The WHO HIV Drug Resistance Strategy Presented by Dr. Don Sutherland Prepared by: Dr. Don Sutherland Dr Silvia Bertagnolio Dr Diane Bennett HIV Drug Resistance Team CAR/HIV Department World Health Organization

Steering Committee Technical Committee WG HIVResNet WHO Secretariat Epidemiology, Statistics: Protocols, HIVDR database Clinical program Support: HIVDR monitoring at sentinel sites Global Laboratory Network: The World Health Organization has brought together WHO HIVResNet, a global group of experts, laboratories, and organizations to develop methods for and support or HIV drug resistance (HIVDR) prevention, surveillance, and monitoring as antiretroviral treatment (ART) is rolled out worldwide. Working groups Country HIVDR Committees HIVDR monitoring & surveys WG HIVDR Information Exchange

WHO HIVDR Essential Package Goal Background: l The emergence of HIV drug resistance is inevitable, given HIV's high mutation rate and the need for lifelong treatment. l In countries with years of ART experience, – a high percentage of treated individuals have resistant HIV, and – transmitted resistance to some drugs and drug classes is reported in 5%-20% of newly infected drug naïve persons WHO HIVDR Goal: To support ART program practices, and country planning, to minimize the unnecessary emergence of HIV drug resistance, and to restrict the extent to which resistance jeopardizes the effectiveness of the limited ART regimens available, within the context of the national HIV prevention and treatment plan

The Country HIVDR Package National HIVDR strategy elements for countries scaling up ART The Country HIVDR Package National HIVDR strategy elements for countries scaling up ART A. Development of a national HIVDR strategy working group, plan and budget B. HIVDR prevention activities C. Regular evaluation of HIVDR "early warning" indicators from all ART treatment sites D. HIVDR transmission threshold surveys: geographic areas, populations, timing E. Sentinel monitoring of HIVDR emerging in treated populations and related ART programme factors F. HIVDR database development G. A designated HIVDR genotyping laboratory H. Preparation of national annual HIVDR report and recommendations

A. HIVDR working group l Formation of a national HIVDR working group within the Ministry of Health or National AIDS Program –Development of terms of reference –Integration of HIVDR strategy into country ART plan l Workplan –Implementation of the essential HIVDR package/plan/budget –Data analyses and interpretation –Regular collection, reporting, and dissemination of annual reports –Annual HIVDR Report -evidence-based recommendations for public health action Optimize national ART programme functioning Appropriate section of standard ART regimens, prophylaxis –Partnerships for all aspects of the work

B. HIVDR Prevention l Standard prescribing practices: highly active ART regimens l Quality assurance for drugs l Adequate and continuous drug supplies; monitoring l Standard treatment records; patient and cohort monitoring l Support for and monitoring of adherence l Removal of barriers to continuous access to care l Prevention programs to reduce HIV transmission from persons in treatment l Surveys of transmitted drug resistance l Monitoring of HIVDR emergence in treatment and related ART program factors in sentinel clinics l Evaluation of relevant ART program factors for HIVDR prevention in all ART clinics

C. HIVDR Early Warning Indicators C. HIVDR Early Warning Indicators l WHO recommends that the national HIVDR working group collect a group of 7 indicators from all ART sites throughout the country to inform prevention of HIVDR on a population basis –Examples: prescribing practices, ART drug delivery interruptions, ART drop out rates l The working group produces an annual summary of information from the early warning indicators analysis and can offer site specific recommendations on HIVDR prevention, surveillance and monitoring activities for the following year.

