Full results of DART lab monitoring study published

Full results of the DART study of laboratory monitoring of antiretroviral treatment are published today in The Lancet.

The results of the DART study, which showed that patients who did not undergo routine CD4 cell or drug toxicity laboratory monitoring were only marginally more likely to experience disease progression or die while receiving antiretroviral therapy during a five-year study in Zimbabwe and Uganda, were first presented at the International AIDS Society conference in Cape Town in July.

The study was designed to determine whether antiretroviral therapy could be implemented safely and effectively in a resource-limited setting without routine use of expensive laboratory tests.

Tests to monitor the immune system response (CD4 count) to antiretroviral therapy require specialised laboratory equipment, chemicals and trained staff that may be out of reach of many health facilities outside large cities.

These tests also force additional charges on patients, even when antiretroviral therapy is free, imposing a significant financial burden on patients. People with HIV may also be required to travel long distances to hospital if antiretroviral therapy is only prescribed at clinics equipped to carry out these tests.

In the DART study participants were randomised either to receive treatment with routine laboratory monitoring, or to receive treatment with clinical monitoring supported by laboratory tests only where the clinician needed more information about a patient’s condition in order to make a clinical decision, or where a grade 4 toxicity was detected.

Key findings of the study include:

• After five years 90% of the routine laboratory monitoring group were still alive, compared with 87% of the clinical monitoring group (hazard ratio = 1.35 (95% confidence interval 1.10-1.65), p=0.004).
• People in the clinical monitoring arm were around 30% more likely to experience disease progression or to die (hazard ratio 1.31 [95% CI 1.14 – 1.51], p=0.0001).
• It would have been necessary to monitor CD4 counts in 59 patients for one year to prevent one new WHO stage 4 event.
• Differences in disease progression became apparent only after the second year of treatment was completed, leading the investigators to suggest that routine monitoring of CD4 counts is likely to be of greater value from year three of antiretroviral treatment onwards.
• There was no significant difference in the rate of serious adverse events between the two study arms

However the study results are unable to show the outcomes of patients in each arm who switched to second-line treatment, and to show whether there is any difference in long-term outcomes as a result of earlier or later treatment.

In a policy briefing also issued on December 9th the DART trial investigators make a number of policy recommendations based on the results of the study.

• Priority should be given to widening access to first and second-line drugs to treat HIV infection.
• Resources are best focused on strengthening healthcare systems (including laboratories for diagnosing acute illnesses) and training healthcare workers to deliver high quality care in rural areas. This benefits the health infrastructure for all, not just those with HIV.
• Monitoring disease progression with CD4 counts is of measurable but relatively small benefit which was only seen after the second year of ART. For CD4 monitoring to be practical and cost-effective resources should be given to develop cheaper, point-of-care CD4 tests. This will also aid initial diagnoses of HIV and help to inform when treatment should be started.
• Routine monitoring for the side-effects of ART is costly and of no additional benefit over and above clinical monitoring of the patient. Routine haematology and biochemistry testing should not be considered an essential element of HIV treatment in resource-limited settings.
• Efforts should also be focused on ensuring long term adherence to ART.