to those for HIV viral load testing. Solutions include the use of DBS for HCV viral load testing as well as the introduction of platforms that can be used nearer to the point of patient care. Currently, both qualitative HCV testing for confirmation of HCV diagnosis and quantitative HCV viral load testing for monitoring treatment efficacy and clearance and is done on sophisticated platforms requiring highly trained personnel in central laboratory settings.

Some Potential HCV RNA and HCV Ag Products Low-Resourced Lab (minimal to no sample prep) Point-of-Care Wave 80 EOSCAPE™ IQuum Liat™ Analyzer Cepheid GeneXpert® Quantitative Molbio Truenat HCT Alere qDaktari HCV Quantitative Viral Load Assay TypePCR NATbDNA- based NAT Portable, ~8lbs PCR NATRT PCRPCR NAT Portable, <11lbs HCV Core Antigen, Portable, 5.5lbs Pan- genotypic YesUnknownYes Unknown Time to Result 70 min30-35 min~95 min~ min30 min Battery Life8 hoursUnknownAC Power8 hours Up to 3 days Device Cost<$10,000~$25,000$17,000$8,000TBD$5,000 Cost/ Test<$20TBD$10 - $17$15TBD$8 Market Launch for HCV Not known Ex-US launch early 2015 Not known Late 2015 (Medium) (Low) COMPLEXITY

Conclusions/Questions More and better RDTs for screening HCV are needed, including RDTs that can reliably detect HCV in HIV co-infected patients. More studies are needed to demonstrate that HCV Ag assays that detect HCV core antigen are sufficiently sensitive for use in diagnosis and testing for HCV clearance/cure. While there is a reasonable pipeline of HCV viral load assays for use on platforms at the point of care in resource-limited settings, most developers are aiming for fully-quantitative assays. Is this what is really required in light of the advent of all-oral HCV treatment regimens?

Conclusions/Questions In general, developers need guidance from stakeholders with respect to the key market requirements for HCV screening/diagnosis as well as monitoring, if any, and/or clearance/cure testing for HCV. Stakeholder- vetted TPPs could be helpful in this respect. If the cost of DAAs can be brought down to levels where all-oral treatments for HCV are obtainable in resource-limited settings, the required diagnostic technologies need to be ready and appropriate for implementation. Like HIV, this testing landscape is likely to include both lab-based platforms and diagnostics for use at or near the point of patient care.

Acknowledgements Thanks to UNITAID for funding my diagnostic landscape work.

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