Comparative efficacy and safety of raltegravir-based simplified regimens for people living with HIV infection: a systematic review and meta-analysis
The Lancet(2018)
摘要
Abstract Background Simplifying antiretroviral therapy (ART) enhances tolerability, decreases toxicities, and reduces costs. However, more evidence is still needed to show the benefit and risk of simplified ART regimens. Therefore, we aimed to evaluate the efficacy and safety of simplified ART regimens based on raltegravir for people living with HIV infection. Methods We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We systematically searched PubMed, MEDLINE, Web of Science, and Embase from their inception to Jan 31, 2018, using the following search terms: “HIV”, “protease inhibitor”, and “raltegravir” in English. We identified raltegravir-based RCTs containing only two drugs; we subsequently compared the efficacy and safety between raltegravir-based simplified regimens with traditional protease inhibitor-based three-drug or four-drug regimens. Primary measures included viral suppression, CD4 cell counts, and adverse events. We pooled data across studies and estimated summary effect sizes using an intention-to-treat (ITT) analysis and per-protocol (PP) analysis. The included data were analysed with Review Manager (version 5.3). Findings We identified and included eight RCTs involving 4420 patients with HIV-1 infection, of whom 2187 (49·5%) patients who were receiving raltegravir plus ritonavir-boosted protease inhibitors were compared with 2144 (48·5%) patients receiving ritonavir-boosted protease inhibitors plus two or three nucleoside reverse-transcriptase inhibitors (NRTIs). The proportion of viral suppression of raltegravir-based simplified regimens was 77% (95% CI 73–80 for the ITT analysis) and 81% (95% CI 71–91 for the PP analysis) at 24 weeks, 79% (71–87; ITT) and 75% (70–81; PP) at 48 weeks, and 74% (61–86; ITT) and 82% (70–93; PP) at 96 weeks. The proportion of viral suppression of ritonavir-boosted protease inhibitors plus two or three NRTIs was 69% (95% CI 65–74 for the ITT analysis) and 70% (95% CI 53–88 for the PP analysis) at 24 weeks, 78% (70–86; ITT) and 73% (68–79; PP) at 48 weeks, and 71% (61–82; ITT) and 80% (71–89; PP) at 96 weeks. At 24 weeks, the efficacy of raltegravir-based two-drug regimens was greater than that of ritonavir-boosted protease inhibitors plus two or three NRTIs (ITT analysis: risk ratio 1·11, 95% credible interval 1·02–1·21; p=0·01). Patients had significantly higher CD4 cell counts than those receiving NRTIs-based three-drug or four-drug regimens at 48 weeks and 96 weeks. Raltegravir-based simplified regimens had less grade 3 or 4 adverse events than traditional NRTIs-based regimens at 48 week (p=0·007). Interpretation The results of this systematic review and meta-analysis supported that regimens containing raltegravir plus ritonavir-boosted protease inhibitors were non-inferior to regimens containing ritonavir-boosted protease inhibitors plus two or three NRTIs in viral suppression. However, simplified regimens resulted in better CD4 cell count concentrations and lower numbers of adverse events. Funding The National Science and Technology Major Project of China During the 13th Five-year Plan Period (2018ZX10302104001), Chinese Medicine Science and Technology Project (number ZY201702047), Chinese Government 13th Five-year Plan (2017ZX10201101), Major Project of Beijing Municipal Science and Technology Committee (D161100000416003), and The National Natural Science Foundation of China (81701984).
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