The treatment interruption arm of a major clinical trial has been terminated after it was found that patients who were randomised to cycles of HIV treatment followed by treatment breaks were more likely to experience HIV-related illnesses.
Individuals who had been enrolled into the treatment interruption arm of the DART (Development of Anti-Retroviral Therapy in Africa) study will now take continuous antiretroviral therapy. However, the study will continue with its primary objective of assessing two methods of monitoring patients receiving antiretroviral therapy in Africa.
This is the second major treatment interruption trial to be terminated this year. In January, the SMART study, which was looking at the safety of CD4 guided treatment interruptions was terminated after the study investigators found that patients taking a treatment break were significantly more likely to experience a clinical event.
A total of 799 patients were included in the treatment interruption sub-study of DART. These individuals had experienced an increase in their CD4 cell count to above 300 cells/mm3 after twelve to eighteen months of starting antiretroviral therapy and were randomised to either take continuous antiretroviral therapy or to take twelve weeks cycles of treatment followed by twelve week interruptions.
The decision to terminate the treatment interruption arm of the DART study was made by the trial’s steering committee after interim analysis by the study’s independent Data Safety and Monitoring Committee found that individuals who were randomised to take cycles of treatment followed by a break were significantly more likely to experience an HIV-related illness.
The rate of HIV-related illness was 2.0 per 100 patient years in individuals who received continuous anti-HIV therapy, but 8.6 events per 100 patient years in individuals who took treatment breaks. There were two deaths, one in each arm of the study. Most of the illnesses seen in patients in the treatment interruption arm of the study were treatable and did not require hospitalisation, the most common being oesophageal candidiasis (thrush in the throat or gullet).
Investigators concluded that the DART intermittent treatment strategy carried an increased risk of illness, and therefore could not be recommended, for individuals who started antiretroviral therapy with a CD4 cell count below 200 cells/mm3 or who had a history of multiple HIV-related illnesses.
Nevertheless, the investigators do not believe that this is the death knell for treatment interruptions, commenting in a press statement, “the need to interrupt [HIV] therapy for multiple reasons, e.g. drug toxicity, is likely to remain an integral part of life-long treatment for HIV disease. Finding out how and when therapy can be interrupted safely and which patients may benefit from such strategies are still important questions and should be pursued in future trials."
The DART study will continue to evaluate two strategic approaches to the management of antiretroviral therapy in Africa: clinical monitoring alone versus laboratory and clinical monitoring. The study is coordinated by the UK's Medical Research Council Clinical Trials Unit, clinical sites in Uganda and Zimbabwe, and by Imperial College, London.
Further results will be presented to the International AIDS Conference in Toronto this August.