DART: Development of AntiRetroviral Therapy in Africa - A randomised trial of monitoring practice and structured treatment interruptions in the management of antiretroviral therapy in adults with HIV infection in Africa
A trial to learn more about how useful routine laboratory tests are when using anti-HIV drugs
What is this study about?
DART was a clinical trial about the best ways to manage anti-HIV therapy in the public health access programmes being rolled-out in Africa and other resource-limited settings. It was designed to address two main questions:
1. Can doctors prescribe anti-HIV drugs without doing regular routine laboratory tests, and instead rely on clinical assessments they can make themselves and only do tests when needed? (Laboratories are scarce in some parts of Africa, and the tests can be very expensive. How much of the money for access programmes should be spent on doctors, nurses and drugs and how much on laboratories, technicians and tests?)
2. Is taking anti-HIV drugs some of the time as effective as taking them continuously?
In order to answer question 1, all participants had laboratory safety tests carried out every 3 months. But doctors were not routinely given the results for one group of patients. Instead they had to rely more on clinical observations when managing these patients. Where the doctors felt there was a specific clinical need they could ask for any relevant laboratory tests. In order to minimise any unnecessary risks to participants in this group, the routine test results were always sent to doctors if they suggested there may have been a serious problem, in case the problems had not been identified clinically. Additionally, only the group getting regular routine tests received CD4 counts every 3 months, the other group never received CD4 counts.
CD4 counts are used to indicate how well the immune system is working and are often used to identify when anti-HIV drugs are no longer working so well. To answer question 2 above, patients who responded well to initial treatment were randomly assigned to either keep taking their anti-HIV drugs all the time, or to move on to cycles of 12 weeks on and 12 weeks off drugs.
DART was the largest trial of its kind in Africa, and one of the first HIV trials to take place in more than one African country and in a number of different clinics. It was run by researchers in Uganda and Zimbabwe, collaborating with Imperial College London and the MRC Clinical Trials Unit.
Who is included?
DART recruited 3,320 people with advanced HIV disease or AIDS.
When is it taking place?
This trial recruited people between 2003 and 2004. Participants were treated, cared for and followed through to the end of 2008, with phased and managed transition to national treatment programmes in 2009.
Where is it taking place?
In Uganda and Zimbabwe
Who is funding the study?
Medical Research Council, DFID, Rockefeller Foundation. Antiretroviral drugs donated by Gilead Sciences, GlaxoSmithKline, Boehringer-Ingelheim and Abbott Labs. Gilead, GlaxoSmithKline and Abbott have also provided some funding for some substudies of DART
|Type of study:||Randomised trial|
|MAMS||This is a multi arm multi stage study|
|Study start date:||January 2003|
|Study end date:||31-Mar-09|
|Randomisations achieved:||3316, as of October 2004|
|Also included in this study:||Health Economics|
Quality of life outcomes
|Inclusion criteria:||1. Documentation of HIV-1 infection: antibody positive serology by enzyme-linked immunosorbent
assay (ELISA) test (confirmed by licensed second ELISA or Western Blot)
2. Age =18 years
3. Symptomatic WHO stage 2, 3 or 4 HIV disease and CD4 <200 cells/mm3
4. ART naïve (except for ART use during pregnancy for the prevention of mother-to-child HIV transmission)
5. Agreement and documented informed consent to be randomised to CMO or LCM and to STI or continuous ART, if eligible
6. Life expectancy of at least 3 months|
|Exclusion criteria:||1. Cannot or unlikely to attend regularly (e.g. usual residence too far from Study Centre)
2. Likelihood of poor compliance
3. Presence of acute infection (e.g. malaria, acute hepatitis, pneumococcal pneumonia, non-typhoid salmonella septicaemia, cryptococcal meningitis). Patients may be admitted after recovery of an acute infection. Patients with tuberculosis (TB) will not be enrolled while on the intensive phase of anti-tuberculosis therapy, but should be re-evaluated after the intensive phase and a decision made then about starting ART. Patients starting ART whilst on anti-tuberculosis therapy after the intensive phase will not receive NVP, nor will they be randomised into the NORA substudy.
4. On chemotherapy for malignancy
5. Laboratory abnormalities which are a contraindication for the patient to start ART (e.g. haemoglobin <8 g/dl, total white blood cell count [WBC] <0.75 x 10^9/l, aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >5 x the upper limit of normal [ULN], grade 3 renal dysfunction - creatinine >360 µmol/l and/or urea >5 x ULN)
6. Pregnancy or breast-feeding|
|Intervention and control groups:||Diagnostics|
|Method of randomisation:||Stratification with blocking|
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