Treatment failure going undetected

Too many HIV-infected patients in Africa are dying due to the difficulty of diagnosing and managing antiretroviral treatment (ART) failure in resource-limited settings.

According to an opinion piece co-authored by several AIDS experts, which appears in the latest issue of British medical journal, The Lancet, the current criteria for detecting ART failure in Africa are "unreliable", with many patients going undetected and others being switched to more expensive second-line treatment unnecessarily, "at great cost to individuals, and to programmes".

Most low-income countries lack the resources or the manpower to monitor patients on ART through the use of regular laboratory testing as is standard practice in high-income countries. In Malawi, for example, where only about one in four ART clinics have facilities to conduct CD4-cell counts (a measure of immune system strength) and even fewer can do viral load testing (a measure of the amount of HI virus in the blood), health workers mainly rely on clinical symptoms to detect treatment failure.

But as the authors note, "ART clinics are usually busy and understaffed...In these circumstances, thorough clinical assessment is often impossible and new clinical conditions might be missed."

Out of nearly 200,000 patients initiated on ART in Malawi by the end of 2008, 12 percent were known to have died and a further 12 percent were "lost to follow up", meaning they had not returned to a clinic for at least three months. Although nearly two-thirds of the deaths occurred within three months after starting ART as a result of starting treatment too late, the authors note that an increasing proportion of patients were dying later, most likely after developing resistance to first-line drugs and contracting HIV-related diseases.

Clinical assessment can also be misleading, with symptoms of drug toxicity easily confused with those of certain opportunistic infections. Several recent studies have found that many patients are incorrectly diagnosed as having treatment failure and needlessly put on second-line ART.

Commenting on recent results from the Development of Antiretroviral Therapy in Africa (DART) trial, which found that laboratory monitoring provided little additional benefit compared to clinical monitoring alone for patients in their first two years of treatment, The Lancet authors argue that the findings "do not take into account the poor performance of current clinical monitoring in routine practice".

They write that there is an urgent need for a tool to diagnose ART failure that would be simple for staff at busy, undermanned clinics to use. One solution could be a rapid, viral-load test similar to that used for diagnosing HIV that relies on finger-prick blood sampling. The development of such a test could revolutionise ART management.

The authors' second recommendation is for simpler, second-line ART regimens that could be administered by the lower-cadres of health workers who will be needed to manage an ever growing number of patients on life-long treatment.

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One possibility already being tested in several clinical trials, is to use a single class of antiretroviral drug known as a boosted protease-inhibitor. Monotherapy for second-line ART would minimise drug costs, reduce health-care provider error and improve adherence, but needs further testing.

The authors conclude that building on the enormous progress made in scaling up ART in sub-Saharan Africa will require "simple, robust systems...to protect health services from being overwhelmed".

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