1 © Cepheid Early Infant Diagnosis (EID): Strategies and Options © Cepheid Philippe JaconPhilippe Jacon President, Emerging MarketsPresident, Emerging Markets Durban, July 20 th 2016Durban, July 20 th 2016 CE-IVD. For in vitro diagnostic use outside of the United States. May not be available in all countries

2 © Cepheid Source: 2015 Progress report on the Global Plan UNAIDS / JC 2774/1/E New paediatric HIV infections reduced by 60% since 2009, in 21 priority countries Final risk of HIV transmission to children drops from 40% to 5% among breastfeeding women in four countries, and in eight other countries transmission has reduced to below 10% 80% of pregnant or breastfeeding women living with HIV accessed antiretroviral medicines and 93% are accessing lifelong antiretroviral therapy Half the children living with HIV (51%) are now accessing treatment, compared to 15% in 2009 Good Progress in Preventing Mother to Child Transmission

3 © Cepheid In 2015, 110,000 children were newly infected with HIV in 21 countries, with 150,000 worldwide. Only 50% of HIV-exposed infants received EID in the first 2 months Access to EID for Exposed Infants has Improved but Coverage Remains Low Source: GARPR data UNAIDS UNICEF WHO, UN Declaration. political-declaration-HIV-AIDS_en.pdf

4 © Cepheid Overall the number of EID tests performed has grown from ~200,000 in 2007 to almost 1,000,000 in 2014 Conventional Central Laboratory Diagnostic Strategies Alone Will Not Achieve Goals by 2020 Source: CHAI annual lab data requests; government reports; UNAIDS data; Global Plan; CHAI-UNICEF Pediatric Project Grant Reports

5 © Cepheid Close to 50% of mothers/ caregivers never receive results Sample transport to centralised testing facilities is difficult and expensive Results turnaround times are too long, up to 90 days Retention is poor across the testing to treatment cascade Dried Blood Spot (DBS) quality may be compromised Challenges of EID from the Experience of Scaling Up Over the Past Decade Source: Global AIDS Response Progress Report, WHO, Geneva 2015, Chatterjee et al. BMC Public Health, 2011

6 © Cepheid 1 HIV Diagnosis 2 Enrollment in HIV care 3 Blood draw 4 Test performed 5 Result received 6 Clinical consultation 7 7 ART initiation 8 8 Monitoring Point of Care is key in expanding access to actionable results, reduce loss and improve patient outcomes for both mother and child nd line (when necessary POC HIV - Mother POC VL – Mother & Child POC VL/EID – Mother & Child Same day testing to baseline plasma VL resultSame day EID to ART initiation Point of Care Decentralization Will Transform the Continuum of Care for Both Mother and Child Source: Lehe et al (2014).

7 © Cepheid Innovation and technology alone will not address all the gaps Products need to be accessible at reasonable prices, adapted to specific country contexts, and integrated effectively into health systems Additional entry points for EID must be considered to increase PMTCT coverage, i.e. immunization clinics, maternity wards (testing at birth), pediatric TB clinics Health care workers on the ground need to well-trained on how to use new technologies and sample preparation Supportive environment for integrating these new technologies into existing health systems must be created through the adoption of national and global policy recommendations Infants who are diagnosed need to be promptly linked to treatment Gaps & Challenges

8 © Cepheid EID TechnologiesEID Technologies

9 © Cepheid WHO Prequalification: Xpert ® HIV-1 Qual and Alere™ q HIV-1/2 Detect “These tests mark a significant breakthrough in our response to HIV in young children. They are simpler, faster, automated platforms that do not require as much infrastructure as the conventional lab-based systems and can be used at or near the point of care.” Mike Ward – WHO Essential Medicines and Health Products” Source: WHO. July 2016

10 © Cepheid Xpert ® HIV-1 Qual: Whole Blood & DBS Workflow Whole Blood Collect ≥100 µl whole blood and transfer to EDTA microtainer tube or lavender tube Use the 1mL pipette to transfer 0.75 mL sample reagent into sample chamber Use the transfer pipette to transfer 100 µl whole blood into sample chamber Scan cartridge barcodeLoad into GX and close door Time to Result in GeneXpert = 90 min OR Dried Blood Spot Collect DBS with µl whole blood per spot Transfer 1 DBS into the sample reagent bottle and mix. Incubate in Thermomixer at 56°C, 500 rpm for 15 min Transfer all liquid into sample chamber with the 1 mL transfer pipette Scan cartridge barcode Load into GX and close door Source: Cepheid Xpert HIV-1 Qual Package Insert.

