Global HIV Drug Resistance Surveillance Programme

1. Global HIV Drug Resistance Surveillance Programme Dr Stefano Lazzari Coordinator Risk Containment, Mapping and Drug Resistance (RMD) Communicable Diseases Cluster World Health Organization

2. Disease Drug Prevention Regulations Essential Test Quality Drug Lists Assurance Drug Approval Appropriate Systems Treatment Regimens Consumers Drug Delivery Health Education Systems Rational Drug Use Monitoring Monitoring AMR Containment Drug Use & Drug Selection Supplies Monitoring Drug Resistance ARCS: Antimicrobial Resistance Containment and Surveillance Human/Animal Antimicrobial Infection Drugs Regulatory Disease Framework Burden Procurement Diagnostics Prescribers Drug Behaviour Quality Consumer Distribution/ Expectations & Management Compliance EPIDEMIC ALERT AND RESPONSE

3. 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 • 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

4. Steering Committee WHO Secretariat Epidemiology HIVResNet WG ad hoc Technical Committee WG Lab WG Data use WG WG Technology transfer Data Management Structure of the Programme

5. “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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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.

14. Outline of Guidelines on ARV Drug Resistance Surveillance • 1. Introduction • 2. Objectives and Intended Uses for Guidelines • 3. Indicators and Definitions • 4. 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

15. Key Public Health Questions • 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?

16. Objectives of HIV drug resistance surveillance • Assessing geographical and temporal HIV drug resistance prevalence • Better understanding determinants of resistance • Identifying ways to minimize its appearance, evolution and spread

17. 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) • 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

18. Proposed 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)

19. Potential 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

20. Potential 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

21. Patient 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

22. Sample 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) • attime of treatment (pregnant women only) • possibility to draw sample • difficult moment for collecting epi/clinical info

23. 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

24. Suggested options for the initiation 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

27. Unresolved 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?