Structured treatment interruptions (STI) in chronic unsuppressed HIV infection in adults

Background Structured treatment interruptions (STI) of antiretroviral therapy (ART) have been investigated as part of novel treatment strategies, with different aims and objectives depending on the populations involved. These populations include: 1) patients who initiate ART during acute HIV infection; 2) patients with chronic HIV infection, on ART, with successfully suppressed viremia; and 3) patients with chronic HIV infection and treatment failure, with persistent viremia due to multi‐drug resistant HIV (Hirschel 2001; Deeks 2002; Miller 2003). In an earlier Cochrane review (Pai 2005), we had summarized the evidence about the effects of STI in chronic suppressed HIV infection. In this review, we summarize the evidence on STI in patients with chronic unsuppressed HIV infection due to drug‐resistant HIV. Unsuppressed HIV infection describes those patients who cannot suppress viremia, due to the presence of multi‐drug‐resistant virus. It is also referred to as treatment failure. Drug resistance is identified by the presence of resistant mutations at baseline. STI as a treatment strategy in HIV‐infected patients with chronic unsuppressed viremia involves interrupting ART in controlled clinical settings, for a pre‐specified duration of time. These interruptions have various aims, including the following: 1) to allow wild virus to re‐emerge and replace the resistant mutant virus, with the hope of improving the efficacy of a subsequent ART regimen; 2) to halt development of drug resistance and to preserve subsequent treatment options; 3) to alleviate treatment fatigue and reduce drug‐related adverse effects; and 4) to improve quality of life (Miller 2003; Montaner 2001; Vella 2000;). Objectives The objective of our systematic review was to synthesize the evidence on the effect of structured treatment interruptions in adult patients with chronic unsuppressed HIV infection. Search methods We included all available intervention studies (randomized controlled trials and non‐randomized trials) conducted in HIV‐infected patients worldwide. We searched nine databases, covering the period from January 1996 to February 2006. We also scanned bibliographies of relevant studies and contacted experts in the field to identify unpublished research, s and ongoing trials. In the first screen, a total of 3186 potentially eligible citations from nine databases and sources were identified, of which 2047 duplicate citations were excluded. The remaining 1139 citations were exam