Background: Structured treatment interruption (STI) of antiretroviral therapy (ART) could potentially reduce cost and toxicity, but clinical efficacy requires evaluation. Methods: An assessment of fixed-duration STI was nested in DART, a multicentre trial comparing strategies for monitoring ART in Uganda and Zimbabwe (ISCRTN 13968779). Of 3316 ART-naive symptomatic adults with CD4 cell count = 300 cells/μl after 48 or 72 weeks underwent a second randomization to either STI, cycles of 12 weeks on/off (408), or continuous ART (CT; 405). Results: Median age at STI/CT randomization was 37 years (range, 19-67) and CD4 cell count 358 cells/μl (range, 300-1054). A second review terminated the STI/CT randomisation on 15 March 2006, and participants changed to CT. Median follow-up was 51 weeks (range, 0-85): 99% and 50% of time was spent on ART in CT and STI, respectively. First new World Health Organization (WHO) stage 4 events or death occurred more frequently in STI (24; 6.4/100 person-years) than CT (9; 2.4/100 person-years) (hazard ratio, 2.73; 95% confidence interval, 1.27-5.88; P = 0.007); oesophageal candidiasis being the most frequent event (STI, 13; CT, 3). Nine (1%) participants died (STI, 5; CT, 4). There was no difference in time to first serious adverse event (P = 0.78), although ART change owing to toxicity occurred more with CT (10; 2.6/100 person-years) than with STI (2; 0.5/100 person-years) (P = 0.02). Conclusions: Although absolute rates of WHO stage 4 events/death were low, 12 week STIS initiated at a CD4 cell count >= 300 cells/μl resulted in a greater than twofold increased relative rate of disease progression compared with continuous therapy in adult Africans initiating ART with advanced disease, and cannot be recommended.
AIDS (2008) 22 (2) pp. 237-234.