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Structured treatment
interruptions (STIs) versus continuous therapy in DART
One of the initial aims of the DART trial was to assess
if antiretroviral (ARV) drugs could be given intermittently rather than
continuously to provide a similar level of benefit to patients but with
less associated toxicity. In Africa questions about STIs are especially
relevant as there are currently limited resources for provision of
antiretroviral therapy (ART) and laboratory monitoring. If STIs were
feasible, even in some cases, without risking harm to an individual,
then those resources could be stretched further and enable more people
to be treated successfully. When DART started there was no information
available about STIs in Africa and it was agreed that this was an
important question that could be addressed within the study.
The structured treatment interruptions (STIs) of 12 weeks on and 12
weeks off drugs versus continuous therapy randomisation opened in July
2004 after a non-randomised pilot study of 100 patients. All
participants on STIs moved back to continuous ARVs after the STI study
closed in March 2006. There were a similar number of deaths among those
who interrupted treatment (5 deaths) and those who continued treatment
at all times (4 deaths) but in total for every 100 participants on STIs
for a year, 9 would become seriously ill or die; compared to only 3
participants on continuous ARV therapy. Although the absolute number of
participants who became very ill was small, the investigators
considered the increase in risk was not acceptable.
A questionnaire completed by STI participants after the study closed
showed that about a third of participants preferred STI to continuous
therapy, one third had problems with STIs including feeling ill and
experiencing side effects when back on drugs, and one third had no
preference.
Trial protocol
137 DART participants took part in the non-randomised STI pilot during
late 2003 and early 2004. Entry was based on achieving CD4>200
cells/mm3 at week 24, this was increased to CD4>250 cells/mm3
in November 2003 due to higher than anticipated measurement variability
of CD4. Three patients out of 137 died during the STI pilot (2.4 per
cent). Based upon the high CD4 variability and event rate, the
threshold for the STI trial was changed to CD4>300 cells/mm3.
813 DART participants were randomised to STIs or continuous therapy
between July 2004 and March 2006. Entry was based on achieving
CD4>300 cells/ mm3
at 48 or 72 weeks. The Data and Safety Monitoring Committee (DSMC) and
DART Trial Steering Committee (TSC) took the decision to move all
patients to continuous therapy in March 2006. Data was unblinded after
STI termination and revealed that nine patients out of 813 died during
the randomised trial; five in the STI arm and four in the continuous
therapy arm. Four patients were lost to follow-up; three in the STI arm
and one in the continuous therapy arm.
STI publications & presentations
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