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

Evaluation: Time From Diagnosis To CD4 Staging And ART Initiation shows similar results in Uganda Conventional lab diagnostics do not fully meet patient needs; POC diagnostics can accelerate initiation/switching and reduce LTFU Uganda 1 Time to ART initiation: Reduced from 59 to 11 days Mozambique 3 LTFU: 50% reduction in loss to follow-up from diagnosis to ART initiation ART Initiation: 85% increase in ART initiation Malawi 2 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 Source: 1 MOH Uganda; 2 MOH Malawi; 3 Jani et al (2011) 2

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

Market Shaping Goals: 1)Creating healthy market competition and avoiding monopolies 2)Creating transparent systems for selecting products 3)Putting strong product-agnostic systems in place to allow easier product adoption 4)Ensuring long term sustainable prices 5)Planning for a sustainable transition The market shaping goals and public health goals of the project reinforce each other 4 In addition to improving access to diagnostics in the short term, this project will leave the market healthy in the long term Public Health Goals: 1)Appropriate uptake of POC to achieve improved access to high quality diagnostics 2)Earlier ART initiation, preservation of 1 st line ART, and timely switching to 2 nd line 1)Improved patient retention 2)Improved access to ART 3)Improved patient outcomes

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

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

New 2013 WHO Guidelines introduce several key changes, and will have significant impact on the Viral Load and CD4 markets 7 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 2 nd line ARVs, while others can preserve 1 st 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

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

We see 3 possible scenarios for the long-term CD4/VL need growth 9 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

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

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

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

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

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

Conclusions 15 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