The Future of HIV Diagnostics: Market Trends for CD4 and VL Testing

1. The Future of HIV Diagnostics: Market Trends for CD4 and VL Testing Decade of Diagnostics Satellite Kuala Lumpur July 2, 2013

2. Conventional lab diagnostics do not fully meet patient needs; POC diagnostics can accelerate initiation/switching and reduce LTFU Evaluation: Time From Diagnosis To CD4 Staging And ART Initiation shows similar results in Uganda • Uganda1 • Time to ART initiation: Reduced from 59 to 11 days • Malawi2 • PMTCT LTFU: PMTCT initiation during pregnancy increased from 51 to 78% • Time to CD4 result: Time from CD4 blood draw to result reduced from 11 to 0 days • Mozambique3 • LTFU: 50% reduction in loss to follow-up from diagnosis to ART initiation • ART Initiation: 85% increase in ART initiation Source: 1MOH Uganda; 2MOH Malawi; 3Jani et al (2011)

3. POC diagnostics project aims to expand access to POC HIV testing and improve patient outcomes: Earlier ART initiation, timely 2L switching Project Focus: 7 focus countries in East & Southern Africa Commodity Donation & Scale-up CD4, EID and Viral Load Market Preparation, Shaping Through programmatic work, project will partner with Ministries of Health to: Develop normative guidance on POC Testing Achieve regulatory approval for new products Facilitate uptake of new products The project will also work with suppliers to reduce pricing and accelerate market entry

4. The market shaping goals and public health goals of the project reinforce each other Public Health Goals: • Appropriate uptake of POC to achieve improved access to high quality diagnostics • Earlier ART initiation, preservation of 1st line ART, and timely switching to 2nd line • Improved patient retention • Improved access to ART • Improved patient outcomes Market Shaping Goals: • Creating healthy market competition and avoiding monopolies • Creating transparent systems for selecting products • Putting strong product-agnostic systems in place to allow easier product adoption • Ensuring long term sustainable prices • Planning for a sustainable transition In addition to improving access to diagnostics in the short term, this project will leave the market healthy in the long term

5. The project is working in 7 focus countries; each has made significant progress in POC CD4 implementation Ethiopia: Collaborating with CDC and other partners on site selection and training for 100 scale-up sites in 2013 Uganda: Operational study underway to improve clinic workflow and identify supporting interventions for 272 existing sites Kenya: Initial site selection and training plan finalized for 150 scale-up sites in 2013 Malawi: Site selection and training plan finalized for 83 scale-up sites in 2013, and connectivity rollout beginning Tanzania: Scale-up reached 445 sites in 2013, focusing on operational improvement through training and mentorship Zimbabwe: Scaling up connectivity to improve supply levels, quality assurance, and device maintenance for 276 existing sites Mozambique: Phased regional approach continuing to scale up from 157 to 207 sites throughout 2013

6. Existing POC CD4 is best suited for certain sites, but other future products may also be appropriate for different market segments Potential Test Volume 22% 15% 20% 19% 13% 11% Higher throughput devices Provincial Hospitals >70 District Hospitals 40-70 Large Clinics 20-40 Existing POC products are most appropriate in these settings Site CD4 Test Volume Per Day Medium Clinics 10-20 Small Clinics 5-10 VCTs, Health Posts, etc. <5 Low cost devices or device-free tests that can be deployed in very remote settings

7. New 2013 WHO Guidelines introduce several key changes, and will have significant impact on the Viral Load and CD4 markets • Viral Load • Strong recommendation for routine VL testing for all patients on ART, instead of only targeted use • More patients may be identified as failing treatment and eligible for 2nd line ARVs, while others can preserve 1st line • CD4 • All HIV+ adults with CD4 counts ≤500 cells/mm3 should start ART, regardless of clinical symptoms • More patients will be identified as eligible for ART In the long term, both of these changes will result in more demand for VL testing

8. While new GLs highlight “test and treat” for selected populations, CD4 will remain important to stage millions of patients 34m HIV+ people worldwide ~8m patients still not ART-eligible ~9m patients ART-eligible based on CD4 count Source: WHO presentation at ASLM Viral Load meeting, Cape Town, April 2013.

9. We see 3 possible scenarios for the long-term CD4/VL need growth • Scenario 1: Shift from CD4 to VL for ART monitoring following guidelines change • Scenario 2: VL for monitoring, CD4 to 500 for ART initiation drives significant shift from pre-ART patients to ART • Scenario 3: “Test and Treat”, gradual phase out of CD4 for initiation

10. Scenario 1: With new guidelines, VL need will increase significantly; however, countries may not move to CD4 500 threshold immediately Assumptions: • Routine VL for ART monitoring • No CD4 for ART monitoring after 2013 • 2 CD4 and 2 VL tests per year Tests (MM) New WHO Guidelines go into effect: Routine VL for ART monitoring

11. Scenario 2: If countries adopt new guidelines for both VL and CD4, existing CD4 testing volumes will shift to VL more quickly Assumptions: • Same as Scenario #1 • In addition, CD4 threshold to 500 for ART initiation Tests (MM) New WHO Guidelines go into effect: Routine VL for ART monitoring and CD4 500 for ART initiation

12. Scenario 3: WHO ultimately recommends a universal “Test and Treat” approach, resulting in gradual phase-out of CD4 for staging Assumptions: • Same as Scenario #2 • In addition, WHO recommends a universal “test and treat” approach in 2016 Tests (MM) WHO: “Test and Treat” New WHO Guidelines go into effect: Routine VL for ART monitoring and CD4 500 for ART initiation

13. Product agnostic systems for implementation will make transitions to future POC products and test types easier Product Selection Procurement/ Tendering Operator Training QA/QC 4 2 1 3 • Standardized sample collection • Systems training on clinic workflow • Sites participate in global EQA schemes • Other methods of QA in development • Objective selection criteria • Exclusion criteria to determine eligibility • Device rental to ease switching • Automatic volume discounts in tenders Patient Flow Data Analysis Mentoring/ Supervision Data Management/ Connectivity 5 8 6 7 • Tracking volumes for forecasting • Program mgmt with real time data • Regular site level follow up • Problem solving w/ real-time data • Referral between diagnosis and ART • Immediate treatment on CD4 • Open data systems to manage devices • Data transmitted remotely by modem

14. Introducing any new technology requires systems changes, but the coordination required to introduce VL will be even more significant Funding – Lab and 2L ARVs Guideline & Protocol __Changes Clinician & Patient Sensitization Training Health Workers S Systems Strengthening • POC CD4 experience can be leveraged to implement POC VL. For example: • Training and mentorship approaches • Quality assurance mechanism • Clinic workflow changes • Connectivity solutions

15. Conclusions • Early progress in POC CD4 has begun • The 2013 WHO guidelines will have a significant impact on the CD4 and VL markets • CD4 staging will remain instrumental in reaching the “15 by 15” target and beyond • Routine VL will increasingly be used for ART monitoring instead of CD4, but the shift will be gradual • POC VL implementation will build on the foundation of POC CD4, but there will be many additional challenges