Cost effective implementation of POC molecular testing and the impact on a priority population: EID and beyond

HIV Infections Among Infants Is a Public Health Emergency Early infant diagnosis of HIV (EID) is vital to ensure HIV-infected infants begin lifesaving treatment as early as possible, thereby ensuring their survival The WHO recommends early testing of all HIV-exposed infants, rapid return of results, and prompt antiretroviral treatment (ART) initiation for those who are HIV-positive All HIV-exposed infants should have a virological test at four to six weeks of age or at the earliest opportunity thereafter (strong recommendation)1 The turnaround time (TAT) from specimen collection to results return to caregiver should never be longer than four weeks. (strong recommendation)2 Positive test results should be fast-tracked to the mother-baby pair as soon as possible to enable prompt initiation of ART, if needed (strong recommendation)1 Point-of-care early infant HIV diagnosis (POC EID) can be used for early infant HIV testing (conditional recommendation)2 POC EID testing can be used to confirm positive test results3 Consideration can now be given to replacing RDT at nine months with NAT (e.g. POC EID)3 1 World Health Organization (2016). Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Second edition. Geneva. 2 World Health Organization (2010). WHO recommendations on the diagnosis of HIV infection in infants and children. Geneva. 3 World Health Organization (2018). Technical report. HIV diagnosis and ARV use in HIV-exposed infants: A programmatic update. Geneva.

With laboratory-based EID testing, the number of steps from sample collection to return of results to caregiver and clinical action lead to persistent delays and a high proportion of lost results. Step 1 Specimen collection at health facility Step 2 Sample transport to laboratory Step 3 Analysis at the laboratory Step 4 Result return to health facility When presenting, I suggest mentioning practices that contribute to long TAT, such as batching of DBS cards at health facilities and labs. Additionally, note that the time between steps 4 & 5 (the return of the result to the patient) can be quite long. Step 5 Result return to caregiver Timeframe: 30-90 days

Why POC EID? Challenges with the Conventional EID Cascade Turnaround time from blood sample collection to return of results to caregiver: 30-90 days We have three main challenges affecting EID in sub-Saharan Africa: Poor access to and delays in EID testing – this is affecting our ability to reach the first 90 - the ability to diagnose HIV Delays or no return of test results. Within the literature, the median turnaround time between sample collection and results received is anywhere between 30-90 days. This TAT is critical because of the consequences of delayed return of results and treatment initiation: 20% of perinatally infected infants will die by 2 months of age  increasing to 35% by 12 months  to 50% by age 2 if untreated. Greatest loss of mother-baby pairs occur due to delays in return of results to the caregiver. Longer the TAT, decreased likelihood of ART initiation. 3. If infants are not getting their test results back, we face challenge # 3: Poor treatment initiation for HIV+ infants. This affects the second 90 and ultimately the third 90 around treatment and VL suppression. With early diagnosis and treatment, we can reduce early infant mortality and HIV disease progression by 76% and 75%, respectively. Source: On the Fast-Track to an AIDS-Free Generation, UNAIDS, 2016

With Conventional EID Testing Many Infants Never Get Results Based on a weighted average of nine studies and monitoring and evaluation (M&E) data, 42% of EID test results are not received by the patient Wasted reagents Wasted HR time Unnecessary repeat testing Infants LTFU before receiving results Poor linkage between testing and care and treatment High infant mortality

Results from Implementation Study in 9 Countries: Conventional vs Results from Implementation Study in 9 Countries: Conventional vs. POC EID (Cameroon, Cote d’Ivoire, Eswatini, Kenya, Lesotho, Mozambique, Rwanda, Zambia, Zimbabwe)   Conventional EID (N=102 sites, n=3082 tests) POC EID (N=1574 sites, n=126,789 tests) p value Median TAT from blood sample collection to result returned to caregiver (IQR) 50 days (31-71s) 0 days (0-1 ) p<0.001 Results received by caregiver within 30 days 19.2 % 96.9% Percent of HIV-infected infants started on ART within 60 days of sample collection 41.5% (44/106)  92.2% (3990/4327) Median TAT from blood sample collection to ART initiation for HIV-infected infants (IQR) 50 days (30-68) 0 days (0-1)

