Transcript HIV drug resistance surveillance: the need

Global HIV Drug Resistance
Surveillance Programme
Dr Stefano Lazzari
Coordinator
Risk Containment, Mapping and Drug Resistance (RMD)
Communicable Diseases Cluster
World Health Organization
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ARCS: Antimicrobial Resistance
Containment and Surveillance
Human/Animal
Infection
Antimicrobial
Drugs
Disease
Burden
Disease
Prevention
Diagnostics
Test Quality
Assurance
Prescribers
Behaviour
Consumer
Expectations &
Compliance
Appropriate
Treatment Regimens
Drug
Regulations
Essential
Drug Lists
Drug Approval
Systems
Consumers
Drug Delivery
Health Education
Systems
Regulatory
Framework
Procurement
Drug
Quality
Distribution/
Management
Rational Drug Use
Monitoring
Drug Use &
Selection
AMR Containment
Monitoring Drug Resistance
EPIDEMIC ALERT AND RESPONSE
Monitoring
Drug
Supplies
Milestones of the Programme

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
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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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Structure of the Programme
Steering Committee
WHO Secretariat
Epidemiology
HIVResNet
WG
ad hoc
Technical
Committee
Lab
WG
WG
Data use
WG
Data Management
WG
Technology transfer
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“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 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 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 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 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 (HIVResNet)
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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Secretariat
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 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
Resistance Surveillance
1.
2.
3.
4.
Introduction
Objectives and Intended Uses for Guidelines
Indicators and Definitions
Overview of Technical Issues
4.1. Epidemiology
4.2. Data Management
4.3. Quality Control
4.4. Laboratory Management including Quality Control
4.5. Implementation
4.6. Policy Development and Data Disseminatio
5. Annexes
5.1. Glossary of Terminology
6. References
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Key Public Health Questions

What is the level of resistance to ARV in circulating
HIV strains?
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How is HIV drug resistance changing over time?
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Does the level of HIV drug resistance justify/require
changes in preventive or treatment approaches?
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Which containment measures and/or treatment
regimens reduce/limit/slow down the emergence of
HIV drug resistance?
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Are current access to treatment programmes
causing a rapid increase in HIV resistance?
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Objectives of HIV drug resistance
surveillance

Assessing geographical and
temporal HIV drug resistance
prevalence
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Better understanding determinants
of resistance
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Identifying ways to minimize its
appearance, evolution and spread
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Populations 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)
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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 Populations

Persons newly diagnosed with HIV who never
received antiretroviral drugs
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Where possible, recently infected persons
– Detuned ELISA
– first pregnancy or age less 20/25 in ANC (?)
– Previous negative HIV test
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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 Epidemic
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VCT clinics
– access to ARV programmes
– preventive services for IDU, MSM, etc
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Centralized laboratories for confirmation of
HIV test, if available.
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Blood donors (if regular voluntary donations)
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Military recruit, STI patients, occupational
clinics
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Potential Sites for Generalized Epidemic
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High-volume VCT clinics
– access to ARV
– preventive services including PMTCT sites (<21 or
first pregnancy if possible)
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Centralized laboratories for confirmation of
HIV test, if available
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Blood donors (if regular voluntary donations)
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Military recruit, STI patients, occupational
clinics
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Patient Selection
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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%)
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Consecutive newly diagnosed persons meeting
inclusion criteria
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Periodicity: 2-3 years
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Start in urban areas with high ART access
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Sample collection
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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
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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 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
of HIV resistance surveillance

well-established public ART programme (more
than 3-5 years)
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at least 1% of estimated HIV infected individuals
on ART

at least 10% of people diagnosed with HIV have
been prescribed antiretroviral drugs
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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 issues

Cost of sequencing (currently around 200-300 US$)

Type of specimens (currently plasma at -80° but DBS are
being validated)
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Identifying recent HIV infections

Sequencing at national or supranational level
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Site selection and (representative?) sampling strategy

Pilot studies? LQA?
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