1. The Pipeline for New HIV Diagnostics: The Promise and the Challenges
Maurine M. Murtagh
WHO-UNITAID Co-Hosted Satellite Event
AIDS 2012, XIX International AIDS Conference
Washington, DC
July 22, 2012

2. There are already several POC CD4 platforms on the market and more are coming
HumaCount CD4 NOW (formerly PointCare NOW), the Partec mini-CyFlow and the Alere Pima CD4 Test are already on the market.
The Alere Pima CD4 Test has been on the market since November In 2010, about ~650 devices were placed and ~580k tests sold; in 2011, this increased to ~1650 devices and ~900k – 1m tests sold; in 2012 through June, 750 analyzers have been placed, and 740k tests sold.
There are several other promising platforms on the horizon. These include the Daktari, mBio and BD platforms as well as disposables from Zyomyx and Omega Diagnostics. 2

3. CD4 Product Pipeline* Instruments BD Zyomyx mBio Daktari 2009 2010
Alere Pima CD4
HumaCount
mBio
Omega Diagnostics
Partec Mini
Daktari
2009
2010
2011
2012
2013
2014
Instruments
Disposable
*Estimated - timeline and sequence may change 3

4. Monitoring HIV Patients – Device- based POC CD4
Company
PointCare/Human
Partec
Alere
Daktari
Platform Name
HumaCount CD4 NOW
Partec CyFlow® mini POC
Alere Pima CD4 Test
Daktari™ CD4 Counter
Type
Desk top; ~26 lbs
Bench top portable; ~11 lbs
Bench top portable; ~5.5 lbs
Output
Absolute & %CD4, WBC, Hb, total lymphocytes
Absolute & %CD4, WBC, total lymphocytes
Absolute CD4
Specimen Type
40 µL venous blood
20 µL venous blood
16 µL fingerstick blood
Cost/test
~$10.00 per test, including controls
~$3.96 per test; high volume discounts
$ $12.00
~$8.00 per test; lower with volume discounts
Number of samples/run
~40 – 50 samples per day; TAT 8 minutes; no batching
Up to 250 tests/day; TAT 40 – 70 seconds per test after 15 minutes incubation
Maximum of ~20 samples per day; TAT 18 – 20 minutes per test
Equipment Cost ($US)
~$25,000
~$9,380; point-of-care package at lower effective cost
$6,500 to $12,000
~$1,000 4

5. Monitoring HIV Patients – Device-based and Disposable POC CD4
Company
MBio BD
Zyomyx
Omega Diagnostics/Burnet
Platform Name
Mbio CD4 System
BD Point of Care CD4 System
Zyomyx CD4 Counter
Omega Diagnostics CD4 Counter
Type
Bench top portable; ~6.6 lbs
Bench top; ~11 lbs
Disposable cartridge with mechanical mixer/spinner (less than 11 lbs)
Disposable cartridge with reader (~14 ounces)
Output
Absolute CD4
Absolute CD4, %CD4 & Hb
Specimen Type
10 µL fingerstick blood
16 µL fingerstick blood
100 µL fingerstick blood
40 µL fingerstick blood
Cost/test
TBD
<$8.00 per test
$2.00 per test estimated
Number of samples/run
~100 samples per day; TAT 20 minutes (17 minutes in cartridge; 3 minutes instrument reading)
Maximum of ~ samples per day; TAT 2- 5 minutes plus 20 minutes of incubation
~40 samples per day; TAT 10 minutes; batch processing TBD
~120 samples per day; TAT ~40 minutes, including incubation
Equipment Cost ($US)
~$200 for mixer/spinner; may be included in cost per test with TBD volume of test cartridges
~1,200 for reader, expected to go to $400 5

6. New Options for Viral Load Monitoring and EID are also on the Horizon
A number of new Viral Load/EID POC diagnostics are in development.
These will have lower instrument and per-test costs, but will also have lower throughput than lab-based systems.
One of these, the viral load assay for the Liat platform, may still launch in late 2012.
Additional platforms will follow over the next few years. 6

7. Technology Pipeline – Viral Load and EID*
Liat
Micronics
Alere Q
WAVE 80 EOSCAPE
ALL
Cavidi AMP
Lynx EID
SAMBA VL
SAMBA EID
Biohelix
Gene XPert
NWGHF VL
Lumora
2012
2013
2014
2015
2016 7

