Simplification, cost-reduction strategies and examples from the
field Teri Roberts
Diagnostics AdvisorMSF Access Campaign
Virological Monitoring Detects Treatment Failure Early On
Adapted from Bartlett et al. Lancet Infect Dis 2009
Across programmes: 2% of treated patients are on 2nd-line ARTIn South Africa (Khayelitsha), where routine virological monitoring is available: 12% on 2nd-line after 5 years
HIV Policy and Progress Indicators Across 16 CountriesCameroon CAR DRC Ethiopia Guinea India
VL for Tx failure
OPT OPT OPT NO OPT REQ
Routine VL OPT NO NO NO NO NO
Available LTD LTD LTD LTD LTD LTD
Kenya Lesotho Malawi Mozambique Myanmar
VL for Tx failure
OPT OPT REQ OPT OPT
Routine VL NO NO NO REQ NO
Available YES LTD LTD NO LTD
South Africa Swaziland Uganda Zambia Zimbabwe
VL for Tx failure
REQ OPT OPT OPT OPT
Routine VL REQ NO OPT OPT NO
Available YES LTD LTD LTD LTDLynch et al. Science 2012OPT: optional; REQ: required; LTD: limited
How to increase access to virological monitoring?
• Reduce complexity• Reduce price
– Market entry– Volume– Competition– Open and polyvalent platforms– Price transparency
• Field validate new and current tests (point of care and lab-based)• Perform operational research to define best adapted and most feasible
tests for different settings• Introduce viral load testing in a phased in approach
– Define testing frequency– Replace CD4 monitoring with viral load monitoring– Implement evidence-based algorithms to prioritise patients
Laboratory-based test Point-of-care test
Sample Plasma, DBS Fingerstick, heelstick
Sample volume
200 – 1000μl ≤100μl
Sample prep Simple, no contamination Simple, part of POC test
Consumables Minimal, open access Minimal (1 lancet, 1 collection tube, 1 cartridge)
Reagents No cold storage, stable ≥40°C for ≥18 months
Part of cartridge, no cold storage, stable ≥40°C for ≥18 months
Power AC and battery AC, battery (≥8 hours), solar
Instrument Open access and polyvalent, 1 room, no contamination
Closed system, automated, small and lightweight, environmentally robust (heat, humidity, rigorous movement)
Hands-on time ≤1 hour ≤10 minutes
Time to result ≤1 day ≤30 minutes
Range Quantitative, all subtypes, ≥50 copies/ml
Quantitative / semi-quantitative, all subtypes, ≥1000 copies/ml
Training / skill Medium Minimal, basic (≤2 days), no precision pipetting
Regulation WHO PQ (opt CE, FDA) WHO PQ (opt CE, FDA)
Cost per test ≤$10 ≤$8
Instrument ≤$5000 (all required) ≤$1000 (single instrument)
Simplifying sample transport by using DBS• Quick processing of whole blood• Inefficient sample networks• Alternative: dried blood spots• Long distances, ambient
temperature• Time to result: e-health, m-health• Fingerprick DBS• NucliSENS EasyQ® HIV-1 v2.0 viral
load test (bioMerieux) for DBS• MSF validation of fingerprick DBS
in Malawi• Other tests for use with DBS?
NucliSENS EasyQ® HIV-1 v2.0 (bioMérieux)• Thyolo district hospital, Malawi• DBS validated• Real time NASBA (isothermal signal
amplification), RNA specific• Logistical challenges:
– laboratory infrastructure – unreliable power supply– unreliable water supply – provision of RNAse-free water– unreliable air-conditioning– non-adherence to cold chain transportation,
especially at customs– inability to find local laboratory technicians
with molecular biology expertise– lack of in-country trouble-shooting and
maintenance services
1. Extraction room
2. Amplification room
Generic HIV viral load assay (Biocentric)
• Nhlangano health center, Swaziland
• Open system, low cost• Real time RT-PCR (DNA and
RNA)• Logistical challenges• Use of plasma as a
sample type (use of DBS is research use only)
• Most of the other challenges as for the NucliSENS test
ExaVirTM Load Version 3 (Cavidi)
• Yangon, Myanmar (field site is in Shan state)• Subtype independent, relatively low cost, minimal lab
requirements, not as prone to contamination and not as dependent on precision pipetting as molecular lab tests
• ELISA of HIV reverse transcriptase activity
Challenges include:•Must be performed on plasma•Plasma must be frozen at -20°C•Need for back-up vacuum pump•Relatively low through-put for lab test•Good water quality is essential•Positive and negative controls must be
supplied in-house•Sample preparation to isolate the reverse
transcriptase enzyme is labour-intensive
Formore information,
please grab a copy of our viral load report
(also available on our website:
www.msfaccess.org)
Performance evaluation of SAMBA semi-quantitative HIV viral load test
for therapy monitoring in resource-poor settings
