1. Cost effectiveness of rapid HIV and syphilis testing algorithms in antenatal care Claire C. Bristow, MSc Fielding School of Public Health University of California, Los Angeles Satellite Session Sunday July 20 th, 2014

2. What is a cost-effectiveness study? Economic analysis that compares relative costs and outcomes – In this case we’re looking rapid point-of-care HIV and syphilis testing algorithms

3. Why do we do cost-effectiveness studies? The concept of cost effectiveness is applied to resource allocation and management activities – Getting the most “bang for your buck” – Spending the least to gain the most – Using evidence to determine how to prioritize resources: “evidence-based public health”

4. Goals 1.To measure adverse pregnancy outcomes associated with alternative testing strategies 2.To measure the monetary costs of alternative testing strategies 3.To develop a cost-effectiveness model for policy-makers and implementers to determine the most cost-effective dual elimination strategy

5. We used Malawi as the base case for this analysis Option B+ start lifelong highly-active antiretroviral therapy at 14 weeks of gestation

6. 5 Testing Algorithms Dual rapid test for HIV and syphilis 1 single rapid test for HIV 1 single rapid test for syphilis HIV rapid test Lab-based TPPA/RPR for syphilis HIV rapid test only No Testing

7. Simulation Model 100,000 pregnant women in Malawi Followed through decision tree (testing pathway) and treatment, each step governed by probabilities Key inputs from data out of Malawi TreeAge Pro Software (Williamstown MA, USA)

8. Simulation Model Estimated expected adverse pregnancy outcomes based on each testing strategy – HIV mother-to-child transmission (MTCT) – Newborn syphilis infection – Prematurity/low birth weight – Neonatal death – Stillbirth

9. Decision Tree – Simulation model A schematic tree-shaped diagram used to show a statistical probability Each branch of the decision tree represents a possible event The tree structure shows how one choice or event leads to the next, and the use of branches indicates that each option is mutually exclusive

10. Decision tree - No testing No testing Proportion HIV uninfected Proportion of HIV uninfected women who are syphilis uninfected Proportion of these women with adverse pregnancy outcome Proportion of HIV uninfected women who are syphilis infected Proportion of these women with adverse pregnancy outcome Proportion HIV infected Proportion of HIV infected women who are syphilis uninfected Proportion of these women with adverse pregnancy outcome Proportion of HIV infected women who are syphilis infected Proportion of these women with adverse pregnancy outcome.106.9891.0109.894.978.022

11. One branch of the HIV rapid test only decision tree HIV rapid test algorithm Proportion of women receiving HIV rapid test HIV infected HIV test positive (test sensitivity) HIV treatment received Syphilis infected Pregnancy outcome Syphilis uninfected Pregnancy outcome HIV treatment LTFU …HIV test negative…HIV uninfected…Not tested…

12. COST EFFECTIVENESS ANALYSIS

13. Costs We considered costs of testing incurred by both the health system and the woman (labor costs determined using standard WHO health worker salaries for the region, patient travel costs, and test costs, etc.) We included costs of treatment for both syphilis and HIV infection in the pregnant woman and infant All costs were converted to 2012 US Dollars.

14. Effectiveness: Disability adjusted life years (DALYs) The disability adjusted life years (DALYs) is a measure of overall disease burden, expressed as the number of years lost due to ill-health, disability or early death DALYs were calculated using disability weights from the Global Burden of Disease study 1 A disability weight is a weight factor that reflects the severity of the disease on a scale from 0 (perfect health) to 1 (equivalent to death) DALYs were adjusted for co-infection 2 1.Lopez et al 2006 2. Owusu-Edusei et al 2014

15. DALYs The DALY metric is used to provide a single number to capture the health impact caused by a illness A DALY of 1 could represent 1 year of life lost (due to early death), 1.7 years spent with blindness, 5.2 episodes of malaria, etc. Syphilis infection in the infant has a disability weight of 0.315 per year and is estimated to last for 3 years. So a child born with congenital syphilis would receive a lifetime DALY value of 0.945

16. Incremental cost effectiveness ratio

17. Key inputs: epidemiology Cohort 10.6% HIV prevalence among pregnant women 1 – 24.8% of those with AIDS 2 1.09% syphilis prevalence among HIV- uninfected 1 2.2% syphilis prevalence among HIV-infected 1 1. Malawi Government 2012 2. Mwapasa 2006

18. Key inputs Test accuracy Sensitivity and specificity estimates were determined from literature review of field studies

19. Key inputs: Health system structure and use Treatment Option B+ for treatment of HIV infection Treatment for maternal syphilis infection with one injection (2.4 MU Benzathine Penicillin)

20. Key inputs: Costs Screening test costs $0.80 Single HIV rapid test $0.55 Single Syphilis rapid test $2.39 Syphilis laboratory tests (RPR/TPPA) 1 $1.30 Dual Rapid test – SD Duo® Patient costs Treatment costs for syphilis or HIV infection for life of infant Pregnancy outcome costs 1. Owusu-Edusei 2011

