However we are left with the problem that there is currently no viral load test that is practicable for use out in the field in a resource-poor setting far from laboratory facilities. Current tests require taking a vial of blood from a vein, refrigerated transport to a laboratory, mains electricity to run equipment, an assortment of scientific paraphernalia, instruments that cost in the region of $30,000-$60,000, about eight hours to produce a result and a technician with advanced training in molecular biology lab techniques.
In early 2006 MSF organised a consultation among academics and workers in ARV rollout programmes to find a specification for an ideal viral load test for resource-poor settings. They decided that it should require no more than a fingerstick’s worth of blood (about a tenth of a millilitre), a single cartridge into which a sample of blood could be inserted and which would give a result, that it should not require refrigeration, be able to be run on batteries, should not cost more than $1000 per instrument and $8 per test, should give a result within two hours and would be able to be done by a field health worker with 1-2 days’ training.
Such a test does not yet exist, though price reductions have been negotiated for the current systems, and reagents that do not require refrigeration have been developed. Costs can be greatly cut by making the test one which will give a simple either/or result to the question of whether the viral load is above a certain level, rather than measuring a continous variable between 50 copies and 1 million copies.
What this level should be is likely to be a matter for debate. Calmy and colleagues point out that evidence from the PLATO Collaboration, an international merging of 13 HIV cohort studies which contributes 2,488 patients experiencing triple-class virologic failure, suggests that, as long as the viral load remains below 10,000 copies, CD4 counts remain stable and the risk of clinical progression is low. So do other cohort studies (see Schechter). “Clearly a qualitative test with a cutoff value of 10,000 copies/mL would be of immediate practical use,” they say.
However avoiding AIDS is one thing and avoiding drug resistance and the failure of any subsequent regimen is another, and evidence both from Khayelitsha and from an older analysis of the same PLATO Collaboration (see Ledergerber) shows that if patients are allowed to maintain a viral load over 1,000 for more than four months, only a minority are able to re-suppress HIV on a new regimen.
Researchers at Cambridge University in the UK (see Dineva) are developing a prototype ‘dipstick’ that would indicate the presence of a significant viral load (over 500 is the lower limit) by the intensity of a single test line. The difference between 1,000 and 10,000 copies may not be all that crucial if the illustration of the dipstick results accompanying Calmy’s article are what it will eventually look like: whereas viral loads under 500 produce a faint line and over 10,000 a strong one, viral loads in between produce a line whose fuzziness is a matter of interpretation, so perhaps the indication should be that “any line that isn’t faint means you switch”. Dineva and colleagues say that the dipstick test can produce a viral load result “with an efficiency similar to that of a complex, expensive, and instrument-dependent method.”
What of the WHO and its public health approach? The organisation is wary of any tendency to “make the best be the enemy of the good” and would continue to oppose any demand that ARV programmes not be instituted where viral load testing is unavailable. But the organisation has shifted its position on other guidelines. At Glasgow Gilks said that single-dose nevirapine to prevent mother-to-baby transmission, another strategy supported by WHO in the past, “is now substandard”, and the WHO has started to shift its position on d4T, saying that “some governments may want to choose alternative options” due to this drug’s side effects.
However some are wishing that the WHO would move faster and would explicitly echo the same sense of urgency, before health systems in the developing world are swamped by tens of thousands of patients with NNRTI and thymidine-analogue resistance mutations. In an editorial in the same issue of Clinical Infectious Diseases Robert T Schooley of the Univeristy of California, San Diego compares the current situation to the old joke where a man jumps off a 10-floor building and is asked by someone in the fifth floor how he is as he falls past. “Doing fine so far,” is the reply. “We must avoid invoking the ‘fifth-floor syndrome’ by failing to act to prevent what we know will happen if viral load testing is not expanded in concert with the access to antiretroviral drugs,” is Schooley’s comment.