HIV Drug Resistance Monitoring in Malawi: Implementing prospective surveillance

1. HIV Drug Resistance Monitoring in Malawi:Implementing prospective surveillance Nellie Wadonda and Sara Hersey Malawi MoH and CDC Malawi 2nd Global HIV/AIDS Meeting Bangkok, Thailand

2. Overview • Background on ART and HIV Drug Resistance program in Malawi • Implementation of first round of prospective surveillance • Lessons learns in prospective patient monitoring • Training, implementation, supervision, recruitment, specimen quality, timeframe

3. Malawi has achieved rapid ART scale-up, but early mortality of people on treatment is high. HIV Prospective Drug Resistance Surveillance Sources:Routine ART monitoring, Malawi Ministry of Health, September 2008 HIV Sentinel Surveillance and Estimates and Projections, Malawi Ministry of Health, 2007

4. Malawi’s National Treatment Program • Approximately 50% coverage of those in need of treatment at 214 health facilities • Rapidly decentralizing • 95% on 1st line treatment (d4T/3TC/NVP), 5% on alternative 1st line, <1% on second line • Mortality of patients is 24% in first 12 months of treatment, 32% by 24 months and 40% by 36 months • Cumulatively, approximately 80% of people ever initiating treatment were identified through WHO clinical staging and 20% through CD4 counts • In the most recent ART monitoring quarter, treatment initiation by low CD4 rose to 24% and laboratory services are expanding

5. HIV Drug Resistance Surveillance in Malawi • Prospective surveillance (drug resistance prevention) • Threshold surveys • Early Warning Indicators • Retrospective survey found poor performance in DR programmatic indicators at some sites, particularly due to high loss to follow-up • LTFU decreasing with expanded, more accessible ART program

6. Objectives of prospective surveillance (1) • Estimate the proportion of the ART site population achieving ART drug prevention, as measured by viral load suppression, 12 months after starting first-line therapy • Genotype specimens to identify specific HIVDR mutations and mutation patterns in patients not achieving HIVDR prevention on first-line ART • Collect and analyze routine data on programmatic factors potentially associated with HIVDR

7. Objectives of prospective surveillance (2) 4. Report and disseminate results and recommendations in order to • Support optimal ART programmatic functioning at sentinel sites • Apply lessons learned to other ART sites 5. Identify further research needed on program factors associated with HIVDR and methods to optimize ART delivery 6. Support planning and decision-making to optimize ART effectiveness

8. Implementation of prospective surveillance • Three high volume central hospitals and one district hospital • 250-600 people started on ART/quarter • Longest standing ART sites in Malawi • All three regions represented • Sample size of 150/site • Accounting for transfers out and deaths • Low refusal rate when recruiting individuals • Group recruiting resulted in high refusals • Implemented by HIV Drug Resistance Task Force with diverse, active representation • Lead by Ministry of Health, Community Health Science Unit, epidemiology and laboratory

9. Data Collection Timeframe (January 2008-September 2009) Protocol development and clearance 2006-2007 January 2008 February 2008 April 2008 July 2008 July 2008 February 2009 September 2009 August 2008 July 2009 Central training Baseline (3 sites) Final site baseline completion Specimens for testing Database training Mid-term review and refresher training Outcome data collection (3 sites) Final site outcome completion Supervision & specimen centralization Supervision Supervision Supervision & specimen centralization Supervision Supervision

10. Data collection (1) • Baseline, follow-up and outcome data collected by short questionnaire • Administered by clinician • Monitored by on-site M&E staff and central supervisors • Implications for data quality and data entry • Variable electronic data collection systems at sites • Lack of national Electronic Data System and standards • Site-specific data collection systems implemented with differential quality

11. Data collection (2) • National ART program definition of “loss to follow-up” and adherence not per WHO HIVDR recommendation • WHO program LTFU: Not being seen for 3 months • No record for date of next visit • Doesn’t take into account whether patients was given 3 months of drugs • On-time drug pick-up not captured by Mastercard and no electronic pharmaceutical systems • Revising national ART data collection system • Date of next visit • Drug prescribing practices recording actual drug regimen (versus just 1st line, alt 1st line, 2nd line) • Discussions with EDS group on pharmaceutical monitoring system

12. Data collection form

13. Training, Monitoring and Supervision • Centralized training on protocol, informed consent, administering questionnaire, specimen collection and handling, quality control • Included Task Force, central supervisors, and management, clinical, laboratory and M&E staff from sites • Site-specific training • Management, clinical, laboratory and M&E • And re-training…. • Mid-survey refresher training • Lessons learned • Orientation on follow-up

14. Training, Monitoring and Supervision • Monitoring forms for recruitment, data collection and specimen collection and handling • Intensive supervision for baseline and early follow-up at start of recruitment • On-site review of monitoring findings including clinic supervisor and staff • “Quiet” supervision during follow-up • Determining appropriate level of surveillance team supervision • Potentially introducing bias by active involvement of surveillance team and marking files • However, required for high quality data

15. Monitoring recruitment and data collection • Early and intensive supervision of enrollment

16. Specimen collection and storage • Blood samples were drawn from eligible, consenting clients • Three government laboratories and one research lab • Variable “buy in” at different sites • Residual blood not used • Routine CD4s not done • When CD4s done, blood is drawn at least 2 weeks before start of ART • Would require spinning all potential samples and throwing out those not eligible • Extra cost and burden on laboratory staff to efficiently identify and store eligible plasma samples

17. Laboratory supervision • Early and consistent monitoring of specimen collection and handling

18. Monitoring specimen quality

19. Additional challenges • Integrating HIVDR surveillance into routine clinical and laboratory activities • Perception that it is a stand-alone research study • Coordinating clinic and laboratory involvement • Specimen tracking and storage • Different quality of care for people enrolled • Queue jumping • Not decentralizing patients to health facility based on standard practices • Positive: Patient tracing not done differently for participants and non-participants

20. Additional challenges • WHO recommendation to add 5-10 new sites per year and conduct second round of data collection at sites in the 4th year (=15-30 sites) • Malawi’s original plan: 6 additional sites added in 2009 (Karonga, Kasungu, Dedza, Machinga, Mulanje, Salima) with 6 new sites added each year until 22 sites reached • Recommendations for expansion of HIVDR surveillance: • 6 additional sites per year is not feasible • Need to determine feasible number and periodicity of data collection • Extend the original cohort to 24 months and beyond • Monitor decentralized catchement areas, private clinics, paediatric treatment

21. Acknowledgements • HIV Drug Resistance Task Force • Ministry of Health • Community Health Sciences Unit • HIV and AIDS Unit • World Health Organization • US Centers for Disease Control and Prevention, Malawi and Atlanta • Lighthouse Trust • Malawi College of Medicine • MSF France • University of North Carolina