Trial on arv holiday fails
Mar 28, 2006
Uganda and Zimbabwe were the two countries in Africa hosting a trial on antiretroviral treatment (ART) holiday. People on ART were given days off the antiretrovirals (ARVs) to monitor whether having a break in the otherwise daily dosage would work without serious side effects and drug resistance. Th
The Medical Research Council (MRC), Entebbe has stopped the ARV Holiday programme, saying many participants were developing clinical HIV- related diseases. Ordinarily, people living with AIDS are supposed to take ARVs on a daily basis, but under the ARV Holiday programme, patients would take a break from ARVs for a given number of days or weeks. The trial was carried out by Dart, funded by MRC, the Rockefeller Foundation as well as DFID and coordinated by scientists from Kampala, Harare, and the Imperial College London and the MRC Clinical Trials Unit.
The patients who were enrolled for ART Holiday have since been moved to Continuous Therapy (CT). However, the random trial of different strategies for the clinical management of ART, the main purpose of the Dart trial, continues.
The decision was made following review of data by an independent Data and Safety Monitoring Committee (DSMC), which was regularly reviewing trial progress and safety issues during the five-year trial.
DSMC revealed early this month that interim data from 799 patients demonstrated a greater rate of clinical HIV- related diseases in patients undergoing fixed length (12 weeks on ART, 12 weeks off ART) compared to patients on CT. The press release from The Dart Trial said that although most of these disease episodes in the people on ART holiday were treatable and did not require hospitalisation, the difference between patients who interrupted therapy and those who did not was considered clinically important.
The data also suggests that the strategy carried an increased risk of clinical symptoms in patients who had low CD4 counts and multiple illnesses before they started ART and cannot be recommended.
The US government recently stopped similar trials saying participants were likely to become ill or die if they took breaks. Participants developed major complications such as cardiovascular, kidney and liver diseases. The statement from National Institute of Allergy and Infectious Diseases (NIAID) said the trial quickly showed that patients did better when they continuously took ARVs.
In Uganda the Dart Trial is carried out by Joint Clinical Research Centre (JCRC), Kampala and at MRC Entebbe. The JCRC trial had a two-day holiday every week while at Entebbe Grade A, it was a holiday for 12 weeks.
The University of Harare in Zimbabwe also reported similar findings. According to Dr. Heiner Grosskurth, the director of MCR, the three centres in Uganda and Zimbabwe used the same principle and had 3,300 patients on Dart trial.
One participant at the Dart Trial Entebbe Grade A, who has been on the holiday trial since 2004, had complained of having side effects whenever he got ARV holiday. He said as soon as the ARV holiday started (for three months), his CD4 cell count would fall, he would lose his appetite and energy, would develop malaria, cough, backache and chest pain. He said he would also become weak and feel dizzy. These side effects would disappear the moment he resumed the drugs.
He said whenever he complained, the doctors would treat the infections and assure him that the trial was not dangerous. A number of participants had developed similar side effects and abandoned the project. Heiner said participants were encouraged to report anything that made them feel unwell.
Dr. Godfrey Kabuye of JCRC said their group (of taking drugs for five days and two days holiday) had not had serious problems.
Ends
The patients who were enrolled for ART Holiday have since been moved to Continuous Therapy (CT). However, the random trial of different strategies for the clinical management of ART, the main purpose of the Dart trial, continues.
The decision was made following review of data by an independent Data and Safety Monitoring Committee (DSMC), which was regularly reviewing trial progress and safety issues during the five-year trial.
DSMC revealed early this month that interim data from 799 patients demonstrated a greater rate of clinical HIV- related diseases in patients undergoing fixed length (12 weeks on ART, 12 weeks off ART) compared to patients on CT. The press release from The Dart Trial said that although most of these disease episodes in the people on ART holiday were treatable and did not require hospitalisation, the difference between patients who interrupted therapy and those who did not was considered clinically important.
The data also suggests that the strategy carried an increased risk of clinical symptoms in patients who had low CD4 counts and multiple illnesses before they started ART and cannot be recommended.
The US government recently stopped similar trials saying participants were likely to become ill or die if they took breaks. Participants developed major complications such as cardiovascular, kidney and liver diseases. The statement from National Institute of Allergy and Infectious Diseases (NIAID) said the trial quickly showed that patients did better when they continuously took ARVs.
In Uganda the Dart Trial is carried out by Joint Clinical Research Centre (JCRC), Kampala and at MRC Entebbe. The JCRC trial had a two-day holiday every week while at Entebbe Grade A, it was a holiday for 12 weeks.
The University of Harare in Zimbabwe also reported similar findings. According to Dr. Heiner Grosskurth, the director of MCR, the three centres in Uganda and Zimbabwe used the same principle and had 3,300 patients on Dart trial.
One participant at the Dart Trial Entebbe Grade A, who has been on the holiday trial since 2004, had complained of having side effects whenever he got ARV holiday. He said as soon as the ARV holiday started (for three months), his CD4 cell count would fall, he would lose his appetite and energy, would develop malaria, cough, backache and chest pain. He said he would also become weak and feel dizzy. These side effects would disappear the moment he resumed the drugs.
He said whenever he complained, the doctors would treat the infections and assure him that the trial was not dangerous. A number of participants had developed similar side effects and abandoned the project. Heiner said participants were encouraged to report anything that made them feel unwell.
Dr. Godfrey Kabuye of JCRC said their group (of taking drugs for five days and two days holiday) had not had serious problems.
Ends