HIV Drug Resistance Monitoring in Malawi: Implementing by 3h3eq06L


									    HIV Drug Resistance Monitoring
              in Malawi:

         Implementing prospective

Nellie Wadonda and Sara Hersey
Malawi MoH and CDC Malawi
2nd Global HIV/AIDS Meeting
Bangkok, Thailand
• Background on ART and HIV Drug
  Resistance program in Malawi
• Implementation of first round of
  prospective surveillance
• Lessons learns in prospective patient
  – Training, implementation, supervision,
    recruitment, specimen quality, timeframe
                                Malawi has achieved rapid ART scale-up, but early
                                    mortality of people on treatment is high.

                                                        Cumulative patients on treatment

                                                    HIV Prospective Drug
                                                        Patients alive and on ART
      Number of people on treatment


                                                   Resistance Surveillance

                                      50000                                                     38817


                                                     2003                  2004                 2005                  2006            2007      2008 (Sept)

Sources:                                  Routine ART monitoring, Malawi Ministry of Health, September 2008
                                          HIV Sentinel Surveillance and Estimates and Projections, Malawi Ministry of Health, 2007
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
 HIV Drug Resistance Surveillance
            in Malawi
• Prospective surveillance (drug resistance
• 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
       Objectives of prospective
           surveillance (1)
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
2. Genotype specimens to identify specific
   HIVDR mutations and mutation patterns in
   patients not achieving HIVDR prevention on
   first-line ART
3. Collect and analyze routine data on
   programmatic factors potentially associated
   with HIVDR
       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
    Implementation of prospective
• Three high volume central hospitals and one district
   – 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
                                       Data Collection Timeframe
                                     (January 2008-September 2009)

Protocol development
    and clearance


January        February                April            July
                                                        July                    February                                   September
                                                                  August 2008                               July 2009
 2008            2008                  2008             2008                      2009                                       2009

                         Baseline                    Final site   Specimens                Outcome data                  Final site
                         (3 sites)                   baseline     for testing              collection                    outcome
                                                     completion                                                          completion
                                                                  Database                 (3 sites)
                                                                  review and
            Supervision Supervision Supervision
                                    & specimen
                                    centralization                              Supervision Supervision Supervision
                                                                                                        & specimen
           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
  – Implications for data quality and data entry

• Variable electronic data collection systems at
  – Lack of national Electronic Data System and
  – Site-specific data collection systems implemented
    with differential quality
              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
      • 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
Data collection form
         Training, Monitoring and
• 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
• Site-specific training
   – Management, clinical, laboratory and M&E
   – And re-training….
• Mid-survey refresher training
   – Lessons learned
   – Orientation on follow-up
         Training, Monitoring and
• 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
   – Potentially introducing bias by active involvement of
     surveillance team and marking files
   – However, required for high quality data
  Monitoring recruitment and data
• Early and intensive supervision of

  Supervision period: February 12-22, 2008

  Started on ART: 123
  Eligible for study: 95
  Enrolled in study: 58
  Refusals: Unknown (at least 3)
  Samples taken: 58
  Viable specimens: 58
  Eligible but not enrolled: 37 (13 from TB, 7 from PMTCT, 17 from ART)
  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
              Laboratory supervision
• Early and consistent monitoring of
  specimen collection and handling

 Samples in lab: 145
 Viable: 142
 One cryovial: (4) 047, 077, 081, 119
 Haemolysed: (3) 035, 047, 124
 Samples collected but missing: 058, 067, 101
 Samples not collected at all: 103, 105, 161
 Laboratory was not using the specimen transfer logs and hence there is missing
 information on date of collection, date and time of freeze. Some samples were labeled
 with accession numbers and some of them were managed to be traced their HIVDR IDs
 and were relabeled.
  Monitoring specimen quality
         Number of   Number of   Number       Number     Number sent
         people      samples     haemolysed   sent for   for testing
         enrolled    collected                testing    with
Site 1      150         150          0            150         0

Site 2      150         147          0            147         0

Site 3      150         146          4            142         1

Site 4      152         145          5            140         20

TOTAL       602         588          9            579         21
          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
          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
• 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

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