A Cochrane review [Abstract] 1 included 18 randomized and non-randomized controlled trials and 15 single arm trials with a total of 1 956 subjects. In timed-cycle structured treatment interruptions (STI) strategy, a predetermined period of fixed duration (e.g. one week, one month) off antiretroviral therapy (ART) is attempted. Timed-cycle STI fell out of favor due to reports of development of resistance in many studies. Moreover, there were no significant immunological and virological benefits, and no reduction in toxicities, reported in these studies.
In CD4-guided STI strategy, ART is interrupted for variable durations guided by CD4 levels. Participants with high nadir CD4 levels qualified for this approach. A reduction in costs of ART, a reduction in mutation, and a better tolerability of this CD4-guided STI strategy was reported. However, concerns about long-term safety of this strategy on immunological, virological, and clinical outcomes were also raised.
Currently, several large STI trials are underway, investigating long-term effects of STI strategies. Their results will be available in a few years.
Comment: The quality of evidence is downgraded by imprecise results (few patients and wide confidence intervals), by limitations in study quality (inadequate allocation concealment and follow-up) and by inconsistency (heterogeneity in interventions and outcomes).
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