E P I D E M I C A L E R T A N D R E S P O N S EE P I D E M I C A L E R T A N D R E S P O N S E

Global HIV Drug Resistance Surveillance Programme

Dr Stefano LazzariCoordinator Risk Containment, Mapping and Drug Resistance (RMD)Communicable Diseases ClusterWorld Health Organization

EPIDEMIC ALERT AND RESPONSE

AntimicrobialDrugs

Human/AnimalInfection

ConsumerExpectations &Compliance

PrescribersBehaviour

RegulatoryFramework

Distribution/Management

DrugQuality

Procurement

DiseaseBurden

Monitoring DrugSuppliesMonitoring Drug Resistance

MonitoringDrug Use &Selection

ARCS: Antimicrobial ResistanceContainment and Surveillance

Diagnostics

Treatment Regimens

ConsumersHealth Education

DiseasePrevention

Appropriate

Test QualityAssurance

AMR Containment

Rational Drug Use

Drug DeliverySystems

DrugRegulations

EssentialDrug Lists

Drug ApprovalSystems

E P I D E M I C A L E R T A N D R E S P O N S E

First Consultation on Monitoring the Emergence of Antiretroviral Resistance, Rome, October 2000

First Draft workplan of WHO HIV Drug Resistance Surveillance Programme, February 2002

The Global HIV Drug Resistance Surveillance Programme launched, Barcelona, July 2002

Final workplan of WHO HIV Drug Resistance Surveillance Programme, November 2002

Meeting of Task Force Members, Boston, February 2003

Meeting of European Task Force Members, Luxembourg, March 2003

Meeting of Working Group 1 (Surveillance) in Oslo, 25-26 April 2003

Meeting of Steering Committee, Paris, 12 July 2003

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Milestones of the ProgrammeMilestones of the Programme

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Structure of the ProgrammeStructure of the Programme

Steering Committee

ad hoc Technical Committee

WG

WG

WG

WG

WG

HIVResNet

WHO Secretariat

Epidemiology

Data use

Technology transferData Management

Lab

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““Steering Committee”Steering Committee”

Functions– Provide direction to the Programme

– Coordinate activities

– Develop global strategy for monitoring

– Approve operational guidelines, workplans and budgets

– Review progress and suggest new directions

– Set criteria for membership of technical working groups

– Suggest country level priorities

Meet at least twice yearly

Hold regular conference calls between meetings

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Steering CommitteeSteering Committee

Suggested Members– WHO

– IAS

– CDC

– Euro-SPREAD

– ANRS

– Representatives from Asia, Latin America and Africa with operational and scientific expertise (3 total)

– Major donors/foundations (1-3)

– Community representatives (2)

– Representative of Scientific Coordinating Committee

Appointed by WHO

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Ad Hoc Scientific CommitteeAd Hoc Scientific Committee

Role– Coordinate and provide oversight to working groups

– Respond to scientific and operational questions

Functions– Ensure Working Group productivity

– Review guidelines and other documents produced by the working groups

– Ensure development of tools for planning and needs assessments

– Support to the Secretariat in providing expertise and technical support to participating countries

– Assist in developing tools for monitoring of the Programme

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Ad Hoc Scientific CommitteeAd Hoc Scientific Committee

Members– Chairs and Vice Chairs of Working Groups

– Population sampling expert

– Data management specialist

– Biostatistician

– Modeling expert

– Ethics expert

– Others, depending on emerging needs

Selected by WHO in consultation with the Steering Committee

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Working GroupsWorking Groups

Proposed and operative– Surveillance operations and design

– Data management and analysis

– Laboratory, quality control and monitoring

– Capacity building, technology transfer and training

– Policies and data dissemination

Roles/functions outlined in Plan of Action document

New WGs will be established as need arises

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Operational Network (Operational Network (HIVResNetHIVResNet))

Global network of laboratories and surveillance sites

Participation open to all countries interested

Sites may be designated as National HIV Drug Resistance Surveillance Sites – responsibilities:– Assess local needs

– Suggest revisions in the protocols to suit local requirements

– Liaise with Secretariat for operational needs and training

– Facilitate implementation of surveillance studies

– Provide data to the HIVResNet Data Management Centre

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SecretariatSecretariat

Hosted at the WHO

Functions– Provide technical and administrative support to the Programme

– Manage and coordinate the network

– Ensure quality and timeliness of plans and products

– Ensure dissemination of protocols, guidelines and data through website and other mechanisms

– Facilitate needs assessments, regional training and technology transfer

– Coordinate efforts with other WHO departments and regional offices

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Progress to DateProgress to Date

WHO/IAS Endorsement

WHO Secretariat established with 2 Professional staff

Draft Action Plan

Data base support and structure developed.

