Progress report of AffordCD4.com – the first two years

Dear  colleagues,  

Firstly, following our priming efforts (1,2,7,9) and the publications of review papers that emphasized the large variations in the costs of CD4 tests (5-7), the scientific community responded with enthusiasm and introduced flow cytometric protocols, including the PanLeucogating (7,9), that are more robust and reliable. At the same time, these assays are far more affordable then those recommended by the previous international guidelines. On the 15^th April 2002 the special issue of Clinical Cytometry 50: (2) 2002, edited by Frank Mandy and dedicated to CD4 enumeration, was published including various novel aspects of this diagnostic technology (see pages 77-78 in AIDS Full_papers.pdf  - and papers  8-10).

 Secondly, the news of a price reduction in CD4 testing has reached the relevant appreciative audience and elicited a fanfare reception from the South African press and the Witwatersrand University in Johannesburg. They all paid a special thank-you to Debbie Glencross for her pioneering contribution to this field (see folder “Accolade in SouthAfrica”). All this happened on the same week (14-22^nd April 2002) when President Mbeki of South Africa has, at long last, shifted his views about the role of HIV infection and the need for therapy in AIDS.  What a week this was!

 Thirdly, in response to the generic drug concept, we have introduced the concept of generic monoclonal antibodies. These currently include, in line with the PanLeucogating Protocol (4,7,9), the CD4, CD8 and CD45 reagents (2-4) that are now distributed to a number of centres. As a result, the PanLeucogating protocol has already been introduced, with success, to other African laboratories (see Acknowledgement and our Website). These issues will be covered in great detail on our website.

 Finally, Howard Shapiro on the AffordCD4 website has invited the flow-cytometry industry to design simpler and more versatile small clinical cytometers. Indeed, the potential of these instruments is now proven (10), and we also emphasize that the same type of equipment is also optimal for performing the flow based multiplexed assays for the differential diagnosis of infectious diseases (11).

The instrumentation, however, still remains a vexed issue, to be solved during the second phase of AffordCD4 programme. Industry may need to move faster now that the first set of results are in evidence.  The schemes for evaluating these new instruments are in place (3,10). It is now documented that the new protocols using generic antibodies are optimally run on volumetric single-platform instruments (4) – but only few of these cytometers are currently in operation, and some others have as yet not been fully tested in multicentre trials for their performance. So, only with new industrial investments will it be possible to expand these brilliant technologies to cover the increasing workload associated with CD4 enumeration as well as with the exciting practical areas of HIV service work that are also already in the pipeline (11-14).      

Congratulations to Debbie !

On 5^th May 2002

from 

George Janossy and Ilesh Jani 

HIV Immunology

Royal Free and University College Medical School     London NW3 2QG U

References 

1. Sherman GG, Galpin JS, Patel JM, Mendelow BV, Glencross DK. CD4+ T cell enumeration in HIV infection with limited resources. J Immunol Methods 1999; 222(1-2): 209-17.

 2.  Janossy G, Jani I, Gohde W. Affordable CD4(+) T-cell counts on 'single-platform' flow cytometers I. Primary CD4 gating. Br J Haematol 2000; 111(4):1198-208.

 3.  Jani IV, Janossy G, Iqbal A, Mhalu FS, Lyamuya EF, Biberfeld G, et al. Affordable CD4+ T cell counts by flow cytometry. II. The use of fixed whole blood in resource-poor settings. J Immunol Methods 2001; 257(1-2): 145-54.

 4.  Janossy G, Jani IV, Bradley NJ, Bikoue A, Pitfield T, Glencross DK. Affordable CD4+ T cell counts by flow cytometry III. CD45 gating for volumetric analysis. Clin Diag Lab Immunol 2002;In press.

 5.  Brando B, Barnett D, Janossy G, Mandy F, Autran B, Rothe G, et al. Cytofluorometric methods for assessing absolute numbers of cell subsets in blood. European Working Group on Clinical Cell Analysis. Cytometry 2000; 42(6): 327-46.

 6.  Brando B, Scarpati B, D'Avanzo G. Development of simplified, inexpensive flow cytometry for CD4+ T cell counting. www.Affordcd4.com 2001.

 7.  Glencross DK, Scott LE. CD4  Tcell monitoring for HIV/AIDS: old options; new insights. SADJ 2001; 56(12): 602-5.

 8.  Mandy F, Nicholson J, Autran B, Janossy G. T-cell subset counting and the fight against AIDS: reflections over a 20-year struggle. Cytometry (Clin. Cytometry) 2002; 50(2): 39-45.

 9.  Glencross DK, Scott LE, Jani IV, Barnett D, Janossy G. CD45-assisted PanLeucogating for accurate, cost-effective dual-platform CD4+ T-cell enumeration. Cytometry (Clin. Cytometry) 2002; 50(2): 69-77.

10. Janossy G, Jani IV, Kahan M, Barnett D, Mandy F, Shapiro H. Precise CD4 T-cell counting using red diode laser excitation: for richer, for poorer. Cytometry (Clin. Cytometry) 2002; 50(2): 78-85.

11. Jani IV, Janossy G, Brown DW, Mandy F. Multiplexed immunoassays by flow cytometry for diagnosis and surveillance of infectious diseases in resource-poor settings. Lancet Infect Dis 2002;2(4):243-50.

12. Bikoue A, Janossy G, Barnett D. Stabilised cellular immunofluorescence assay (SCIFA): CD45 expression as a calibration standard for human leucocytes. J Immunol Methods 2002;In press.

13. Tilling R, Kinloch S, Goh LE, Cooper D, Perrin L, Lampe F, et al. Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection. Aids 2002; 16(4):589-96.

