Full results of DART lab monitoring study published

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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.

Glossary

disease progression

The worsening of a disease.

second-line treatment

The second preferred therapy for a particular condition, used after first-line treatment fails or if a person cannot tolerate first-line drugs.

toxicity

Side-effects.

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

hazard ratio

Comparing one group with another, expresses differences in the risk of something happening. A hazard ratio above 1 means the risk is higher in the group of interest; a hazard ratio below 1 means the risk is lower. Similar to ‘relative risk’.

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.
References

DART Trial Team. Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial. The Lancet, published online December 9, 2009.