The technology already exists to provide low-cost monitoring of antiretroviral treatment, according to Professor George Janossy of the Royal Free and University College School of Medicine. Prof Janossy, a Consultant Immunologist, was speaking at a NAM Seminar on Friday 17 November on the need for change in the methods used to monitor HIV treatment, to make it widely affordable as the cost of antiretroviral drugs is reduced.
Prof Janossy had attended two recent meetings on this subject, one on 8 November in Antwerp, organised by the European Group for Clinical Flow Cytometry, and a second on 11-13 November in Bethesda, Maryland, USA, organised by Gay Men's Health Crisis and Project Inform, supported by NIH and the Rockefeller Foundation. The conclusions of these meetings formed the core of his talk.
The increasing precision of the technology, routine availability of quality controls, and fixatives which allow samples to be transported for long distances without compromising test accuracy, have opened the way for high quality medical care to be provided for millions of people worldwide, he argued.
Current flow cytometers, used to measure CD4 counts, are over-complicated when used solely for this purpose. Companies also seek to tie in purchasers to using proprietary monoclonal antibodies, fixed on beads, which are inherently costly to produce. While beads have their uses, they are not needed for basic CD4 counts and may even reduce the accuracy of test results. Furthermore, the cost of commercial monoclonal antibodies has not fallen in line with the cost of manufacturing them.
Simplification can be achieved by providing CD4 counts and nothing else, using whole blood (treated with cheap chemicals to allow transport for 7-10 days to reference labs) and no more than two “generic” (copyright-free) monoclonal antibodies. These are now available for international use through the UK's National Institute for Biological Standards and Control - having been manufactured at a cost of just UKP 1,000 for 1 million doses.
Omitting beads from the test system, and coordinating the use of simplified flow cytometers with haematology analysers to obtain an absolute CD4 count, can not only cut the price of the tests but also - according to studies carried out by Dr Glencross at Witwatersrand University in South Africa - actually improve the accuracy of the results.
Ironically, some of the older flow cytometers now being discarded by western labs are more adaptable to cheaper and better systems than the latest models. In the short term, recycling used equipment could definitely help expand access to treatment in Africa and Asia, provided technicians can be trained to use it and provided appropriate results-focussed quality control schemes are put in place. In his own lab, Prof Janossy had tested this concept by training a technician, with no previous experience, to run 400 CD4 tests a day and document a high level of reliability in the results.
In one central African country, a multinational brewer which has committed itself to supporting medical treatment for employees with HIV has recruited an exile with qualifications in microbiology, who had been unemployed in Europe, to set up a laboratory to support its treatment access programme. There were many such opportunities that could be seized if others had similar imagination and flexibility. Private sector experience could be transferred to public health services in due course.
A further drastic reduction in the cost of CD4 tests could be secured by using exactly the same kind of red diode laser that is mass-produced for use in consumer CD players and other equipment, rather than expensive specialised medical lasers around which the main diagnostic companies have chosen to build their systems. Such simple instruments can be used with bead-based systems to run multiple diagnostic tests on a single blood sample. Howard Shapiro, a leading expert on flow cytometry, said in Bethesda that this would give the proposed device a wide range of medical uses, including improved and more rapid tests for HIV and other infections.
Unfortunately, the companies which currently dominate the market in medical diagnostics have no interest in introducing cheaper, simpler and more versatile systems.
It is likely, therefore, that the initial push to develop new systems will have to come from the public sector and foundations, possibly working with companies that don’t currently have an interest in medical diagnostics at all.
Prof Jorg Schupbach has argued that viral load tests may be replaced with much cheaper and simpler ELISA tests geared to detect the HIV core protein p24 in blood samples, provided that the samples are heated to disrupt any anti-p24 antibodies in the sample.
These tests have a substantial theoretical advantage over PCR-based tests where non-subtype-B variants of HIV-1 are concerned - in other words, the viruses that infect most people with HIV in Africa and Asia. This is because PCR tests depend on an almost exact match with part of the virus genetic sequence. In populations where this varies widely, or diverges from the ones on which the tests are based, the test becomes unreliable.
One implication is that sponsors of clinical trials, in the private and public sector, need to think about entry criteria and monitoring requirements for those trials. By requiring viral load monitoring and pre-set viral load levels as measured by over-specific tests, they could exclude people who ought to be included. On the other hand, if they required the running of new-generation p24 tests alongside viral load testing, they could help validate the technology and open up clinical research participation as well as access to low-cost high-quality clinical monitoring.
Happily, UNAIDS and the Rockefeller Foundation are already among those taking an interest in this area. However, the more that people working in the field ask questions and challenge the way tests are done, the higher the likelihood that access to them will increase in line with access to treatment.
Professor George Janossy is one of the key contributors to an Affordable CD4 website, which provides detailed technical information in support of this case.