8. Monitoring HIV Patients on ART – Device-based Viral Load/EID
Company
IQuum
Alere
WAVE80
DRW
NWGHF
Platform Name
Liat™ Analyzer
Alere Q
WAVE80 EOSCAPE-HIV™ System
SAMBA Analyzer
Lynx
Type
Bench top portable; ~8.3 lbs
Bench top portable; <11 lbs
Bench top portable analyzer with separate processing units
TBD
Bench top portable processor unit with cartridge
Output
Quantitative or qualitative VL
Quantitative HIV-1 RNA
HIV-1 RNA
Semi-quantitative VL or Qualitative for EID
P24 antigen assay for EID
Specimen Type
200 µL plasma or µL fingerstick blood
25 µL fingerstick or 25 µL heel stick
100 µL fingerstick blood
200 µL plasma (VL) or 100 µL whole blood (EID)
~80 µL blood from infant’s heel
Cost/test
<$20 per test
~$7.00 to $15.00 per test
Number of samples/run
~ samples per day depending on LOD; TAT minutes, no batching
Max of ~10 samples per day; TAT 30 – 60 minutes
~50 samples per day with 6-8 processing units and a single analyzer; TAT 50 minutes; random access
4 samples per run; TAT ~90 to 120 minutes depending on assay
~16 samples per day; TAT 30 minutes (plus 10 minutes for blood draw and sample prep)
Equipment Cost ($US)
~$25,000, may be lower in LRS
~$10,000 for one analyzer with 2 processing units
~$400 - $700 8

9. What does it take for POC diagnostic technologies to be “game changers”?
There are some very promising POC diagnostics in the pipeline. In order for them to be “game changers”, they will need to help compensate for diagnostic system weaknesses in resource-limited settings:
Human Resources: Lack of trained staff, high turnover and insufficient training opportunities
Supply Chain: Ensuring the efficient and reliable supply of essential diagnostic products throughout the laboratory system is a significant obstacle to diagnostic delivery. Long and difficult transport of test reagents and consumables are the norm often under extreme temperature conditions, including temperature spikes.
Service/Maintenance: Lack of diagnostic equipment and frequent and prolonged breakdowns of equipment (lasting months and sometimes years)
Diagnostic Errors: Studies have shown that even for simple tests, quality-controlled and reproducible testing remains a major challenge in resource-limited settings; test errors are observed frequently. 9

10. Priority Characteristics of POC Diagnostics
In addition to strong technical performance and cost effectiveness, in-country research has demonstrated the following high priority characteristics for POC diagnostics:
Durability: device with no electronic or mechanical maintenance beyond simple tasks; rugged device that will tolerate high temperature tolerances and will tolerate shock and vibration; cartridges with long shelf life and ability to survive extreme temperature fluctuations and humidity; no cold chain or clean water required; battery back-up
Ease of use: simple sample preparation (few operator steps); ability to use unprocessed sample specimens; no operator intervention required during analysis; self-contained kits; little operator calibration; simple user interface and read-out
Training: test simple enough that its use can be explained to a healthcare worker in a day’s training or less; test simple enough to permit informal training among healthcare workers
Self-contained Quality Control: if device-based, device designed to cover a large number of quality issues rather than leaving them to staff: e.g., detecting expired kits (reject); detecting inadequate sample volume (reject); running process control 10

11. The Limitations of POC Testing
POC testing has the promise to fill gaps in access and capacity, and there are some exciting POC diagnostics either here or coming over the next few years. But, there is no silver bullet technology yet.
Understanding the realistic value and preparing for the implementation challenges is imperative to increase access to the right populations in the right way. 11

12. Acknowledgments UNITAID The Bill & Melinda Gates Foundation
Dr. Trevor Francis Peter
Advanced Liquid Logic, Alere, BD Biosciences, Biohelix, Burnet/Omega Diagnostics, Cavidi, Cepheid, Daktari Diagnostics, Diagnostics for the Real World, Human/PointCare, Iquum, Lumora, Mbio, Micronics, Northwestern Global Health Foundation, Partec, WAVE80 and Zyomyx 12

13. Thank you