Background on HIV in South Africa
South Africa is an upper–middle-income country with the second-largest economy in
Africa.
1
In mid 2015, the population was estimated at 54.96 million; 51.0% were women and 30.2%
were younger than 15 years of age.
2
The population density, age and gender structures, however, vary significantly.
South Africans have a high burden of communicable diseases such as HIV and tuberculosis,
as well as non-communicable chronic diseases such as diabetes, hypertension and cancer.
3
Life expectancy has seen progressive increases over the years, in part due to the
rapid and effective scale-up of HIV and tuberculosis care in the country.
2,4
In 2015, life expectancy was 60.6 years for men and 64.3 years for women.
2
However, maternal and child mortality rates are relatively high compared to other
middle-income countries.
4,5
The latest UNAIDS estimates for 2015 indicated that almost 7 million [6.7–7.4 million]
South Africans were living with HIV.
6
In the 15–49-year age group, prevalence was as high as 19.2%, with women the worst
affected.
6
In the 0–14-year age group, 240 000 children are estimated to be living with HIV.
6
Antiretroviral therapy coverage is expanding, with approximately 3.4 million South
Africans currently receiving antiretroviral therapy and close to 4 million predicted
to be on antiretroviral therapy in the 2016 and 2017 fiscal year.
3
Current laboratory infrastructure and HIV-related testing in South Africa
Healthcare in South Africa is two-tiered, consisting of a public sector serving over
80% of the population and a smaller private sector catering to the middle- and upper-income
population, largely through medical insurance. The South African National Department
of Health (NDoH) has overall responsibility for healthcare, but is particularly responsible
for the public sector. South Africa is divided into nine provincial Departments of
Health; each is responsible for managing and providing comprehensive healthcare services
through a district-based model.
1
An approximate 4420 primary public healthcare facilities are available, of which 3991
provide HIV treatment services.
1,7
Diagnostic testing in the public sector is the mandate of the National Health Laboratory
Service (NHLS), the largest pathology service provider in the country. The NHLS is
a national public entity established through the amalgamation of a number of public-sector
laboratory service providers and various Provincial Department of Health laboratories.
8
The NHLS serves more than 80% of the population through a network of over 260 laboratories
throughout the nine provinces.
The National Priority Program was established in 2010 to provide support to the NHLS
and NDoH through the management, coordination, standardisation and implementation
of a number of National Programmes, including HIV viral load, early infant diagnosis
(EID), tuberculosis, CD4 and, more recently, HIV drug resistance. The National Priority
Program now supports 16 regional laboratories for HIV viral load testing, nine laboratories
for EID, 52 regional laboratories for CD4 testing, 211 GeneXpert® MTB/RIF testing
sites and five HIV drug resistance testing laboratories (Figure 1).
FIGURE 1
GIS map of testing laboratories implemented by the National Priority Program throughout
South Africa. There are currently (a) 52 CD4 (yellow), (b) 16 viral load (red) and
(c) 211 GeneXpert MTB/RIF (green) testing laboratories.
Further infrastructure supporting the NHLS programme includes significant investment
into the NHLS laboratory information system using TrakCare or DisaLab, to which all
analysers within the NHLS are interfaced. All national test results are collected
centrally and archived within a single central data warehouse, which is a large server
able to store, manage and analyse all laboratory information system data from all
tests generated.
For CD4 testing, the routine method employed is PanLeucogating, a cost-effective technology
developed within South Africa and licensed to Beckman Coulter.
9,10
Approximately 3.6 million PanLeucogating CD4 tests were performed within the NHLS
in 2015.
South Africa has also evaluated the Alere Pima™ CD4 technology and other point-of-care
(POC) devices.
11,12,13
A number of Pimas have been implemented by non-government organisations
14
and Department of Health facilities in certain provinces for pilot studies, but the
South African NHLS has not yet adopted Pima or any other POC technology for wide-spread
implementation. This has mainly been due to current reliable CD4 services with good
laboratory turnaround times
7
and the prohibitive cost of implementing widespread CD4 testing at the POC.
15
However, with increasing testing demands, expansion of CD4 testing services is required.
A newly-proposed CD4 testing model, the Integrated Tiered Service Delivery Model
7
(Figure 2), provides a service delivery system that enables high-volume testing on
one end, whilst integrating and extending laboratory services into small laboratories
with existing infrastructure, to rapidly scale up services, to lower volume sites
on the other end. Placement of testing equipment is therefore, in accordance with
service needs; in a community laboratory, for example, small automated equipment is
placed to test 100–150 samples per day, covering the service needs of all the local
clinics in the area,
7
whereas in very remote sites, without any reasonable access to a laboratory and where
less than 30 tests per day are needed, multiple POC technologies can be used to supplement
and extend laboratory services, facilitating total service coverage
7
(Figure 2).
