Prices of CD4 assays and viral load tests must be reduced for developing countries
BMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7316.809b (Published 06 October 2001) Cite this as: BMJ 2001;323:809
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I understand that the West Indies is experiencing an epidemic of HIV
infection and the provision of sophisticated techniques for measuring HIV
viral load and anti-retroviral resistance may be of some benefit. For
developing countries in other parts of the World there isn't the
availability of laboratory facilities to support the analysers/techniques
associated with these tests. One viral load measurement is of limited
benefit as the value of the technique is in monitoring change over time.
Equally, resistance may change over time in relation to the
chemotherapeutic regimens used. Adequate support needs to be given to
patients to promote compliance with their treatment. Finally, once on
chemotherapy, currently, the expectation is for treatment lasting years.
It is obvious that for resource poor countries, even at heavily discounted
prices, the financial commitment would be relatively huge. With a limited
budget do you commit to saving many children's lives through appropriate
vaccination programmes where the treatment costs a few pence (eg. measles,
diphtheria, meningitis, tetanus), is highly beneficial, and has tangible
public health benefits or do you deny children this benefit by pursuing
more expensive activities?
Competing interests: No competing interests
Courtenay Bartholomew is correct when he calls for better
accessability to testing of VL and CD4 in resource poor settings. There
have been several advances in this direction recently, including the
ability to seperate CD4 and CD8 cells in novel and inexpesive assays.
In the context of effective vertical transmission interuption and
pediatric follow up, we have found that lack of CD4 and VL testing in the
field had very little impact when HAART therapy was not routinely
available, such as in Russia and the Ukraine, outside of the urban
centers. When using single dose prophylaxis to the mother at time of
delivery, simple ELISA testing with confirmatory test in antenatal period
or a single rapid test in the maternity house for women not booking as HIV
positive prior to delivery could be considered the acceptable "bare
minimum" for effective programs. In pediatric follow up, all infants
would be considered positive until proven otherwise and, until that time,
identifying the rapid progressors can be attempted without the use of CD4
or VL.
I agree with the author but hope that lack of CD4 and VL testing
wouldn't stand in the way of effective vertical transmission programs in
resource poor settings.
Competing interests: No competing interests
Affordable options for CD4 testing are possible.
To the Editor: The call for affordable methods of CD4 and VL testing for the monitoring of HIV/AIDS is indeed a worthy one (1, 2). However, whilst cheaper pricing of reagents from manufacturing companies would be gratefully received to relieve the burden of HIV/AIDS diagnosis and management, innovative solutions may be more sustainable. The old cliché "necessity is the mother of invention" is as true as it ever was. The South African biomedical community has a history of innovation (3) and more specifically, alternative affordable options for CD4 testing have been proposed (4). By simplifying typical existing Flow Cytometric CD4 T cell analysis (4), the cost of a CD4 assay can be reduced by as much as 90% of the cost of testing that is based on various North American or European guidelines (CDC, NCCLS, UK NEQAS, amongst others (5-7). The cost effective solution, termed "PanLeucogated" (PLG) CD4 T cell enumeration (4), relies on the use of a well quality controlled parameter: White cell count (WCC) instead of an Absolute Lymphocyte Count (ALC) that is typically used to generate a CD4 result (see website
http://www.affordCD4.com/affCD4_4.htm).
Coincidentally, this simple paradigm shift in defining the common denominator used for CD4 testing and the way in which the CD4 analysis is performed (total white cell versus lymphocyte gating), has implications beyond merely reducing the costs of CD4 testing (4). An important issue of reproducibility and quality control of CD4 reporting is addressed as well. Variation of ALC between different types of haematology analyser and between different laboratories is well documented (8-11). Typically CD4 counting, at least on the dual platform methodology, relies on the accuracy of the ALC. It is therefore not surprising that CD4 counts show relatively wide variation between laboratories when CD4 testing is solely based on the largely variable absolute lymphocyte count (thus the need for detailed guidelines that incorporate use of extensive panels of antibodies to ensure accuracy of CD4 results).
Testing based on current guidelines is however expensive (1, 2) and many laboratories have therefore opted for the lesser CD3/ 4 /8 combination conceivably in the interests of cost saving, especially in South Africa. Such "abbreviated" testing further widens inter-laboratory variation of CD4 reporting as guidelines are loosely adhered to. Single Platform flow cytometry options that incorporate use of "beads" as a counting standard or utilise volumetric testing, avoid the use of the ALC, and are more reproducible and accurate. Small instruments that perform dedicated CD4 counting (FACSCount (BD Biosciences, US) have also been shown to have good inter-laboratory reproducibility (12). Single platform technologies have therefore been recommended as the preferred method for generating an accurate, reproducible CD4 result (13, 14). "Bead" based counting is however technically more intensive and relatively expensive (15) and Flow Cytometric volumetric CD4 counting is obsolete, leaving Double Platform CD4 testing still as the most popular form of testing, despite relatively wide inter-laboratory variation.
We have therefore proposed the use of PLG CD4 testing as a cost effective yet accurate and reproducible alternative without loss of quality, which compares well to the accepted Single Platform "Bead" and Volumetric counting alternatives (4, 14). Although poor resources may have been the impetus to find a cheaper alternative, the idea that less (cost, effort and reagent) turned out to be more was an added bonus. Short-term fixatives (16,17) that assist with delayed laboratory testing may play a further important adjunctive role in facilitating truly robust, cheap CD4 T cell enumeration e.g. in Africa where resources are limited and specimens often need to travel long distances to centralised laboratories for testing.
Finally, let us also hope when the shoe is on the other foot, that as a third world country with a new patent* for CD4 T cell analysis, that we have the conviction to demand of ourselves the generosity we impose on the first world.
Glencross DK1 and Janossy G2.
1 Department of Molecular Medicine and Hematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,
2 HIV Immunology, Department of Immunology and Molecular Pathology, Royal Free and University College Medical School, London, NW3, United Kingdom.
* PATENT: PanLeucogated Absolute CD4+ T cell enumeration using white blood cells (defined by means of antibody, nuclear dyes or other means) as the basis from which to perform an absolute CD4+ T cell count, is registered under a provisional patent (Application No: 20015700) at the Registrar of Patents, Designs, Trade Marks and Copyright, Republic of South Africa and is covered internationally in terms of the Paris Convention.
References:
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Competing interests: No competing interests