1. South Africa’s experiences and future plans for CD4 and viral load implementation
Lesley Scott
Department of Molecular Medicine and Haematology,
University of the Witwatersrand,
Johannesburg, South Africa
On behalf of the NHLS National Priority Program:
Wendy Stevens, Sergio Carmona, Debbie Glencross

2. NDoH Healthcare Facilities
Over 7636 health facilities
54 different categories of facility
45% urban, 45% rural, 0.7% peri-urban
Over 3515 ARV clinics
265 NHLS labs ~80% population (public sector)
National Department of Health manages health across all 9 provinces; provinces have significant autonomy
National Health Laboratory Service managed from a single headquarters in Johannesburg but services all 9 provinces: Services >80% of total public sector population
Responsible for teaching and research in pathology disciplines
National Footprint of 265 laboratories
Strong private sector with at least 5 major players services the insured population: knowledge base weak at a NDoH level on private sector activities
Universal testing for HIV and screening for TB – the primary objectives being to ensure that all citizens know their HIV and TB status, and to prevent new HIV and TB infections (NSP: ): massive increase in testing requirements

3. Scaling up Lab Capacity
HIV Specific Testing Volumes within the NHLS since 2006 has supported the growth # of patients on ART
Scaling up Lab Capacity
Forward planning with suppliers and funders
Pre-site assessments
Assess centralisation of lab services where possible
Pre-installation staff training (centralised) on both technical and Good Lab Practice
On site continued training
ID super users for on site troubleshooting
Distribution nationally of a prequalification panel and continued EQA programme (NHLS-QCMD partnership)
Vendor-Client monthly review committee to assess progress and preventative management

4. Laboratory services in South Africa
Total Population >50 Million: ~5.7Million HIV infected individuals.
20% worlds reported HIV‐associated TB cases and 4th largest reported numbers of MDR.
April 2012-April 2013: CD4 = 3, tests performed; VL = 1, tests, EID assays.
Changes to treatment guidelines
Once patient’s on ART, CD4 only performed at 12 months.
Pre-ART: CD4 every 6 months? (wellness clinic testing).
Estimated CD4 for 2013/2014:
14 million HCT – 2, (14%) expected HIV positive and require a CD4.
Target to initiate on ART, thus 1 CD4 at 12 months.
Residual 1, with CD4 >350c/ul will be monitored 6 monthly (ie 3, CD4 tests).
Total CD4 for 2013/14 = 6, : significant scale up
Universal testing for HIV and screening for TB – the primary objectives being to ensure that all citizens know their HIV and TB status, and to prevent new HIV and TB infections (NSP: 2012/ /2017) . Increase testing requirements
NSP,

5. NHLS consumes a large portion of the global HIV VL diagnostic supply, to minimize risks, 2 platforms are used for HIV viral load tesitng
Currently 17 functioning laboratories
8 sites using the Abbott m2000 system
9 sites using the Roche Cobas Ampliprep/ Cobas TaqMan system
Current instrument capacity (8 hour shift)
6888 samples per day = 151,536 per month = 1,818,432 per annum
Currently 2 HIV viral load systems as per tender agreement:
Abbott m2000 and Roche Cobas Ampliprep/Cobas TaqMan

6. Assay verification performed, internal and external Quality Control frequently lacking
South Africa’s NHLS rapid implementation/technology switch to the two testing platforms in 17 laboratories occurred within 8 months required:
Industry partner’s collaboration,
Training programs,
Method verification with a VL prequalification panel.
Material used to prepare the verification panels was a combination of known HIV-positive and -negative plasma packs (200 ml) obtained from the South African National Blood Services (SANBS):
42-member verification panel of 500 copies/ml, 2.7log copies/ml; 1,000 copies/ml, 3.0 log copies/ml; 5,000 copies/ml,3.7 log copies/ml; 50,000 copies/ml, 4.7 log copies/ml; and100,000 copies/ml, 5.0 log copies/ml).
The percentage similarity CV was useful as an overall measure of variability.
Across platform acceptable variability = 2.9% percentage similarity CV

7. Next Generation high throughput analysers: 2014: 3x current testing capacity
Modular with Medium to XL throughput
Continues sample loading
Random access
Increase testing menu: wider virology cover, microbiology and haem-onc
On board reagents (refrigerated >2wks) reducing hands on
Simple to run, one operator per 8 hr
Reduction of testing time 2-3hrs
~ 1000 HIV VL / 8hrs
? Cartridge based
Illustrative Only

