Preventing HIV Drug Resistance with Programmatic Action

Michael R. Jordan MD MPH

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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

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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

PopulationsSurveillance 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

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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

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WHO-recommended HIVDR EWIs (2004-2011)

EWI EWI Target

1. Prescribing practices 100%

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 continuity 100%7. Viral load <1000 copies/ml at 12 months

≥ 70%Bennett DE et al., Antivir Ther 2008

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Countries Implementing WHO HIV Drug Resistance EWI, 2004-2009

50 countries; >2100 clinics; >131 000 patients

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HIVDR EWI – Proportion of Clinics Achieving WHO-

Recommended Targets

Viral load suppression 12 months ≥70%

Drug supply continuity 100%

On time appointment keeping ≥80%

On time drug pick-up ≥90%

Retention on first-line ART ≥70%

Loss to follow-up ≤20%

Prescribing practices 100%

0% 20% 40% 60% 80% 100%

85%

65%

58%

17%

67%

69%

75%

Reports from 2107 clinics (2004-2009)

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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

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ART Programme Actions Resulting from EWI Monitoring

• Strengthened record keeping systems1,2,3,4

• Defaulter tracing initiatives to trace patients with unknown outcomes, support re-engagement into care and ART adherence1,3

• Procurement of funding from partners to scale-up EWI5

• Increase access to viral load testing6

• Routine review of patient pill pick-up and establishment of formal referral system to document transfers of care3

1Hong et al. JAIDS 2010; 2Jack N et al. CID 2012; 3Daonie et al. CID 2012; 4Nhan DT el al. CID 2012; 5Paula Mundari, Uganda National ART Programme, IAS 2010, Vienna; 6Ye M et al. CID 2012

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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

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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 possiblehttp://www.who.int/hiv/topics/drugresistance/en/index.html

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2012 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” 5th 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 reportinghttp://www.who.int/hiv/topics/drugresistance/en/index.html

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2012 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

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2012 Revised WHO HIVDR Early Warning Indicator Package

Early Warning Indicator Target

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

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National level at-a-glance assessment of ART clinic performance

Clinic EWI 1 On-time pill pick-up EWI 2 Retention EWI 3 Drug stock-outs EWI 4 Dispensing practices EWI 5 VL suppression1 95% 77% 100% 95% 95%2 70% 95% 100% 88% 98%3 100% 82% 75% 0% 75%4 85% …. 100% 0% 95%5 97% 60% 95% 0% 50%

…. …. …. ….. …. ….…. …. …. …. …. ….

100 100% 100% 100% 0% 100%

Scorecard facilitates: • Reporting of results• Interpretation at clinic and national levels• Strategic allocation of resources

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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

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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

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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

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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