Transcript The Future of HIV Drug Resistance Surveillance

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
Center for Global Health
Division of Global HIV/AIDS
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
Monitoring of
HIVDR Early
Warning indicators
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
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 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 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
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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
Thank You
PEPFAR HIVDR Subgroup
CDC:
John Aberle- Grasse
Andrew Auld
Debbi Birx
Omotayo Bolu
Dennis Ellenberger
Jon Kaplan
Elliot Raizes
Chunfu Yang
Simon Agolory
Diane Bennett
Laura Broyles
Helen Dale
Tedd Ellerbrock
Surbhi Modi
Molly Rivadeneira
USAID:
Tom Minior
Robert Ferris
Ryan Phelps
NIH:
Katy Godfrey
Joe Fitzgibbon
Carol Worrell
DOD:
Helen Chun
OGAC:
Charles Holmes
Lara Stabinski
Julia MacKenzie
For more information please contact Centers for Disease Control and Prevention
1600 Clifton Road NE, Atlanta, GA 30333
Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348
E-mail: [email protected]
Web: www.cdc.gov
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.
Center for Global Health
Division of Global HIV/AIDS