FIGURE 2
Integrated Tiered Service Delivery Model. The proposed NHLS CD4 tiered laboratory
network structure comprises six service tiers, which support decreasing service test
volumes in increasingly remote sites. Tier 1 (servicing a single site) and Tier 2/‘POC
Hub’ (servicing up to 10 remote clinics) utilise multiple POC technologies to extend
laboratory services (HIV, tuberculosis) in remote, hard-to-reach areas, beyond a reasonable
distance to a Tier-3 laboratory; Tier 3 represents a community laboratory that serves
> 10 < 50 clinic sites; Tier 4 and Tier 5 are regional laboratories or ‘metro’ centralised
laboratories performing high-volume testing; Tier 6 represents coordinated, harmonising
national support from an expert team or reference laboratory.
7
The Integrated Tiered Service Delivery Model is currently being implemented in the
NHLS
7
and has demonstrated success
16
in substantially reducing turnaround times of reporting in remote areas of South Africa,
thus ensuring total service coverage and rapid turnaround times, irrespective of where
services are provided
7
(Figure 2). Costs of the Integrated Tiered Service Delivery Model are contained and
remain fixed across a network, whilst still providing reasonable access to service.
Although the decentralised approach using POC (at the Tier 1 or Tier 2 level) has
been shown to cost five to seven times more than a conventional laboratory-based service,
15
these higher costs can be cross-subsidised by the majority of national service requirements
(in South Africa > 90%) being met by significantly more cost-efficient conventional
laboratories
7,15
at Tiers 3, 4 and 5.
7
The Integrated Tiered Service Delivery Model approach further enables a network for
technical and quality support for lower tier sites, with lower tier sites supported
within a defined locality by the nearest higher tier sites.
HIV viral load testing within the NHLS relies on centralised, high throughput, laboratory-based
testing. The tender is awarded every three years through a highly competitive selection
process and for the last two rounds has used two suppliers, namely Abbott Molecular
and Roche Molecular Diagnostics. Within the 16 HIV viral load laboratories nationwide,
13 laboratories utilise either the Roche COBAS® Ampliprep/COBAS® TaqMan® version 2
or the high throughput cobas® 8800/6800 systems and three use the Abbott m2000 Realtime™
HIV-1 system. All instruments are fully automated, interfaced, real-time platforms
which facilitate a faster result turnaround time. In 2015 alone, over 3.5 million
viral load tests were performed and this number is anticipated to increase to almost
5 million if testing targets are met for the next fiscal year (April 2016–March 2017).
In addition to scaling up centralised testing, the NHLS is also considering adopting
a tiered viral load testing model using a combined approach of high throughput, mid-throughput
and POC platforms and is embarking on a pilot project to evaluate the feasibility
of such a model in collaboration with the NDoH.
EID is performed in nine laboratories on the Roche COBAS Ampliprep/COBAS TaqMan platform
using the qualitative COBAS Ampliprep/COBAS TaqMan HIV-1 Test, v2. During 2015, approximately
450 000 HIV PCR tests for EID were performed. Due to changes in the clinical algorithm,
which includes birth testing and follow-up testing to avert early mortality prior
to three months of age, these numbers should theoretically increase significantly
and POC technologies may have a place for niche testing, but will require further
investigation.
The South African NDoH estimates that 60% – 70% of all HIV-positive persons are also
co-infected with tuberculosis.
3
Thus, together with the NHLS, the Department of Health have been global leaders in
rolling out GeneXpert® MTB/RIF testing in South Africa. A total of 314 GeneXpert instruments
of varying sizes have been placed in 211 sites, in both urban and rural settings,
with expansion of the programme to special risk populations such as correctional facilities
and peri-mining communities. In future, GeneXpert® MTB/RIF testing laboratories may
be used for decentralisation and expansion of viral load testing services.
Current quality assurance framework and policy for HIV testing in South Africa
The NHLS has implemented a Quality Management System in compliance with various standards
(ISO 15189, ISO 17025, ISO 9001 and ISO 17043) and the competence of all medical testing
laboratories is, therefore, in accordance with the relevant ISO standard and guidelines
for Good Laboratory Practice. Clinical Pathology laboratories operate according to
the requirements of ISO15189:2012.
The NHLS National Quality Assurance Division is the national quality-related policy-setting
body and is responsible for establishing, documenting, implementing, maintaining and
continually improving the quality management system. The National Quality Assurance
Division manages the in-house production and distribution of External Quality Assessment
(EQA) material. These proficiency testing schemes are offered both internally and
externally, to private laboratories in the country and also to 23 countries outside
of South Africa, in several pathology disciplines, and are operated in accordance
with ISO/IEC 17043:2010. The National Quality Assurance Division is also responsible
for ensuring that NHLS laboratories are accredited by the South African National Accreditation
System through implementation of standard requirements, including participation in
EQA programmes/proficiency testing and auditing against ISO 15189 for medical testing
laboratories.