21. RESULTS

22. Expected adverse pregnancy outcomes per 100,000 pregnancies No testing program17,127 adverse outcomes HIV rapid testing only15,820 adverse outcomes HIV rapid testing and laboratory-based syphilis testing 15,779 adverse outcomes 1 single HIV and 1 single syphilis rapid testing 15,775 adverse outcomes Dual HIV/syphilis testing15,370 adverse outcomes

24. Summary results from the cohort decision model comparing the expected effects (DALYs) of the pregnancy and costs (2012 U.S. Dollars) for all 5 antenatal HIV and syphilis testing algorithms and a no-testing strategy in the Malawi setting. Total Program and Outcome Costs No testing $20,783,454 Dual HIV/syphilis $21,274,678 HIV test only $21,583,611 Single rapid tests for HIV & syphilis $21,593,145 HIV rapid test & RPR/TPPA for syphilis $21,605,356

25. Summary results from the cohort decision model comparing the expected effects (DALYs) of the pregnancy and costs (2012 U.S. Dollars) for all 5 antenatal HIV and syphilis testing algorithms and a no-testing strategy in the Malawi setting. Total Program and Outcome Costs DALYs No testing $20,783,454269,400 Dual HIV/syphilis $21,274,678228,829 HIV test only $21,583,611235,716 Single rapid tests for HIV & syphilis $21,593,145235,023 HIV rapid test & RPR/TPPA for syphilis $21,605,356235,094

26. Summary results from the cohort decision model comparing the expected effects (DALYs) of the pregnancy and costs (2012 U.S. Dollars) for all 5 antenatal HIV and syphilis testing algorithms and a no-testing strategy in the Malawi setting. Total Program and Outcome Costs Cost increase from no testing DALYS No testing $20,783,454 - 269,400 Dual HIV/syphilis $21,274,678$491,224228,829 HIV test only $21,583,611$800,158235,716 Single rapid tests for HIV & syphilis $21,593,145$809,692235,023 HIV rapid test & RPR/TPPA for syphilis $21,605,356$821,902235,094

27. Summary results from the cohort decision model comparing the expected effects (DALYs) of the pregnancy and costs (2012 U.S. Dollars) for all 5 antenatal HIV and syphilis testing algorithms and a no-testing strategy in the Malawi setting. Total Program and outcome Costs Cost increase from no testing DALYS DALYs prevented compared to no testing No testing $20,783,454 - 269,400- Dual HIV/syphilis $21,274,678$491,224228,82940,571 HIV test only $21,583,611$800,158235,71633,684 Single rapid tests for HIV & syphilis $21,593,145$809,692235,02334,377 HIV rapid test & RPR/TPPA for syphilis $21,605,356$821,902235,09434,306

28. Summary results from the cohort decision model comparing the expected effects (DALYs) of the pregnancy and costs (2012 U.S. Dollars) for all 5 antenatal HIV and syphilis testing algorithms and a no-testing strategy in the Malawi setting. Total Program and outcome Costs Cost increase from no testing DALYS DALYs prevented compared to no testing ICER* No testing $20,783,454 - 269,400- - Dual HIV/syphilis $21,274,678$491,224228,82940,571 12.11 HIV test only $21,583,611$800,158235,71633,684 Strictly dominated Single rapid tests for HIV & syphilis $21,593,145$809,692235,02334,377 Strictly dominated HIV rapid test & RPR/TPPA for syphilis $21,605,356$821,902235,09434,306 Strictly dominated *Incremental cost effectiveness ratio (ICER) is the ratio of the change in costs to incremental benefit of an algorithm.

29. Conclusions A dual HIV/syphilis testing algorithm in antenatal care would be the most effective means to reduce the number of adverse outcomes of pregnancy The dual point-of-care testing algorithm had lower overall costs and decreased life-time disability when compared to the other testing choices

30. Limitations Did not include procurement costs for tests or training costs Inputs are based on estimates from a variety of studies, actual measures may change over time This is a purely economic perspective, this doesn’t include the intangible values society places on pregnancy outcomes

31. Conclusions Integrating the screening of syphilis into antenatal HIV prevention programs through dual rapid point-of-care testing would increase the number of maternal infections detected and have the greatest impact on the prevention of HIV and syphilis related adverse pregnancy outcomes

32. Next steps, sensitivity analyses

33. Visit our posters! "Cost-effectiveness of dual HIV and syphilis testing“ - Thursday, 24 July 2014 from 12:30 - 14:30, Exhibition Hall, Ground Level THPE416 “Field evaluation of a dual rapid diagnostic test for HIV and syphilis in Lima Peru using SD BIOLINE HIV/Syphilis Duo“ - Wednesday, 23 July 2014 from 12:30 - 14:30, Exhibition Hall, Ground Level WEPE050

34. Acknowledgements Jeffrey Klausner, UCLA Elysia Larson, Harvard Thomas Gift, CDC Kwame Owusu-Edusei, CDC Lori Newman, WHO Fern Terris-Prestholt, LSHTM Peter Vickerman, Bristol University

35. THANK YOU Please get in touch if you want more information or have comments. ccbristow@ucla.edu Dualelimination.org