Background: Ritonavir-boosted protease-inhibitor (PI)-monotherapies are an attractive alternative to conventional therapy in order to avoid the potential mitochondrial toxicity and lipoatrophy associated with NRTI drugs. We carried out a systematic review and meta-analysis of clinical trials evaluating the effectiveness and safety of strategies using induction with two NRTI and one PI/r and maintenance with one PI/r. Methods: Literature review in electronic databases and proceedings and abstracts from major Conferences in Infectious Diseases and HIV infection. Studies were included in the analysis if 1) Patients were treated with Ritonavir-boosted protease-inhibitor (PI)- monotherapy after achieving complete virological suppression with standard 3-drug regimen, 2) Follow-up was at least 24 weeks and 3) Virological failure and discontinuation rate was reported at the end of follow up. Analysis was carried out by intention-to-treat (Missing=failure). Results: We identified a total of 13 studies. In 9 single arm studies (3 ATV/R, 2 LPV/R and 1 IDV/R) recruiting a total of 115 patients with follow-up from 24 to 48 wks, there were 20 patients with virological failure in patient-year follow-up (Failure rate per 100 patient-years; 95% CI: to 41.23). In 4 randomized clinical trials (4 LPV/R) recruiting a total of 462 patients with follow up from wks, the failure rate was 56 in 354 patient-years follow up in the intervention group vs. 27 out in 262 patient- years follow-up in the control group (Risk Difference 5.51 per 100 patients-year; 95% CI: from to 11.19; p= 0.06), with no heterogeneity among trials (I 2 =0%; p=0.54). Discontinuation due to severe side effects were 1 out from 154 (0.65%) in the intervention group vs. 4 out from 153 (2.61%) in the control group (Relative Risk: 0.49: 95% CI: ; p=0.43), with no heterogeneity among trials (I 2 =0.4%; p=0.37) Conclusion: Switching from triple drug therapy to ritonavir-boosted protease-inhibitor monotherapies in patients who were virologically suppressed is less effective than standard HAART. Antiretroviral Treatment Simplification to Ritonavir-boosted Protease Inhibitor Monotherapy: Systematic Review and Meta-analysis Javier Ena, Francisco Pasquau, Rosa F. Ruiz-de-Apodaca Hospital Marina Baixa. Alicante. Spain MethodsAbstract (Updated) Objectives Results Conclusions References 1.Arribas JR. J. of AIDS 2005; 40:280 2.Cameron DW. J Infect Dis 2008; 198:234 3.Campo RE. AIDS 2005; 19:447 4.Kahlert C. AIDS 2004; 18:955 5.Karlström O. J. of AIDS 2007; 44:417 6.Moltó J. J Antimicrob Chemother 2007; 60:436 7.Nunes EP. 11 EACS, Oct 2007, Abstract P7.5/04 To assess the effectiveness of ritonavir-boosted protease inhibitor monotherapy to maintain virological suppression in patients who had HIV RNA below the detection limit. Switching from triple drug therapy to ritonavir-boosted protease-inhibitor monotherapy in patients who are virologically suppressed is less effective than standard HAART. Correspondence: Searching: MEDLINE, EMBASE, Conference Reports Index, Cochrane Controlled Trails Register, Cochrane Database of Systematic Reviews. A search strategy was developed with an aid of an expert librarian. In addition, a hand search was carried out to identify unpublished information from the most important conferences on HIV and infectious diseases. Selection: Single-arm trials and randomized controlled trials. (Population: HIV-infected patients with HIV RNA not detectable at study entry; Intervention: Treatment with ritonavir-boosted single protease-inhibitor therapy, Principal outcome: virological failure as it was defined in each study. Data abstraction: process of data completed independently, in duplicate. Quantitative data synthesis: Single arm studies principal measures of effect (failure rate by 100 patient-years of follow-up with 95% confidence intervals) (OpenEpi calculator). Analysis as intention to treat (missing=failure) and as per-protocol (virological failure=failure). Randomized clinical trials principal measures of effect (Relative Risk failure rate at end of follow-up) (RevMan 4.2). 8. Pierone G. HIV Clin Trials 2006; 7: Pulido F. AIDS 2008; 22; F1 10. Pulido F. J Antimicrob Chemother 2008; 61: Sprinz E. HIV Medicine 2008; 9: Swindells S. JAMA 2006; 296: Vernazza P. AIDS 2007; 21:1309 Results