the future of hiv drug resistance surveillance
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The Future of HIV Drug Resistance Surveillance. 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. Division of Global HIV/AIDS. Center for Global Health. - PowerPoint PPT PresentationTRANSCRIPT
Elliot Raizes, MDHIV Care and Treatment Branch
AIDS 2012: WHO Satellite SymposiumHIV Drug Resistance Surveillance and Control: A Global
ConcernJuly 22, 2012
The Future of HIV Drug Resistance Surveillance
Division of Global HIV/AIDSCenter 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 (1st-line, 2nd-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 2010• 7 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
2004-2009* 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 elemento More rapid turnaround (≤ 3 months)o Yields more genotypes in failing patientso Selection of sites more representativeo No country has achieved goal of implementing
prospective survey at 15 sites in 3-year cycles• Limitations
o Cannot assess DRMs at baselineo 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 representationo 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 1st-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 Prevention1600 Clifton Road NE, Atlanta, GA 30333Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348E-mail: [email protected] Web: www.cdc.gov
Thank You
Center for Global HealthDivision 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 SubgroupCDC: USAID: NIH:John Aberle- Grasse Simon Agolory Tom Minior Katy GodfreyAndrew Auld Diane Bennett Robert Ferris Joe FitzgibbonDebbi Birx Laura Broyles Ryan Phelps Carol WorrellOmotayo Bolu Helen DaleDennis Ellenberger Tedd Ellerbrock DOD: OGAC:Jon Kaplan Surbhi Modi Helen ChunCharles HolmesElliot Raizes Molly Rivadeneira Lara StabinskiChunfu Yang Julia MacKenzie