8. Extending services: What can DBS provide?
With the improved universal access to ART, this would require adequate monitoring Dry Blood Spots (DBS) Provide a convenient alternative for specimen collection Transport logistics are simpler, with demonstrated stability vs blood tubes Collection of specimens may not require venisection but rather capillary blood Decentralisation of sample collection DBS may be used for infant diagnosis, VL monitoring and drug resistance testing Can be performed on several existing platforms, unclear on precision at critical range

9. Extending services: Plasma Preparation Tubes
Transport of blood samples without loss of RNA integrity
PPT centrifuged to separate cellular components from RNA.
The mean difference between EDTA and PPT prepared samples (n = 261) was acceptable (log 0.04 copies/ml, percentage similarity CV 3.53%).
PPT can be used for viral load testing on the CAP/CTM HIV-1 v2.0. Modificiations required for Abbott HIV-1 RT
But at an added cost!

10. The NHLS enumerates CD4 for the public sector at 62 labs – current footprint for >3.8m test
Red- NHLS CD4 lab
Blue- DoH clinic

11. Connectivity: interfaced to LIS Real time continuous
(currently 2 systems)
Real time continuous
monitoring through
middleware solutions

12. Centralised testing allows for central monitoring of operational aspects of VL, EID and CD4 testing: Dashboards
*connectivity of POC devices to a CDW imperative

13. Centralised testing allows for central data management and comprehensive M&E reporting: NDoH province, district….drill down
*connectivity of POC devices to a CDW imperative

14. Increasing access to results: SMS printers
SMS printers to improve turn-around-time of results back to facilities from the labs
Beneficial in remote, far-reaching areas where no internet access is available
SMS is automatically
generated from the lab’s LIS
Result printed on paper
and to be stored in patient’s
file
Initial roll-out in 2009:
Currently 1990 SMS printers in the field nationwide (~4500 DoH facilities)
Services available for: CD4 Count, HIV VL, EID, GeneXpert TB and TB Microscopy.
Dashboard

15. Totally Centralised model (4hr)
Models for POC implementation
Solution:
15 Labs
No POC
Decentralised model (1hr)
Solution:
127 Labs
190 POC
© Selective Analytics 2012

16. Proposed CD4 service delivery model to improve coverage
NHLS CD4 testing laboratories (Red),
Proposed community laboratories (Green),
POC/mini-lab sites (Yellow)
in reference to the NDOH clinics (blue)
Beckman Coulter, SP PLG incl. internal QC using bead flow rate.

17. Tiered CD4 service delivery plan within quality system (EQA)
True
POC
<10 samples/day
NHLS
Community laboratories
(outside of 200 km radius of
NHLS district laboratory)
Low Volume CD4 Instruments
>11<=100 samples/day
District laboratories
>100 <=300 samples per day
Centralized Testing Laboratories
>300 samples/day
Rural clinic , no ART
Testing for screening only : not for monitoring.
Patients go CD4 in hand to nearest HCT clinic.
LIS connectivity needed to ensure data captured
for patient follow-up and epidemiological review.
District HCT clinic
Possible enrolment onto ART or refer to nearest
treatment facility (locations identified by mapping
District HCT, ARV Referral Centres and NHLS
Community laboratories).
Instruments with higher precision/accuracy (>90%)
Connected to LIS. Do CD4 at baseline and for monitoring.
Increasing requirements for numbers of CD4 tests / day
All ARV treatment centers
Direct access to HCT
Referred patients
Screening and Monitoring
All ARV treatment centers
Direct access to HCT
Referred patients
Screening and Monitoring

18. Conclusions
The purpose of global ART: effective long-term treatment for all chronic patients (including paediatrics).
VL testing becoming more important for detecting VL failure and a move towards routine VL testing.
Level of access required for VL testing is most likely mixed model:
Centralised (super labs): easier to manage but requires good efficient logistics around specimen transport (ppt, DBS) and result reporting (sms printers)
Decentralized (POC): increase access, manage LTFU, consider: demand/ location/ throughput/ operator, must have connectivity
Implementation:
Clinical & Lab Service mapping including volumes critical
Equipment standardisation for costing
Pre-analytical and post-analytical remain problematic for different reasons
Careful costing, modelling, monitoring and evaluation of impact needed
Connectivity for national reporting critical

19. Acknowledgments National Department of Health
NHLS National Priority Program (Wendy Stevens, Sergio Carmona,
Debbie Glencross, Leigh Berrie, )
NHLS – CDW (Sue Candy)
NHLS POCT working group
Funders: Clinton Foundation, CDC, PEPFAR, Grand Challenges Canada, USAID
R&D Development team
HERO: Professor Sydney Rosen, Dr. Lawrence Long, Kate Schnippel, Bill Macleod
Connectivity working group (Brad Cunningham)