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

摘要: Background Structured treatment interruptions (STI) of antiretroviral therapy (ART) have been investigated as part novel strategies, with different aims and objectives depending on the populations involved. These include: 1) patients who initiate ART during acute HIV infection; 2) chronic infection, ART, successfully suppressed viremia; 3) infection failure, persistent viremia due to multi-drug resistant (Hirschel 2001; Deeks 2002; Miller 2003). In an earlier Cochrane review (Pai 2005), we had summarized evidence about effects STI in infection. this review, summarize unsuppressed drug-resistant HIV. Unsuppressed describes those cannot suppress viremia, presence multi-drug-resistant virus. It is also referred failure. Drug resistance identified by mutations at baseline.STI a strategy HIV-infected involves interrupting controlled clinical settings, for pre-specified duration time. various aims, including following: allow wild virus re-emerge replace mutant virus, hope improving efficacy subsequent regimen; halt development drug preserve options; alleviate fatigue reduce drug-related adverse effects; 4) improve quality life (Miller 2003; Montaner Vella 2000;). Objectives The objective our systematic was synthesize effect structured adult Search We included all available intervention studies (randomized trials non-randomized trials) conducted worldwide. searched nine databases, covering period from January 1996 February 2006. scanned bibliographies relevant contacted experts field identify unpublished research, abstracts ongoing trials. first screen, total 3186 potentially eligible citations databases sources were identified, which 2047 duplicate excluded. remaining 1139 examined detail, further excluded 951 that modeling studies, animal case reports, opinion pieces. As shown Figure 01, 188 second screen full-text screening. Of these, 60 basic science editorials 128 articles retrieved. third eligibility review. subclassified into three categories: Studies if their did not contain enough information inclusion reviews. A 62 finally classified suppressed, acute, categories. 17 met criteria Selection Inclusion criteriaAll randomized or investigating planned among Early pilot prospective fixed variable durations included. Relevant they contained sufficient information. Exclusion criteriaEditorials, reviews, separate primary beyond scope Data collection analysis Two reviewers independently extracted data, evaluated study quality. Disagreements resolved consultation reviewer.A seventeen However, significant heterogeneity across (i.e. design, populations, baseline characteristics, reported outcomes; reporting measures effect, hazard ratios, risk ratios), considered it inappropriate perform meta-analysis. Main results early trials, pattern evident studies. During interruption, decline CD4 cell counts, increase viral load, shift level genotypic towards more wild-type reported. This suggests may be used susceptibility optimized salvage regimen upon re-initiation. generated useful data hypotheses later tested Randomized rated high eight reviewed, seven completed while one remains blinded. six consistent virologic immunologic patterns, found no benefit response arm, compared control arm. addition, largest trial greater numbers disease progression events prolonged negative impact counts arm (Beatty 2005; Benson 2004; Lawrence Walmsley Ruiz single RCT divergent findings others (GigHAART), STI, prescribing shorter 8-9 drugs. There differences patient population characteristics study, targeting very advanced (Katlama 2004). Although await unblinded eighth (OPTIMA), so far does support setting failure (Brown Holodniy Kyriakides Singer 2006). Authors' conclusions current primarily supports lack before switching despite ART. harm attempting relatively disease, associated increased progression. At time, there recommend use category