Use of POC technologies for early diagnosis of HIV Francesca Celletti

What is innovation? Innovation is not only development of a product. It has to bring better values for clients and return from investments. The nature of the innovation should be of definable value, introduce a concrete change and bring about a related and measurable outcome What is missing here is what bring better life to people – better life is earlsy diahnos, early treatment and quality of treatment The world needs innovation on HIV and particularly on diagnostic to detect HIV early. The facts are telling.

Progress toward the target 57-81-82 Progress is promising. But we can see that the hardest 90 is the first. It is clear that better diagnostics are the solution. However, today we are here to talk about technological innovations, but the solutions to this issues is also programmatic.

Gaps in current early infant diagnosis cascade Challenge 1: Poor access to and delays in EID testing 51% of 1.2 million HIV-exposed African children had access to EID testing in 2014 Most HIV-exposed infants receive their first test at age 6 months or later (WHO recommends first test at 6 weeks) Challenge 2: Delays or no return of test results Median time of 30 to 90 days from sample to delivery of results Only 50% of children who are tested receive their test results Challenge 3: Poor initiation of HIV-positive infants on treatment SA study: 10 week delay between diagnosis and initiation of treatment Kenya study: 44% of HIV- positive infants never reached ART clinic 51% 50% Why do we need innovation? Can innovation improve prgrams> We need innovation that is close to hwer eteh business is. Hence the concepat of POC 8.9% 51% Source: On the Fast-Track to an AIDS-Free Generation, UNAIDS, 2016

Source: HIV/AIDS Diagnostics Technology Landscape, UNITAID, 2015 POC NAT pipeline ZIVA™ Cavidi 2015 2014 2016 SAMBA II EID DRW Kenya, Ugand, CE Markeda Alere™ q HIV-1/2 Detect Alere CE Mark Xpert® HIV-1 Qual Cepheid LYNX HIV p24 NWGHF Micronics Iquum/Roche Lumora Under development 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 Kenya, Uganda * Reported November 2015 - 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 GeneXpert Omni Cepheid Which innovation do we have? We need to be clear – it is different from what promised to us. Innovation we need to bold and blunt – there is a plan, an idea, but the results is different. There is a wastage, there might high risk – we need to facore that in in the programs and when intrdoucong innovation. Also, this is a presentation that focuses on the technology – but there is ino innavtion that is introduced to make a concrete Source: HIV/AIDS Diagnostics Technology Landscape, UNITAID, 2015 5

EGPAF/UNITAID POC EID project Goal: to increase the number of HIV-exposed infants whose HIV status is known and facilitate early initiation on treatment. Scale: 9 countries 4 years (2015 – 2019) $63 million Targets: 320,000 infants 13,562 HIV+ (4.2%) Results within 2 day EID coverage 20% ART initiation by 14 days Market shaping for POC To illustrate my statement, let me use as acase study the partnership with UNITAID. We have been in pediatric HIV for many years. We were failing to test and test eraly. It was clear to us the conevntioanl EID was not imotima. The program raised the need. How do we use it?

How is a product introduced and brought to scale in countries? R&D Entry into market Fit to needs Pre-qualification Pricing/negotiation Global forecasting In-country registration Fit for purpose Quality assurance Post-market surveillance Placement and delivery system Generation of demand Increase access Health workers training and acceptability Ensuring a market share UNITAID, 2016 Hence the partnership with UNITAID whose focus is to invest in innovation. The products has been in the market. Pre-Q came. We are now atrting implementation with the pilot in September. Impact and C/E evaluation Generation of new evidence Scalability Sustainability

Source: HIV/AIDS Diagnostics Technology Landscape, UNITAID, 2015 POC NAT pipeline ZIVA™ Cavidi 2015 2014 2016 SAMBA II EID DRW Kenya, Uganda Alere™ q HIV-1/2 Detect Alere CE Mark Xpert® HIV-1 Qual Cepheid LYNX HIV p24 NWGHF Micronics Iquum/Roche Lumora Under development 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 * Reported November 2015 - 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 GeneXpert Omni Cepheid We have a product – can this meet other needs? Source: HIV/AIDS Diagnostics Technology Landscape, UNITAID, 2015 8

Acute HIV infection AHI is primary stage, develops 2-4 weeks after infection RDTs miss this stage Population impact 5-50% of ongoing sexual transmission Up to 64% of vertical transmission Individual impact Intervention during AHI reduces viral set point Improved clinical outcomes (e.g. VISCONTI cohort) Key populations Pregnant women Older adolescent women Commercial sex workers Before initiating on PrEP Shanks PLoS One 2013; 2. Klarkowski PLoS One 2009; WHO 2015

National Testing Policies in Line with WHO Recommendations HIV infection Misdiagnosis Category # % Clerical/technical errors (e.g. mis-labelling, poor recordkeeping, clerical mistakes) 14 32% User error (e.g. errors performing RDT or interpreting results, misapplication of buffer, inaccurate reading time and other human errors) 11 48% Cross-reactivity (e.g. antibodies from inter-current infection, environmental exposure to test components, HIV subtype, or late-stage AIDS) 8 18% Incorrect / suboptimal testing strategy or algorithm (e.g. tiebreaker testing strategy) 22 50% Poor management and supervision (work load stress, staff shortages, lack of training, poor adherence to testing strategy or testing algorithm, substandard operating procedures, testing in window period) 20 45% National Testing Policies in Line with WHO Recommendations 48 Countries Review identified reports of misclassification range from 2.6% to 10.3%1,2 WHO 2015

Thank you