1. The Current Pipeline for Point-of-Care Virologic Testing for HIV/AIDS Scaling up Virologic Diagnostic HIV Testing in Infants and Rationalizing Decentralization of Testing Through the Use of Point-of-Care Technologies 22 July 2014 Maurine M. Murtagh UNITAID Consultant

2. The Tiered Laboratory System in Resource-Limited Settings With the exception of lateral flow rapid testing for detection of HIV, most testing (e.g., viral load and EID) is done at levels 3 and 4 of the system, while most patients present at Level 1 or Level 0, where testing capabilities are limited or non-existent. 4 - National Reference Laboratory Senior health specialists 3 - Regional/provincial Laboratories Specialists/senior technicians 2 - District Hospital Technicians and assistants 1 - Primary care Health Centers Health Posts and Outreach 0 - Primary care Health Posts and Outreach

3. This mismatch has led to a rush towards decentralized testing

4. But, is that enough? Arguably, no. Some tests we think of as being inherently POC tests (e.g., RDTs) and some we think of as being inherently non-POC tests (e.g., Roche COBAS® TaqMan®), but in theory either could provide POC testing. Neither location nor technology necessarily defines POC testing, rather there are critical features of the testing process that will define whether it is POC testing: Ability to perform the test and provide a test result to the patient or caregiver on the same day he/she presents At a site where linkage to appropriate clinical decision making is available at the same patient visit. Same day testing and clinical care are especially vital in EID given the extensive loss to follow-up that has been experienced in many settings using DBS to transport samples to central laboratories for testing. Even with improved results return using SMS or other mobile technologies, loss to follow-up of infants is significant.

5. For example, the SAMBA I platform from Diagnostics for the Real World will offer both a viral load and an EID assay. The semi-quantitative viral load assay is already available in Kenya, Malawi and Uganda. Alere q is being launched initially for HIV detection, including EID, but will ultimately have a quantitative viral load assay. NWGHF LYNX HIV p24 Antigen Test is the only platform currently in the pipeline dedicated entirely to EID. New Options for Viral Load Monitoring are on the Horizon A number of new viral load and/or EID diagnostic platforms for use at or near the point of patient care are either in the market or in development. These will have lower instrument and per-test costs, but will also have lower throughput than lab-based systems.

6. 2015 2013 2014 2016 Alere q Alere SAMBA I VL DDU/Cambridge Liat™ Analyser Iquum/Roche EOSCAPE HIV™ Wave 80 Biosciences GeneXpert Cepheid Savanna Viral Load Platform NWGHF Viral Load Assay with BART Lumora *Estimated as of May 2014 - timeline and sequence may change. No market launch date set by company. Truelab PCR Molbio/bigTec RT CPA HIV-1 Viral Load Ustar Gene-RADAR Nanobiosm LYNX HIV p24 Antigen NWGHF POC Viral load & EID products: available and pipeline* Micronics SAMBA EID DDU/Cambridge ZIVA™ Cavidi

7. Summary of POC Viral Load/EID Platform Characteristics Characteristic Use SettingMix of Level 1 and Level 2 settings, often driven by need for plasma specimen for quantitative viral load. TypeVariety of molecular platforms – PCR, iNAAT, etc. Most platforms are benchtop; many are portable. QuantitationAll quantitative assays, with the exception of SAMBA 1 and 2, are fully quantitative; one assay (LYNX) is dedicated to EID only, and at least 4 of the viral load platforms will have DNA assays for EID. Lower LODAll quantitative assays have a lower LOD of at least 1,000 cp/mL; range for lower LOD is 25 cp/mL to 1,000 cp/mL. Additional AssaysMany of the platforms will have multiplex capabilities. Specimen TypeGenerally plasma for quantitative viral load; whole blood, capillary blood for qualitative assay or heelstick for EID Time to Result30 minutes to 5 hours; most assays take 60 to 90 minutes Cost/test – Range ($US)$3.00 to $15.00, but few data points Equipment Cost ($US)<$700 to ~$25,000

8. Conclusion A number EID and/or viral load platforms for use at or near the point of patient care are poised to enter the market this year and next. Implementation of these platforms at Level 1 facilities (health centers) will have the greatest impact on patient care as it is the level of the healthcare system at which most patients present. But, the ultimate effectiveness of testing will depend on the ability to deliver same-day results and linkage to care. Countries will need to think strategically about the appropriate mix of lab-based and POC testing for their particular needs, including the placement of tests designed for the POC or near POC.

9. Acknowledgements Thanks to UNITAID for funding my work on the HIV/AIDS Diagnostic Landscape.

10. Thank you