1. 48-week efficacy and safety of dolutegravir relative to commonly used third agents in treatment-naive HIV-1-infected patients: a systematic review and network meta-analysis.
- Author
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Patel DA, Snedecor SJ, Tang WY, Sudharshan L, Lim JW, Cuffe R, Pulgar S, Gilchrist KA, Camejo RR, Stephens J, and Nichols G
- Subjects
- Adenine administration & dosage, Adenine analogs & derivatives, Anti-HIV Agents adverse effects, Antiretroviral Therapy, Highly Active adverse effects, CD4 Lymphocyte Count, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Dideoxynucleosides administration & dosage, Drug Combinations, Emtricitabine, HIV Infections immunology, HIV Infections virology, Heterocyclic Compounds, 3-Ring adverse effects, Humans, Lamivudine administration & dosage, Lipids blood, Lopinavir administration & dosage, Nitriles administration & dosage, Organophosphonates administration & dosage, Oxazines, Piperazines, Pyridones, Pyrimidines administration & dosage, Pyrrolidinones administration & dosage, Raltegravir Potassium, Randomized Controlled Trials as Topic, Rilpivirine, Ritonavir administration & dosage, Tenofovir, Time Factors, Treatment Outcome, Viral Load drug effects, Anti-HIV Agents administration & dosage, Antiretroviral Therapy, Highly Active methods, HIV Infections drug therapy, HIV-1, Heterocyclic Compounds, 3-Ring administration & dosage
- Abstract
Background: A network meta-analysis can provide estimates of relative efficacy for treatments not directly studied in head-to-head randomized controlled trials. We estimated the relative efficacy and safety of dolutegravir (DTG) versus third agents currently recommended by guidelines, including ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV), cobicistat-boosted elvitegravir (EVG/c), ritonavir-boosted lopinavir (LPV/r), raltegravir (RAL), and rilpivirine (RPV), in treatment-naive HIV-1-infected patients., Methods: A systematic review of published literature was conducted to identify phase 3/4 randomized controlled clinical trials (up to August 2013) including at least one third agent of interest in combination with a backbone nucleoside reverse transcriptase inhibitor (NRTI) regimen. Bayesian fixed-effect network meta-analysis models adjusting for the type of nucleoside reverse transcriptase inhibitor backbone (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC] or abacavir/lamivudine [ABC/3TC]) were used to evaluate week 48 efficacy (HIV-RNA suppression to <50 copies/mL and change in CD4+ cells/µL) and safety (lipid changes, adverse events, and discontinuations due to adverse events) of DTG relative to all other treatments. Sensitivity analyses assessing the impact of NRTI treatment adjustment and random-effects models were performed., Results: Thirty-one studies including 17,000 patients were combined in the analysis. Adjusting for the effect of NRTI backbone, treatment with DTG resulted in significantly higher odds of virologic suppression (HIV RNA<50 copies/mL) and increase in CD4+ cells/µL versus ATV/r, DRV/r, EFV, LPV/r, and RPV. Dolutegravir had better or equivalent changes in total cholesterol, LDL, triglycerides, and lower odds of adverse events and discontinuation due to adverse events compared to all treatments. Random-effects and unadjusted models resulted in similar conclusions., Conclusion: Three clinical trials of DTG have demonstrated comparable or superior efficacy and safety to DRV, RAL, and EFV in HIV-1-infected treatment-naive patients. This network meta-analysis suggests DTG is also favorable or comparable to other commonly used third agents (ATV/r, LPV/r, RPV, and EVG/c).
- Published
- 2014
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