11 © Cepheid Simultaneously Perform POC Testing At Birth and Measure Mothers’ HIV Viral Load for Baseline Viral Load or to Measure ART Adherence Polyvalent Systems May Improve Mother and Child Outcomes AttributeXpert® HIV-1 Viral LoadXpert® HIV-1 Qual Intended Use Quantitation: HIV-1 VL Monitoring Qualitative: HIV-1 detection Sample TypePlasma: EDTA and ACDWhole Blood or DBS Subtypes HIV-1 Group M subtypes A, B, C, D, AE, F, G, H, AB, AG, J, K and Group N and Group O HIV-1 Group M subtypes A, C, D, F, G, H, CRF AG/GH, A/E and A/B, Group N and Group O Sample Input Volume 1 mL plasma 100 uL of whole blood or 1 DBS (60-70 uL of whole blood) Limited of Detection EDTA Plasma: WHO: 18.3 cp/mL, VQA: 15.3 cp/mL Whole Blood: VQA: 203 cp/mL, WHO: 278 cp/mL DBS: VQA: 531 cp/mL, WHO: 668 cp/mL Limited of Quantification 40 copies/mLN/A Linear Range 40 – 10,000,000 HIV-1 RNA copies/mL N/A TAT90 minutes92 minutes Hands On Time <1 minute <1 minute (WB) <3 minutes (DBS) Source: Cepheid Xpert HIV-1 Qual and Xpert HIV-1 Viral Load Package Inserts.

12 © Cepheid ZIVA™ Cavidi Technologies: Available and Pipeline* SAMBA II EID DRW Kenya, Uganda Alere™ q HIV-1/2 Detect Alere CE Mark Xpert® HIV-1 Qual Cepheid CE Mark LYNX HIV p24 NWGHF Micronics Iquum/Roche Lumora Omni QuantumDx Ustar DFA TaqMan® HIV-1 Qual v2.0 Roche DBS CE Mark RealTime Qual HIV-1 Abbott DBS CE Mark (2011) SAMBA I Semi-Q EID DRW Kenya, Uganda * Reported November timeline and sequence may change no specific market launch date; DBS assay CE Mark noted for laboratory products ** In addition, open polyvalent platforms are currently available for HIV VL and EID testing Source: Global AIDS Response Progress Report, WHO, Geneva 2015, Chatterjee et al. BMC Public Health, 2011

13 © Cepheid Global Commitments to EID and PMTCT

14 © Cepheid Commitment for Infants: EGPAF UNITAID- Funded Program EGPAF is implementing a UNITAID-funded project to optimise early infant diagnosis of HIV in nine African countries through the introduction of new- to-market, point-of-care HIV testing. The project aspires to increase the number of infants with HIV receiving lifesaving treatment, while also developing robust global and national markets for affordable, effective and equitable HIV infant testing Source:

15 © Cepheid Commitment for Vulnerable Patient Groups Especially Women A super fast-track framework for ending aids in children, Adolescents and young women by 2020 In agreeing to the Sustainable Development Goals, the global community set an ambitious target of ending the AIDS epidemic by To reach this target, children, adolescents and young women need a super fast-track approach to access HIV prevention, treatment, care and support services. This approach holds the potential to end the AIDS epidemic among children, adolescents and young women by UNAIDS + PEPFAR + Partners: Start Free, Stay Free, AIDS Free Source:

16 © Cepheid WHO: HIV Treatment & Care Highlights: 1.Anti-Retroviral Therapy (ART) initiation for all 2.Innovative approaches such as POCT and adding NAT at birth can speed up identification and ART initiation for infants 3.Routine viral load at 6 and 12 months and every 12 months there after if the patient is stable on ART 4.Plasma specimens are preferred for VL testing though DBS is recommended for use in limited resource settings Source:

17 © Cepheid Two Primary Goals of the WHO Recommendation to Add Birth Testing to the EID Algorithm 1.To increase access to infant diagnosis by opening up a new potential entry point for testing and reducing the coverage gap (the first loss point in the treatment cascade) 2.To improve the chances that infected infants are started on ART early, before the period of high early mortality

18 © Cepheid Conclusions POC decentralization with polyvalent technologies is key to improving patient outcomes and meeting the 90:90:90 targets Plasma-based POC HIV Viral Load technologies should be used as they become available versus DBS HIV Viral Load Countries and donors need to work together towards integrating and improving the efficiency of HIV and TB programs on a polyvalent POC molecular based system

19 © Cepheid Visit us at us at Thank You.Thank You. © Cepheid 19

20 © Cepheid WHO PQ Performance: Xpert ® HIV-1 Qual Sample Input: 100 µl of Whole Blood or 1 Dried Blood Spot (DBS) 00_XpertQualHIV_v2.pdf?ua=1

21 © Cepheid WHO PQ Performance: Alere™ q HIV-1/2 Detect Sample Input: 25μL capillary or venous blood 00AlereHIVDetect_v2.pdf?ua=1

22 © Cepheid Balance in the Healthcare System is Critical to Improve Patient Outcomes and Cost Effectiveness