Phase I Pilot Study Completed, Phase II ongoing

Global Fund resolution

Draft surveillance guidelines being developed.

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Outline of Guidelines on ARV Drug Outline of Guidelines on ARV Drug Resistance SurveillanceResistance Surveillance

1. Introduction2. Objectives and Intended Uses for Guidelines3. Indicators and Definitions4. Overview of Technical Issues

4.1. Epidemiology4.2. Data Management4.3. Quality Control4.4. Laboratory Management including Quality Control4.5. Implementation4.6. Policy Development and Data Disseminatio

5. Annexes5.1. Glossary of Terminology

6. References

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What is the level of resistance to ARV in circulating HIV strains?

How is HIV drug resistance changing over time?

Does the level of HIV drug resistance justify/require changes in preventive or treatment approaches?

Which containment measures and/or treatment regimens reduce/limit/slow down the emergence of HIV drug resistance?

Are current access to treatment programmes causing a rapid increase in HIV resistance?

Key Public Health QuestionsKey Public Health Questions

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Objectives of HIV drug resistance Objectives of HIV drug resistance surveillancesurveillance

Assessing geographical and temporal HIV drug resistance prevalence

Better understanding determinants of resistance

Identifying ways to minimize its appearance, evolution and spread

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Populations of interestPopulations of interest

Persons newly diagnosed with HIV and not previously exposed to antiretroviral drugs

– Newly diagnosed and recently infected with HIV

– Newly diagnosed with established HIV infections

Persons about to begin their first antiretroviral drug regimen (not yet exposed)

Persons receiving antiretroviral drugs for treatment of HIV infection

– First antiretroviral drug regimen (tested after 6 or 12 months)

– Second antiretroviral drug regimen or a subsequent regimen.

• Persons whose previous treatment has not failed, but whose treatment has been switched for other reasons

• Persons whose previous regimen(s) was/were changed because of treatment failure

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Proposed Target PopulationsProposed Target Populations

Persons newly diagnosed with HIV who never received antiretroviral drugs

Where possible, recently infected persons– Detuned ELISA

– first pregnancy or age less 20/25 in ANC (?)

– Previous negative HIV test

Treated population will not be targeted for surveillance though specific studies may be required (e.g. proportion of failures due to resistance)

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Potential Sites for Concentrated EpidemicPotential Sites for Concentrated Epidemic

VCT clinics

– access to ARV programmes

– preventive services for IDU, MSM, etc

Centralized laboratories for confirmation of HIV test, if available.

Blood donors (if regular voluntary donations)

Military recruit, STI patients, occupational clinics

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Potential Sites for Generalized EpidemicPotential Sites for Generalized Epidemic

High-volume VCT clinics

– access to ARV

– preventive services including PMTCT sites (<21 or first pregnancy if possible)

Centralized laboratories for confirmation of HIV test, if available

Blood donors (if regular voluntary donations)

Military recruit, STI patients, occupational clinics

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Patient SelectionPatient Selection

Sample size: around 400-500 sequences (sufficient to determine if resistance prevalence is less that 5% or to detect difference/change from 5% to 10%)

Consecutive newly diagnosed persons meeting inclusion criteria

Periodicity: 2-3 years

Start in urban areas with high ART access

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Sample collectionSample collection

At the same time of HIV diagnostic test – limited epi/clin information, ethical issues regarding consent

– need to store all samples. test only when HIV-positive results come back

when giving back HIV test results to patients– epi/clinical information usually available– need to collect extra sample– informed consent is usually required (difficult time for asking consent)

at time of treatment (pregnant women only)– possibility to draw sample– difficult moment for collecting epi/clinical info

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Additional InformationAdditional Information

Unique subject and site identifier

ART history (if yes--exclude)

Previous HIV test (+/-)

Age group

Date of blood draw for resistance testing

No consensus on: Age/date of birth, gender, area of residence, date of previous negative HIV test, evidence of recent infection, clinical stage, CD4, risk factors

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Suggested options for the initiation Suggested options for the initiation of HIV resistance surveillance of HIV resistance surveillance

well-established public ART programme (more than 3-5 years)

at least 1% of estimated HIV infected individuals on ART

at least 10% of people diagnosed with HIV have been prescribed antiretroviral drugs

a well-designed pilot study or subsequent sentinel site surveillance has detected a prevalence of drug resistance of > 5% among newly diagnosed individuals with HIV in one or more sites

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Unresolved issuesUnresolved issues

Cost of sequencing (currently around 200-300 US$)

Type of specimens (currently plasma at -80° but DBS are being validated)

Identifying recent HIV infections

Sequencing at national or supranational level

Site selection and (representative?) sampling strategy

Pilot studies? LQA?