SMART study examines the long term benefit risk of interruptions versus continued use of ART
The following letter was received from Jens D Lundgren and others.
In the July issue of HTB, Simon Collins raised concerns regarding the potential of emergence of resistance in patients discontinuing an NNRTI-based ART regimen, and he was asking for guidelines for how to diminish the risk of this in the SMART study.
The SMART protocol team shares the concerns being expressed in the article. Immediately after the data were first presented at CROI, we drafted a set of guidelines on strategies to diminish this risk.
The preferred strategy is to switch to a PI-based regimen 3 weeks before discontinuation to allow for complete removal of the NNRTI when ART is discontinued. Although this strategy is not based on formal clinical studies, it is the best advice available at the present time. We plan to update the guidelines as new information emerges.
The SMART study plans to enrol and randomise 6,000 patients to one of two strategies of using ART:
- the viral suppression strategy where ART is used at all times to suppress HIV replication to the largest extent possible (current state-of-the-art);
- the drug conservation strategy where ART is only used intermittently to maintain a CD4 count in the range of 200-350 cells/mm3.
The study will proceed for the next 5-7 years and hence allow for a profound understanding of the longer-term implications of the two treatment strategies to be compared. A present, 2,050 of the 6,000 patients have been enrolled, and we expect that a large number of patients from across Europe will enrol in the study over the next year.
Yours sincerely, Jens D. Lundgren & Ulrik B Dragsted (Copenhagen coordinating centre), Adrian Palfreeman, Abdel Babiker & Janet Darbyshire (London coordinating centre).
The SMART study addresses important and compelling questions over long term management of treatment and has been developed with strong community input and support.
The study protocol for stopping treatment provides current best practice for any patient considering stopping an NNRTI or 3TC-based treatment. As such the guidance is also worth considering for patients stopping treatment for any reason, whether or not they are in this study.