Ananworanich J, Nuesch R, Le Braz M, et al. AIDS. 2003;17:F33–F37Although highly active antiretroviral therapy (HAART) has dramatically improved the duration and quality of life of human immunodeficiency virus (HIV)-infected individuals, an increasing number of serious complications are being identified among patients who are treated with these agents for long periods of time. Strategies that reduce the total drug exposure among infected patients while maintaining the stability of HIV and T cell levels would be welcomed. Scheduled or structured treatment interruptions are being evaluated in an effort to decrease the costs and side effects of HAART.In this study, 600 patients receiving successful HAART were randomized to either continuous therapy, CD4+ T cell count-guided therapy, or 1 week on/1 week off therapy.This report described the preliminary analysis of data for the 1 week on/1 week off arm. Of 36 evaluable patients, 19 had 2 successive HIV RNA plasma concentrations of >500 copies/mL after 1 week off therapy; those cases were classified as virologic failures. Most of the patients who experienced failure were receiving didanosine, stavudine, saquinavir, and ritonavir. Among those patients, there was no evidence of mutations suggesting drug resistance. Plasma saquinavir levels were within the expected range.The 1 week on/1 week off schedule tested in this study showed an unacceptably high failure rate and was therefore terminated early.Early anecdotal reports suggested that HIV-specific immune responses were boosted after discontinuation of therapy. Clinical trials based on this concept were developed for both acute and chronic HIV infections. The most promising results were from studies involving subjects who were treated for acute HIV infections; specific T cell responses to HIV were enhanced after interruptions in therapy. Similar findings have not been demonstrated for patients with chronic HIV infections. The results of this study are certainly disappointing. However, the definition of virologic failure in this study was a rebound to ≥500 copies/mL. Current guidelines suggest that HIV RNA levels of <50 000 copies/mL, with stable CD4+ T cell levels, might be acceptable. The major concern with this approach would be the development of resistance to the antiretroviral therapy if repeated rebounds were allowed to continue in the off weeks. Studies of scheduled or structured treatment interruptions will continue. Perhaps a 2 weeks on/1 week off or 3 weeks on/1 week off schedule would limit the viral rebounds and still reduce the cumulative drug exposure for patients.