Elliot Raizes, MD HIV Care and Treatment Branch AIDS 2012: WHO Satellite Symposium HIV Drug Resistance Surveillance and Control: A Global Concern July 22, 2012 The Future of HIV Drug Resistance Surveillance Division of Global HIV/AIDS Center for Global Health

Determining the Public Health Impact of HIVDR Surveillance  What do we need to know?  Trends in prevalence of HIVDR in select populations Recently infected Chronically infected (not on ART) On ART (acquired)  Patterns of HIVDR including prevalence of key drug resistance mutations (DRMs) Impact on future ART efficacy (1 st -line, 2 nd -line, PMTCT)  Risk factors for HIVDR (individual, programmatic)

Determining the Public Health Impact of HIVDR Surveillance  How will the information be used?  Modify ART regimens  Modify risk factors through programmatic improvements  Plan and implement follow-up surveys (possibly more detailed)  Improve monitoring systems (e.g., viral load)  Inform algorithms for routine genotyping At baseline At failure

HIVDR Surveys Described in the WHO Global Report  Transmitted Drug Resistance Surveys (TDR)  Prospective Monitoring Surveys  Early Warning Indicators Surveys (EWI)

Proposed Updated WHO HIVDR Surveillance Strategy Surveys of Transmitted Drug Resistance (TDR) in Recently Infected Populations Cross-sectional Survey of baseline HIVDR in adults initiating ART at representative sites Surveys of HIVDR in children <18 months of age newly diagnosed with HIV Cross-sectional Survey of acquired HIVDR in adults and children on ART for >12 months and >24 months at sentinel sites Monitoring of HIVDR Early Warning indicators

Public Health Impact and Feasibility of HIVDR Surveys  Transmitted Drug Resistance Surveys  Public Health Impact Trigger need for more comprehensive surveys Alert for suboptimal ART program function Inform regimen selection for PMTCT  Limitations Time to complete enrollment Definition of survey population may not be adequate proxy for recent infection Trends over time more difficult to assess when using thresholds Regional results informing national policy

Public Health Impact and Feasibility of HIVDR Surveys  TDR surveys: feasibility  73 surveys in 26 countries with classifiable results 69/73 performed before countries performed multiple surveys over several years  How recent does data need to be to correlate with programmatic quality or to affect policy change?  How rapidly can recommended public health actions be implemented?  TDR update  Definitions of recent infection modified

Public Health Impact and Feasibility of HIVDR Surveys  Early Warning Indicators Surveys  Public Health Impact Identify important gaps in service delivery and program performance Inform quality improvement projects at the site level  Limitations Need for harmonization with other program indicators Difficult to analyze global trends Challenge of choosing sites that reflect heterogeneity of program delivery models

Public Health Impact and Feasibility of HIVDR Surveys  Feasibility of EWI surveys  EWI 4 (on-time drug pickup): 321 clinics in Africa from *  Indicators measure overall quality of services as well as HIVDR risk To measure EWI: can use sentinel/representative sites to estimate national levels To improve EWI: number of sites needed to have national impact unclear  EWI Update  Reduced to five indicators (including 12 month viral suppression where available)  Goal is to incorporate into routine programmatic monitoring functions while still assuring that EWI will be collected and acted upon *WHO HIV Drug Resistance Report 2012

Proposed Updated WHO HIVDR Surveillance Strategy  Cross-sectional Survey of acquired HIVDR in adults and children on ART for >12 months and >24 months at sentinel sites Replaces prospective monitoring surveys as a core element o More rapid turnaround (≤ 3 months) o Yields more genotypes in failing patients o Selection of sites more representative o No country has achieved goal of implementing prospective survey at 15 sites in 3-year cycles Limitations o Cannot assess DRMs at baseline o More difficult to associate risk factors with acquired HIVDR Creates national dataset of HIVDR in patients failing ART at sentinel sites which can be updated every two years

Proposed Updated WHO HIVDR Surveillance Strategy  HIVDR in newly diagnosed HIV-infected children <18 months of age  Uses remnant specimens from EID program  Assesses HIVDR in children with or without exposure to PMTCT regimens  Results could impact both PMTCT regimens and pediatric ART

Cross-sectional survey of HIVDR in persons starting ART (Baseline HIVDR survey)  What is the prevalence of HIVDR in adults initiating ART?  Determining sampling plan: Confidence interval should be narrow enough to examine trends over time Sample size should be small enough to be able to collect data in a reasonably short period How many sites? o Larger sites preferred with geographic representation o Will lack of contribution of smaller sites influence results?

Cross-sectional Survey of baseline HIVDR in adults initiating ART at representative sites How will the information be used?  Modify empiric 1 st -line ART (or PMTCT) regimens  May need to determine threshold of prevalence of HIVDR at baseline  Catalyze expansion of capacity for viral load monitoring  Determine frequency/intensity of repeat surveys  Support new technology for pre-treatment screening for DRMs

Determining Priorities at the Country Level  Surveys should be repeated over specified time frame  Surveys should be interpreted by all stakeholders and appropriate public health actions taken where appropriate  Prevention of HIVDR should be the goal  Surveys should inform how well these prevention activities are working and where improvements are needed  Prioritization of decisions should not be limited to considerations of cost and capacity  HIVDR surveillance and prevention activities must be considered critical components of national ART programs  Investments may be needed to support capacity to perform priority surveys

Determining Priorities at the Global Level  Do we have the right structure(s) in place to generate useful data on Global HIV drug resistance?  2012 report with limited data (using WHO survey methodology) from Europe (East and West) and Western Hemisphere  What degree of harmonization of methodology is needed to inform global HIV guidelines?

Future of HIVDR Surveillance: Responding to Programmatic Shifts  Expansion of viral load capacity  Could 12 month viral load suppression become the only EWI?  Expansion of ART eligibility to asymptomatic populations may require special surveys and/or programmatic changes to maximize prevention of acquired HIVDR  Option B+  CD4 >350  Discordant Couples  High-risk transmitters  Test and Treat

Future of HIVDR Surveillance: Applying New Technology  Incidence assays to define populations of recently infected (for TDR surveys)  Detection of minor variants (pooled deep sequencing, allele-specific DR testing)  Confirm the extent of impact of minority variants on ART response in resource limited settings through ongoing research  Point-of-care resistance testing

Future of HIVDR Surveillance: Conclusions  Data from global HIVDR surveillance can continue to have major impact on public health policy  However, surveillance activity thus far has not kept pace with the rapid scale-up of ART coverage around the world, especially in resource-limited settings  Survey designs need to maximize public health impact but still be feasible for countries to perform  WHO’s evolving HIVDR surveillance strategy is an attempt to address ongoing programmatic shifts and new technologies  As countries continue to expand access to ART, HIVDR surveillance activities should be considered critical elements of national strategic planning

For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA Telephone, CDC-INFO ( )/TTY: Web: Thank You Center for Global Health Division of Global HIV/AIDS The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. PEPFAR HIVDR Subgroup CDC:USAID:NIH: John Aberle- Grasse Simon AgoloryTom MiniorKaty Godfrey Andrew Auld Diane BennettRobert FerrisJoe Fitzgibbon Debbi Birx Laura BroylesRyan PhelpsCarol Worrell Omotayo BoluHelen Dale Dennis EllenbergerTedd EllerbrockDOD:OGAC: Jon KaplanSurbhi ModiHelen ChunCharles Holmes Elliot RaizesMolly RivadeneiraLara Stabinski Chunfu YangJulia MacKenzie