Dr. Suna Balkan
MSF Aids Working Group
Inclusions/month Cumulated patients under ART
0
1000
2000
3000
4000
5000
6000
7000
2001 2002 2003 2004 2005
Scaling-up in the MSF project Chiradzulu district, Malawi
Decentralisation
Task shifting Need for a POC VL
SAMBA system characteristics
• All HIV1 subtypes & recombinants• Threshold 1,000 copies/ml• Heat stability at 50°C
• Robust & simple instrument
• No or minimum electricity• Minimum handling• No risk of contamination• Turn around time allowing same
day result• Affordable cost
• Can detect Groups M, N, O & recombinants
• Cut-off at 1,000 copies/ml• Heat stable reagents; no cold
chain transport or storage• Isothermal amplification with
simple visual detection • Low power requirement 350W• Preloaded reagents in a closed
cartridge• Test time = 90 minutes with
throughput of 24/day at 6.5 hr working day
MSF requirements SAMBA
Visual readout of SAMBA semi-quant VL test
<1,000 cp/ml ≥1,000 cp/ml
SAMBA system
SAMBA-prep(sample extraction)
SAMBA-amp(amplification)
1 to 4 samples per run
* Roche TaqMan accuracy: +/- 0.3 Log per package insert
Evaluation of SAMBA London St Thomas & Royal London Hospitals in 134 clinical samples
Concordance between SAMBA & Roche = 97.8 % (131/134)
< 500(<2.7 log)
500 – 2000(2.7- 3.3 log)*
>2,000 (>3.3 log) Total
SAMBA >1,000 2 2 34 38
SAMBA < 1,000 93 2 1 96
Total (%) 95 (71%) 4 (3%) 35 (26%) 134
Roche Taqman v2 (copies/ml)
• Malawi– 13.2 million population mainly rural – 1 million HIV-infected
• MSF project based in a rural district– 1 hospital (laboratory),10 health centres– HIV care in 2000,decentralisation in 2003– 25 000 patients followed under ART – 80% followed in the 10 decentralised health centres– Integrated project with MOH
MSF Chiradzulu project background
MSF Arua project background
• Northwestern Uganda• Arua + catchment population : 1,5 M• HIV prevalence 3%• ART project since 2002• Arua District Hospital• 7000 patients followed under ART • Integrated project with the MOH
SAMBA tested on-site by MSF technician
SAMBA tested on-site by MSF technician
Roche TaqMan v2 at Royal London
Hospital
Roche TaqMan v2 at Royal London
Hospital
Abbott RealTime PCR at Addenbrooke
Abbott RealTime PCR at Addenbrooke
SAMBA field trials in Malawi and Uganda
200 HIV+ patients in Malawi 154 HIV+ patients in Uganda recruited
from HIV clinic during routine visit
200 HIV+ patients in Malawi 154 HIV+ patients in Uganda recruited
from HIV clinic during routine visit
200 µl fresh plasma Frozen plasma shipped directly
Results to MSF Results to MSF
Discordant SAMBA/Roche
All testing blinded to each other
Malawi results – SAMBA vs Roche TaqMan v2
Viral Load (cp/ml)< 500
(<2.7 log)500 – 2,000
(2.7- 3.3 log)*>2,000
(>3.3 log) Total
SAMBA >1,000 4 4 46 54
SAMBA < 1,000 142 4 0 146
Total (%) 146 (73%) 8 (4%) 46 (23%) 200
Overall concordance with Roche v2 = 98% (196/200)
Roche TaqMan version 2
* Roche TaqMan accuracy is +/- 0.3 Log per package insert
Uganda results – SAMBA vs Roche TaqMan v2
Viral Load (cp/ml)< 500
(<1.7 Log)500 – 2,000*(2.7-3.3 Log)
>2,000 >(3.3 Log) Total
SAMBA >1,000 2 0* 56 58
SAMBA < 1,000 90 2* 4 96
Total (%) 92 (60%) 2 (1%) 60 (39%) 154
Overall concordance with Roche v2 = 96.1% (148/154)
Roche TaqMan v2
* Roche TaqMan is 0.3 Log accuracy (package insert)
Conclusion
• SAMBA platform is much simpler than currently available molecular technologies which require highly-trained personnel and sophisticated infrastructure only available in centralised laboratories
• SAMBA device is much easier to handle and being a closed system, prevents contamination by amplicons
• Staff training requirement for SAMBA is minimal
• SAMBA can be implemented in lower healthcare levels such as district hospitals or health centres with a basic laboratory but supplied with electricity
• Routine use of Samba will be now implemented in Arua and Chiradzulu with on going evaluation
• Will improve HIV care in a decentralization & task shifting strategy
Virological efficacy of ART over time at MSF sites in Arua and Chiradzulu
<0.5 0.5-1 1-2 2-3 3-4 4-5 5-6 >60%
20%
40%
60%
80%
100%
<40
<1000
Years on ART
% o
f p
ati
en
ts
> 65 % of patients on ART have VL < 40 cp/ml after 6 months> 80 % of patients on ART have VL < 1,000 cp/ml after 6 months
n = 284
Distribution of viral loads in treated and untreated individuals in Malawi & Uganda
0%
10%
20%
30%
40%
50%
Roche TaqMan v2 viral load (cp/mL)
% o
f p
ati
en
ts
> 1x106
1,000 cp/ml
1x105 1x104 1x103 1x102 <100 <40
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