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Abstract
A structured treatment interruption (STI) strategy of 12 week cycles on and off ART is clinically inferior to continuous treatment in patients with low CD4 counts before ART: a randomisation within the DART trial
Hakim J.1, on behalf of the DART Trial Team
1University of Zimbabwe, Harare, Zimbabwe, Harare, Zimbabwe
Background: Intermittent ART has the potential to reduce long-term toxicity and ART costs and improve adherence, while maintaining clinical well-being.
Methods: 3314 ART-naive adults with CD4<200 cells/mm3 from 3 sites (2 Uganda, 1 Zimbabwe) were enrolled into the DART trial: 813 with CD4300 after 48/72 weeks on ART (ZDV/3TC plus TDF, ABC or NVP) were randomised to STI (12 week cycles on/off treatment, n=408) or continuous ART (CT, n=405).
Results: At STI/CT randomisation, median age was 37 years (range 19-67), CD4 358 cells/mm3 (300-1054); CD4 nadir was 132 (1-199), 629 (77%) were receiving TDF or ABC, and 184 (23%) NVP. Following DSMC review, the STI/CT randomisation was terminated on 15 March 2006 and all patients offered continuous ART. Median follow-up at this time was 51 weeks (range 0-85): 99% of 386 person-years (PY) follow-up in CT was spent on ART, compared with 49% of 388PY in STI. Nine (1%) patients died (4CT,5STI). The rate of development of first new/recurrent WHO 4 events or death was 3.2/100PY in CT (12 patients) versus 8.3 (31 patients) in STI (HR=2.6 (95%CI 1.4-5.1), p=0.003). Oesophageal candidiasis was the most frequent first WHO 4 event (4CT,17STI), followed by extra-pulmonary TB (1CT,4STI), cryptococcosis (2CT,2STI) and herpes simplex disease (1CT,2STI). Rates of grade 4 AEs were 7.3 versus 5.9/100PY in CT and STI respectively (p=0.46): consequently ART changes for toxicity were higher in CT than STI (3.1 versus 0.5/100PY respectively,p=0.02).
Conclusions: Over median follow-up of 51 weeks, the majority (92%) of STI patients were able to take ART intermittently without developing WHO 4 events. However, the STI strategy in DART (12 week cycles after achieving CD4>300 with 12-18 months therapy in patients with pre-ART CD4<200) was associated with a 2.6-fold increased rate of disease progression, and cannot be recommended. DART continues to compare different ART monitoring strategies.
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