Cost Per Test Result Returned Current conventional reagents are approximately $10, while the price of POC EID cartridges range from $14.90 to $25. BUT what truly matters is cost per test result returned so clinical action can be taken (and time and resources not wasted). Conventional POC (current throughput) POC (optimal throughput) Cost per result returned in 30 days (range) $131.02 USD ($96.26-$165.76) $37.89 USD ($32.54-$43.25) $27.24 USD ($21.39-$33.10) Cost per result returned in 3 months (range) $38.89 USD ($28.57-$49.21) $37.51 USD ($32.21-$42.81) $26.97 USD ($21.17-$32.76) When doing our cost per test analysis, we considered that the cost per test result received was a closer measure of the true value of a diagnostic. We can’t just consider the cost of the test itself because if the test result is not received, it’s wasted resources and cannot impact clinical decision-making. Cost per result received was calculated using The Global Fund to Fight AIDS, Tuberculosis and Malaria’s total cost of ownership (TCO) estimates for both POC and conventional EID. An average TCO was calculated for the most commonly used conventional EID products (Roche and Abbott conventional analyzers) and the POC EID products used in this project. As the TCO is dependent on instrument throughput, for POC EID, we calculated the TCO based on our current throughput (up to 3 EID/day) and an optimal throughput as estimated by the Global Fund (approximately 70% of platform capacity). The average TCO for conventional and POC EID were then divided by the average percentage of results returned to caregiver for the respective EID testing modality. *https://www.theglobalfund.org/media/5765/psm_viralloadearlyinfantdiagnosis_content_en.pdf

ICER vs conventional for year of life saved: $630 USD Cost-effectiveness modeling for Zimbabwe found POC EID improved survival by 6.8% in the first 3 months of life and was cost-effective compared to Conventional EID. ICER vs conventional for year of life saved: $630 USD Frank et al. LHIV 2019.

The incremental cost-effectiveness ratio (ICER) for POC EID is $630 per year of life saved. This is $740 less per year of life save than Option B+ for PMTCT, which is a widely accepted and used intervention. .

Meeting the diagnostic needs of the patient Where they present Integrated Diagnostics: Moving Closer to the Goal of Patient-Centered Care Meeting the diagnostic needs of the patient Where they present Accurately In a holistic way With rapid clinical action Integrated diagnostics adapted to the facility type, patient population and site set-up Ensuring HCWs have the tools and training to support integrated testing With fidelity Safely for the patient and provider

DTG vs EFV When Starting ART in Late Pregnancy Rapid Response to Viremia in Pregnancy: An opportunity to improve PMTCT DTG vs EFV When Starting ART in Late Pregnancy Viremia at Delivery by Regimen Khoo S et al. CROI 2019 Seattle, WA Abs. 40LB

Closer to EMTCT: Plans for POC VL in Lesotho

Conclusions: POC EID Is a Game-Changer Early HIV testing, prompt return of test results, and rapid initiation of treatment reduce morbidity and mortality among HIV-infected infants. HIV-exposed infants have a right to a timely and accurate diagnosis POC resulted in significantly improved EID outcomes when compared with conventional EID: Dramatically reduced turnaround time for test results (median of 50 days with conventional testing versus 0 days with POC) Twice as likely for HIV+ infants to be initiated on treatment in 60 days POC EID is cost-effective and saves lives It is critical that diagnostics are valued in public health if we are to reach our goals Diagnostic integration offers the opportunity to provide patient-centered care and also improve platform utilization, thus improving value for money First multi-country evaluation using routine testing data collected within MOH structures. POC would be a valuable tool to include within existing EID networks.

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