Sara Gorman from Columbia University discusses viral load testing in resource-poor settings
In July of 2013, the World Health Organization (WHO) released new guidelines on antiretroviral therapy. Among the most significant new recommendations include: initiating ART earlier, in all individuals with a CD4 count of 500 per mm3 or less; starting ART at any CD4 count in particular populations, including pregnant and breastfeeding women and children under 5 years of age; and the use of viral load testing as the preferred method of monitoring response to ART and detecting treatment failure. Viral load measurement is already the method of choice for detecting treatment failure in high-income countries. But the recommendation has never included reliance on viral load measurement because middle- and low-income countries do not have the same access to the tools needed to measure viral load that high-income countries do. This raises an important question: are the new WHO recommendations realistic for low-income countries? If not, what needs to be done to achieve better access to technologies for viral load monitoring in resource-poor settings?
Viral load monitoring is often of critical importance to managing patients with HIV who take antiretrovirals. Viral replication in a patient taking ART can give rise to drug-resistant mutations as well as treatment failure. In addition, alternative drugs must be available in cases of treatment failure. If they are not, viral load testing to determine treatment failure is not useful.
Tim Hallett, Professor of Global Health at Imperial College London, says developing countries’ capacity for regular viral load testing is “variable.” According to Hallett, some places, such as central clinics and many places in South Africa, are able to include regular viral load testing in their treatment protocols, but provision of such care is currently much more difficult in more remote clinics. When it comes to routine viral load testing in developing countries, Helen Bygrave, a UK-trained general practitioner who works with Médecins Sans Frontières (MSF), disagrees. “We are starting to see it happen,” she says. “Overcoming the key barriers around sample transport and cost are what’s necessary and then ensuring funding follows the ideas and new technologies,” Bygrave comments.
Both viral load testing and the provision of second-line ART drugs in cases of treatment failure present significant challenges in low-income countries. Second-line drugs are currently much more expensive than first-line drugs, although two key medicines used in second-line treatment, atazanavir/ritonavir and lopinavir/ritonavir, have fallen 28% this year due to competition among generic producers. Even so, the price of the least expensive second-line drug is still more than double the cost of first-line treatment. In addition, viral load testing is often costly and complex, requiring skilled technicians at a referral laboratory and sample transfer by cold chain.
As a result of these challenges, resource-poor countries tend to use CD4 counts to determine the presence of treatment failure. There are several key problems with this approach. Studies in resource-poor settings have indicated frequent discordance between CD4 counts and viral load. In some cases, a marked increase in CD4 count has occurred alongside incomplete viral suppression, and in other cases, complete viral suppression has accompanied marked decreases in CD4 count. The evidence on the usefulness of CD4 count in determining treatment response is decidedly mixed. Some studies suggest that it is not an inferior strategy to viral load testing while others equally strongly assert that CD4 testing is not a reliable strategy for detecting treatment response. In addition, viral load testing is particularly important in identifying HIV-positive newborns, since any infant born to an HIV-positive mother will be seropositive until about 12-18 months of age. It is particularly important to identify these infants and start treating them with ART as soon as possible in order to prevent opportunistic infections and complications. It is largely in response to these types of challenges that the WHO has decided to recommend viral load testing as the gold standard for determining treatment failure and resistance.
But is the WHO’s recommendation a realistic one for some of the poorest countries hardest hit by the HIV/AIDS epidemic? What needs to be done to provide better access to viral load testing in these settings? Some generic, low-cost reagents for viral load assays have been developed in recent years, and evidence suggests that they perform well in detecting treatment failure. Most of these technologies are still time-consuming and technologically complex, however. There are, nonetheless, some steps that can be taken to increase the uptake of viral load testing in resource-poor settings. Bygrave relates that MSF is starting to utilize dried blood spots as samples. Dried blood spots, which are easy to prepare and do not require transport by cold chain, can be transported to a laboratory with viral testing capacity. The use of dried blood eliminates the need for complex transportation methods.
Bygrave also highlights another key strategy: “viral load pooling,” which has the capacity to significantly reduce costs. If significant amounts of virus are detected in the pooled sample, replicating virus is assumed to be present in at least one of the patients and then individual viral load testing can be pursued.
In order to implement this type of simplified viral load testing, training tools, trainers, guidelines, consensus protocols, and monitoring and evaluation tools must be established. Variable costs must also be taken into consideration, including cost of maintenance of equipment and the cost of labor. Clinicians in developing countries must be comfortable with the accuracy of these alternative viral load testing technologies and should reach a consensus about the appropriate level of monitoring in resource-poor settings.
Is viral load testing an essential component of HIV treatment? Experts seem to disagree on this question. “ART saves lives without it,” says Hallett, suggesting that viral load testing is “certainly helpful” but “perhaps not always essential.” According to Hallett, resources should not be expended on viral load testing if it is at the expense of resources for expanding ART coverage. For Bygrave, viral load testing should be “routine.” According to Bygrave, although access to ART should be the priority, waiting for clinical failure to begin viral load monitoring is waiting too long. In addition, spending money on CD4 testing, with its “extremely poor positive predictive value,” does not seem like the best strategy if one viral load test can be equal in cost to two CD4 tests. “The purpose of viral load testing is so that we can catch poor adherers early and intervene,” she says. In the meantime, MSF and other international humanitarian aid and medical organizations are working on methods to make viral load testing more feasible in developing countries.
A correction was made to this blog post on 3rd March 2014. The sentence “In addition, spending money on CD4 testing, with its ‘extremely poor positive predictive value,’ does not seem like the best strategy if two viral load tests can be equal in cost to one CD4″ now reads: “In addition, spending money on CD4 testing, with its ‘extremely poor positive predictive value,’ does not seem like the best strategy if one viral load test can be equal in cost to two CD4 tests.”