CD4 laboratories participate in the NHLS EQA programme and Beckman Coulter 3-IQAP
and also monitor internal quality measures (flow count rates) to ensure ongoing excellence
of service.
All viral load testing laboratories participate in the Quality Control for Molecular
Diagnostics EQA programme and Centers for Disease Control Dry Test Tube programme;
both programmes are coordinated by the NHLS Quality Assurance Division. EID testing
laboratories participate in the NHLS Dried Blood Spot EQA Program.
Specifically for the CD4, HIV and tuberculosis programmes, the National Priority Program
provides monitoring through:
Monthly meetings with suppliers to identify problem areas, monitor monthly turnaround
times, stock control, instrument breakdowns and throughput.
Site monitoring, including monthly indicator reports detailing test volumes, errors
and training needs and which are reviewed and actioned accordingly.
For HIV viral load, a process of continuous quality monitoring is used through remote
connectivity:
◦
The use of the Abbott mView software for all HIV viral load laboratories utilising
the Abbott platform.
◦
The use of remote connectivity software (Axeda) for all HIV viral load laboratories
utilising the Roche platform.
◦
The use of an antiretroviral therapy dashboard for continuous monitoring of laboratory
performance. This dashboard was developed together with the NHLS Central Data Warehouse
and generates monthly reports for both internal and external stakeholders in terms
of test volumes and result ranges from national and provincial down, to district level
for HIV viral load, CD4 and EID.
Laboratory site visits and assistance for accreditation.
National quality assurance programme for point-of-care testing in South Africa
A final policy draft is being vetted for quality assurance of POC testing and the
NHLS will play a pivotal role in the management and support of POC testing services
to ensure it performs to the same quality standards as current diagnostic testing.
The NHLS should take full responsibility for implementation of technology, training,
monitoring and evaluation, procurement and stock control.
7
POC testing sites will implicitly follow ISO 22780 and NHLS will manage relevant accreditation
procedures for sites performing POC testing.
17
A key component of the quality assurance programme will be the inclusion of internal
and external quality control procedures and management. The provision of quality assurance
schemes for POC testing will be the responsibility of the NHLS, which already has
the capacity, expertise and proven experience to establish and implement new programmes.
As an example, the NHLS assisted the NDoH in ensuring the quality of the approximate
8 million rapid HIV tests performed per year, through development of materials, test
kit monitoring and training. This included development of a quality assurance plan
and quality improvement programme in collaboration with the Centers for Disease Control,
which has been adopted by the NDoH. As part of these activities, post-market surveillance
of rapid-test kit lots is conducted prior to national release. The quality assurance
programme for rapid HIV testing is still an area in need of improvement. Some of the
key challenges experienced during implementation of the rapid HIV testing quality
assurance programme included: staff not implementing what was taught during training;
lack of understanding of quality management principles; staff not adhering to quality
assurance testing procedures due to high workload; and lack of knowledge transfer
following training.
Many of these challenges have been overcome using the following strategies:
Initiation of ‘Train-the-trainer’ workshops.
Development of a draft quality plan which is made available to sites.
Training of Provincial coordinators who have overall site management and can follow
up on problem sites.
Introducing more follow-up site visits to check compliance.
The GeneXpert® MTB/RIF Dried Culture Spot EQA programme, developed in collaboration
with University of the Witwatersrand in 2011,
18,19
is another example of NHLS expertise. The Dried Culture Spot EQA has become an integral
component to the GeneXpert® MTB/RIF programme and now supports ~391 sites in 24 countries.
The material is manufactured and distributed in-house and is easy, safe, stable and
cost effective. The programme is supported by an automated, real-time reporting and
quality monitoring web-based tool, TBGx Monitor™ (www.tbgxmonitor.com), which remotely
collects and analyses EQA data by uploading the data from individual GeneXpert modules.
This programme has also shown success in non-laboratory users
18
and is being expanded to other molecular tuberculosis diagnostic platforms
20
as well as adaptation to other diseases. A similar quality assurance model will likely
be developed for POC technologies.
Conclusion
If POC testing is expected to improve and support diagnostic and clinical services
in South Africa, the laboratory needs to play a major role in ensuring success of
the programme through a POC quality assurance framework, much the same as for laboratory
testing. The NHLS has demonstrated proven success in conceptualisation and implementation
of quality management systems for national programmes and will adopt a similar strategy
for POC testing through the Integrated Tiered Service Delivery Model.