Preventing HIV Drug Resistance with Programmatic Action Michael R. Jordan MD MPH

2 World Health Organization HIV Drug Resistance Surveillance and Monitoring Strategy  Successful scale-up of ART –Standardized, population based approaches –Inexpensive, generic, fixed dose combinations  Emergence of HIV drug resistance (HIVDR) is inevitable –High replication and mutation rate –Necessity for lifelong treatment

3 World Health Organization HIV Drug Resistance Surveillance and Monitoring Strategy  Universal access to ART accompanied by comprehensive global strategy to assess HIVDR  WHO in collaboration with HIVResNet is leading global HIVDR surveillance and monitoring efforts  WHO’s global HIVDR strategy provides actionable information for national ART programmes and clinics to support evidence-based recommendations at local, national and regional levels

Surveillance of Transmitted HIVDR in Recently Infected Populations Surveillance of HIVDR in Populations Initiating ART Surveillance of HIVDR in Children <18 months of Age Surveillance of Acquired HIVDR in Populations Receiving First- Line ART Monitoring of HIVDR Early Warning Indicators World Health Organization HIV Drug Resistance Surveillance and Monitoring Strategy

Surveillance of Transmitted Drug Resistance (TDR) in Recently Infected Populations Surveillance of HIVDR in Populations Initiating ART Surveillance of HIVDR in Children <18 months of Age Surveillance of Acquired HIVDR in Populations Receiving First- Line ART Monitoring of HIVDR Early Warning Indicators World Health Organization HIV Drug Resistance Surveillance and Monitoring Strategy

6 Early Warning Indicators of HIV Drug Resistance  WHO EWIs are quality of care indicators which assess factors associated with virological failure and emergence of HIVDR  Designed to be monitored at all ART clinics as part of routine monitoring and evaluation  Standardized definitions and targets  Results provide clinic specific information offering an opportunity for corrective action

7 WHO-recommended HIVDR EWIs ( ) EWIEWI Target 1. Prescribing practices100% 2. Lost to follow-up at 12 months≤ 20% 3. Retention on first-line ART at 12 months ≥ 70% 4. On-time drug pick up≥ 90% 5. On-time appointment keeping≥ 80% 6. Drug supply continuity100% 7. Viral load <1000 copies/ml at 12 months ≥ 70% Bennett DE et al., Antivir Ther 2008

8 50 countries; >2100 clinics; > patients

9 HIVDR EWI – Proportion of Clinics Achieving WHO- Recommended Targets Reports from 2107 clinics ( )

10 EWI Summary Although EWI methods are designed to provide representative data of national ART programme functioning, the small number of clinics reporting and non-representative sampling used by most countries preclude generalization of results  Available data indicate that adherence, procurement and supply distribution and retention remain important programme challenges

11 ART Programme Actions Resulting from EWI Monitoring Strengthened record keeping systems 1,2,3,4 Defaulter tracing initiatives to trace patients with unknown outcomes, support re-engagement into care and ART adherence 1,3 Procurement of funding from partners to scale-up EWI 5 Increase access to viral load testing 6 Routine review of patient pill pick-up and establishment of formal referral system to document transfers of care 3 1 Hong et al. JAIDS 2010; 2 Jack N et al. CID 2012; 3 Daonie et al. CID 2012; 4 Nhan DT el al. CID 2012; 5 Paula Mundari, Uganda National ART Programme, IAS 2010, Vienna; 6 Ye M et al. CID 2012

12 Important Lessons from the Field  Some EWIs more closely linked to HIVDR than others  Simplification of definitions, harmonization with other reported indicators, and revision of targets required  Integration into routine monitoring and evaluation necessary to achieve maximum benefit  Data abstraction and reporting should be delegated to ART clinics to foster ownership and local use of data

13 WHO HIVDR EWI 2012 Revisions  EWIs were evaluated using GRADE method for association with HIVDR and for optimal target  EWIs without strong association with HIVDR were eliminated  Each EWI retained evaluated –Minimize overlap of information obtained by each indicator –Maximize efficiency of data abstraction –Harmonize definitions with other reported indicators, whenever possible

HIVDR EWI Updates Package of 4 indicators each with one standardized definition and target grounded in available medical literature VL suppression at 12 months is “conditional” 5 th indicator but should only be monitored at clinics where VL testing is routinely performed on all patients 12 months after ART initiation New guidance on representative sampling of ART clinics Data abstraction reporting responsibilities delegated to ART clinics to foster ownership and local use of data Simplified scorecard reporting

Revised EWI Reporting: Scorecard Grey Red Amber Green Poor performance, below desired level Fair performance, progressing toward desired level Excellent performance, achieving desired level Data not available

Revised WHO HIVDR Early Warning Indicator Package Early Warning IndicatorTarget 1. On-time pill pick-up  Red: <80%  Amber: 80–90%  Green: >90% 2. Retention in care*  Red: <75% retained after 12 months of ART  Amber: 75–85% retained after 12 months of ART  Green: >85% retained after 12 months of ART 3. Pharmacy stock-outs  Red: <100% of a 12-month period with no stock-outs  Green: 100% of a 12-month period with no stock-outs 4. Dispensing practices  Red: >0% dispensing of mono- or dual therapy  Green: 0% dispensing of mono- or dual therapy 5. Viral load suppression at 12 months  Red: <70% viral load suppression after 12 months of ART  Amber: 70–85% viral load suppression after 12 months of ART  Green: >85% viral load suppression after 12 months of ART * Retention in care definition equal to UNGASS #24 and PEPFAR #T1.3.D

17 National level at-a-glance assessment of ART clinic performance Scorecard facilitates: Reporting of results Interpretation at clinic and national levels Strategic allocation of resources

18 WHO HIVDR EWI Conclusions (1)  Between 2004 and 2009, 50 countries monitored one or more EWI at select clinics  Although no global trends can be assessed, experiences show important gaps in service delivery and programme performance particularly with respect to fragility of drug procurement and supply systems and inadequate adherence and clinic retention

19 WHO HIVDR EWI Conclusions (2) EWI analyze routinely collected data through a drug resistance lens EWIs are the first line in preventing HIVDR  Routine monitoring of EWIs should be part of programme monitoring and evaluation and continuous quality improvement initiatives

20 WHO HIVDR EWI Conclusions (3)  EWI monitoring identifies weaknesses at ART clinic and programme levels associated with population-level emergence of HIVDR  Monitoring identifies clinics that can serve as best practice models to other clinics  2012 EWI revisions will facilitate uptake and integration into routine clinic practice

21 Acknowledgments  The Bill & Melinda Gates Foundation  Silvia Bertagnolio, WHO-Geneva  Diane Bennett, United States-CDC  Elliot Raizes, United States-CDC  Mark Myatt, Brixton Health, UK  Karen Kelley, PEPFAR  WHO HIVDR Early Warning Indicator Working Group  Neil Parkin, Data First Consulting  Countries, ART programmes and clinics reporting data