Early Warning Indicator 2: prescribing practice siteN initiating ART first QTR 2006 N prescribed regimens other than according to National ART Guidelines % standard PuHo % PuHo % PuHo % PuHo % PuHo % PHU % PR % PR %

D. Using the WHO/HIVResNet HIVDR threshold survey to assess transmitted resistance l Requires 47 or fewer specimens from recently infected persons sequentially diagnosed in a geographic area –Utilizes sequential HIV diagnostic specimens from HIV serosurveys in antenatal clinics, voluntary counselling and testing centres, or other HIV diagnostic settings l Inclusion: – Ideal: All persons recently infected with HIV – Practical: Newly diagnosed persons likely to have been recently infected l Allows area-specific classification of transmitted HIVDR to individual drugs and drug classes as 15% for specific geographic areas l HIVDR prevalence classifications trigger specific recommendations for action by HIVDR working group

A minimum-resource, sentinel-site-based strategy for monitoring prevention of HIVDR during the first year of treatment, and the factors associated with HIVDR emergence l Perform HIVDR monitoring at sentinel clinics representing major clinic types in diverse areas of the country l Evaluate ART program factors associated with HIVDR prevention / emergence of specific resistance patterns l Address factors of concern in sentinel clinics; apply “lessons learned” to other clinical settings E. Strategy for Monitoring of HIVDR Emerging in Treatment

Protocol summary for Monitoring of HIVDR emerging in treatment and related ART program factors l Cohorts beginning ART followed for 12 months (may extend to 24) l Genotyping of residual specimens at baseline, and viral load plus genotyping at 12 months or at regimen switch l HIVDR outcome measures: –HIVDR prevention (defined as viral load suppression) –HIVDR mutations evaluated if viral load is detectable l Potentially associated factors measured include; previous ARV experience, baseline mutations, prescribing practices, adherence, drug supply continuity –Sentinel site program factors associated with resistance could be evaluated in other clinics –Sentinel site "prevalence of resistance" is not nationally representative

HIVDR Assessment using HIVDR Early Warning Indicators from all ART sites and HIVDR sentinel Monitoring in Malawi

F. HIVDR database development 1. Database application supplied by WHO, will be customized for use in each country Modules 1.-HIVDR Surveillance 2.-Monitoring 3.-Genotyping results-linked to surveillance and monitoring modules, Additional features: -Customized reports can be produced -Selected data items can contribute to the WHO HIVResNet regional and global databases

National HIVDR Database - Data Flow HIVDR Transmission Surveillance Eligible recently infected individuals HIVDR Monitoring of ART Programs Eligible new ART patients National Genotyping Laboratory HIVDR Country Report Viral Load Lab National HIVDR DATABASE HIVDR transmission surveillance module Monitoring of HIVDR emerging in ART module Genotyping results module Laboratory Specimens Demographic, Clinical Data Laboratory Data Results and analysis Relevant ART Program, treatment, prevention indicators HIVDR research studies

G. Designate a HIVDR testing laboratory l One or more genotyping laboratories meeting WHO criteria to be selected by the Ministry of Health for HIVDR surveillance and monitoring specimen genotyping l Two options: –Local laboratory meeting WHO HIVResNet accreditation criteria –WHO accredited Regional laboratory from the WHO/HIVResNet HIVDR Lab Network l Technical assistance and training can be provided by the WHO HIVResNet network to support in-country laboratory development to achieve accreditation l Assessment visits and genotyping of quality assurance panels regularly assure continued standardization of results globally

H. Preparation of national annual HIVDR report and recommendations l Any statement/publication regarding HIVDR in must be reviewed and approved by W/G l Annual HIVDR Report is Key activity of National HIVDR Working Group l Used to report on: – HIVDR situation –contributing factors –recommendations for ART and HIV prevention program adjustments and plans for implementation of recommendations –Surveillance and monitoring planning for the following year l Can contribute to Regional and Global HIVDR annual report

Swaziland HIV Drug Resistance (HIVDR) Country Plan 2006/7 Is HIV Drug Resistance occurring in Swaziland during the ART scale up? Is HIV Drug Resistance 'spreading like wildfire' in Swaziland? The following is a proposal for Swaziland to assess the situation and make recommendations to the National ART and HIV Prevention program