14. Goh LE, Perrin L, Hoen B, Cooper D, Phillips A, Janossy G, et al. Study protocol for the evaluation of the potential for durable viral suppression after quadruple HAART with/without HIV vaccination: the QUEST study. HIV Clin Trials  2001; 2(5): 438-44.  

These publications are compiled on an AffordCD4 CD. 

This CD is available, in a limited number to those who work in this field, when requested (e-mail: janossy@rfhsm.u-net.com)

Acknowledgements

We, David Barnett, Bruno Brando, Deborah K. Glencross, Ilesh Jani, George Janossy, Frank Mandy and Howard Shapiro, are grateful to many individuals for their help and encouragement. We are especially grateful to the following people for providing the AffordCD4 initiative their continued support:

Prof. Brigitte Autran, Hopital Pitie Salpetriere, Paris, France

Dr. Barbara Bannister, Royal Free Hospital, London, UK

Dr. Jorge Barreto, Instituto Nacional de Saúde, Maputo, Mozambique

Dr. Simon Barry, Royal Free Hospital, London, UK

Prof. Umberto Bertazzoni, European Commission, Brussels, Belgium

Prof. Peter Beverley, Edward Jenner Vaccine Institute, Compton, UK

Prof. Gunnel Biberfeld, Karolinska Institute, Solna, Sweden

Dr. Arsene Bikoue, University College London, London, UK

Dr. Nicholas Bradley, University College London, London, UK

Dr. Dorothy Bray, Glaxo SmithKline, London, UK

Dr. Benjamin Cheng, ProjectInform, New York, USA

Dr. Hazel Dockrell, London School of Hygiene and Tropical Medicine, London, UK

Dr. Robert Downing, CDC/UVRI Research Collaboration, Entebbe, Uganda

Dr. Jean Emmanuel, World Health Organization, Geneva, Switzerland

Mr. Keith Fell, University College London, UK

Mr. Cassim Gassiep, CEO National Health Laboratory Services, South Africa

Dr. Diana Gibb, Medical Research Council, London, UK

Dr. Li-Ean Goh, Glaxo SmithKline, London, UK

Prof. Wolfgang Gohde, Institut fur Strahlenbiologie, Munster, Germany

Mr. Gregg Gonsalves, GMHC, New York, USA

Mr. Vivian Granger, UK NEQAS, Sheffield, UK

Dr. Jan Gratama, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands  

Prof. Glenda Gray,  Perinatal HIV Research Unit Chris Hani Baragwanath Hospital, Johannesburg

Dr. Ashraf Grimwood, Bristol Myers Squibb “Secure the Future” Foundation, South Africa

Dr. Harvey Holmes, NIBSC, Potters Bar, UK

Dr. Melvyn Kahan, University College London, London, UK

Dr. Annabel Kanabus, AVERT, Horsham, UK

Dr. Sabine Kinloch, Royal Free Hospital, London, UK

Prof. Joep Lange, Academical Medical Center, Amsterdam, The Netherlands

Prof. Roland Levinsky, University College London, London, UK

Prof. Eligius Lyamuya, Muhimbili University, Dar es Salaam, Tanzania

Prof. Peter Lydyard, University College London, London, UK

Dr. Henry Maseruka, Glaxo SmithKline, London, UK

Dr. Hugh McDade, Glaxo SmithKline, London, UK

Ms. Laura McGee, Medical Research Council, London, UK

Dr. Julian Meldrum, NAM, London, UK

Prof. James McIntyre, Head,  Perinatal HIV Research Unit Chris Hani Baragwanath Hospital, Johannesburg

 Prof. Barry Mendelow, University of Witwatersrand, Johannesburg, South Africa

Dr. Tom Mercolino, Ortho Diagnostics Systems, Raritan, USA

Prof. Fred Mhalu, Muhimbili University, Dar es Salaam, Tanzania

Dr. Peter Mugyenyi, Joint Clinical Research Center, Kampala, Uganda

Dr. Peter Mwaba, University of Zambia School of Medicine, Lusaka, Zambia

Dr. Volker Ost, Partec, Munster, Germany

Mr. Tim Pitfield, University College London, London, UK

Dr. Mark Rayfield, CDC, Atlanta, USA

Prof. John Reilly, UK NEQAS, Sheffield, UK

Dr. Gregor Rothe, Klinikum der Universitat Regensburg, Regensburg, Germany

Prof. Jorg Schupbach, University of Zurich, Zurich, Switzerland

Dr. Ian Sanne, University of Witwatersrand, Johannesburg, South Africa

Ms. Lesley Scott, University of Witwatersrand, Johannesburg, South Africa

Dr. Gayle Sherman, University of Witwatersrand, Johannesburg, South Africa

Dr. Geoffrey Shield, NIBSC, Potters Bar, UK

Dr. Wendy Stevens, University of Witwatersrand, Johannesburg, South Africa

Mr. Ian Storie, UK NEQAS, Sheffield, UK

Mr. Richard Tilling, University College London, London, UK

Dr. Sitefano Tugume, Joint Clinical Research Center, Kampala, Uganda

Dr. Gaby Vercauteren, World Health Organization, Geneva, Switzerland

Dr. Tobias R. de Wit, PharmAccess International, Amsterdam, The Netherlands

Mr. Liam Whitby, UK NEQAS, Sheffield, UK

Dr. Mike Youle, Royal Free Hospital, London, UK

Dr. Lynn Zijenah, University of Zimbabwe Medical School, Harare, Zimbabwe .

This CD is available, in a limited number to those who work in this field, when requested (e-mail: janossy@rfhsm.u-net.com).