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: cdcinfo@cdc.gov 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