Ruanne V. Barnabas1, Paul Revill2, Nicholas Tan1, Andrew Phillips3 WEAD0206LB Cost-effectiveness of routine Viral Load Monitoring in LMICs: A Systematic Review Ruanne V. Barnabas1, Paul Revill2, Nicholas Tan1, Andrew Phillips3 1University of Washington, Seattle, USA, 2University of York, York, UK, 3University College London, London, UK

Conflict of Interest No conflicts of interest to declare

Outline Background Methods Results Discussion

Background Routine viral load (VL) monitoring - WHO recommendation for HIV monitoring. VL testing – substantial cost Under what conditions are health gains from viral load monitoring at a cost such that it is cost-effective? What can we learn from previous studies? Hypothesis: Key features of program design and delivery costs drive the cost-effectiveness of viral load monitoring

Determining cost-effectiveness Health benefits from VL monitoring should be greater than those forgone due to limited resources being unavailable for other priorities Requires comparing the cost-per-DALY-averted from VL monitoring with a cost-effectiveness threshold

Methods Systematic review of studies on the cost-effectiveness of viral load monitoring in LMICs Broad search for VL and cost/economics PubMed, EMBASE, conference abstracts Inclusion criteria: CEA for VL monitoring, LMIC Cochrane Collaboration guidelines and PRISMA reporting guidelines Results synthesized qualitatively into themes

Results 1,165 unique results  23 reviewed  18 met inclusion criteria Settings: SSA, Cameroon, Uganda, South Africa, Zambia, Zimbabwe, Cote d’Ivoire, Vietnam, Thailand between 2001-2035 2 RCT1,2 and 16 modeling analyses 12/18 studies concluded that VL monitoring is cost-effective Both cost effectiveness analyses from RCTs1,2 did not find VL to be cost-effective ICERs varied widely from $68,084/QALY gained3 to $326/DALY averted4 1Boyer et. al., LID, 2013 (Cameroon); 2Kahn et. al., BMJ, 2011 (Uganda); 3Schneider et. al, AIDS, 2011; 4Phillips, et. al., Nature, 2015

1) Heterogeneity in results due to: Variation in health care resources available/setting Until recently, lack of consensus on appropriate cost effectiveness threshold for a given setting Cost of VL testing ($6 - $104 per test) (variation in whether the cost was fully loaded) Annual cost of ART ($108 - $2,071 per client) Cost range due to agreements with manufacturers, volume of demand, advocacy, human resource costs, calendar time

Heterogeneity in results due to: E.g. Keebler: Annual VL vs. VL every 36 months: Braithwaite (20 years): $6,018.83 per DALY averted HIV Synthesis (15 years): $3,413.8 per DALY averted Estill (5 years): $3,760 per DALY averted Some models did not include the benefits of decreased transmission (as a health benefit) Due to the heterogeneity, we were not able to estimate a summary statistic

Discussion We found 3 main factors that make it more likely for viral load monitoring to be cost-effective in a given setting using an appropriate CE threshold: Use of effective but lower cost approaches Ensuring the viral load results are acted upon Viral suppression supports less intense clinical care (differentiated care)

1) Use of effective but lower cost approaches 2014 – ceiling price for VL test - $9.40 ($20 fully loaded) Downstream costs are important: Second line ART – PI - $205 ppy (from $600) Including lower cost VL monitoring and ART changes ICER Cote d’Ivoire: ICER $4,100  <1,500/ YLS* *Ouattara, et. al. CID, 2016

2) Action based on viral load results VL test  lab  result back to client and provider  change to 2nd line ART if needed Protocols can support clinical next steps (adherence counseling, 2nd line ART) Evidence is needed for criteria to switch to 2nd line ART including confirmatory viral load testing POC VL test – real-time response Many models assume immediate/3 month time frame for switch to second line – needed for health benefits Caution: <5% of HIV+ people are on 2nd line therapy

3) Differentiated care for HIV Client-centered differentiated service delivery (DSD) simplifies care for HIV+ persons: Visit spacing, replacing CD4 with VL monitoring, community-based ART, longer prescription refills, task-shifting, DBS specimens, using clinical care resources for complex cases and persons not suppressed on ART VL testing is the key to doing this – knowing who can be seen less often - cost of VL testing is offset by clinical savings VL testing indicates individual and program effectiveness

DSD for HIV in Zimbabwe Phillips, A, et. al. Nature, 2015

Looking ahead Integrase inhibitors – higher barrier to resistance – possibly decreased clinical benefits of VL testing Alternative monitoring (TAF/TDF in urine) Need to reassess cost effectiveness as new ART and models of care are rolled out

Conclusions Cost-effectiveness of VL monitoring – context dependent DSD needs to be scaled up – cost savings support VL monitoring Data on viral suppression and costs – standard, routine collection can support scale up of successful differentiated care strategies

Thank you rbarnaba@uw.edu We are grateful to all the wonderful authors who responded to our questions as part of the systematic review Nick Tan Nicholas Tan U. of Washington Paul Revill U. of York Andrew Phillips UCL Funding: #OPP1134599