PMID- 27617024 OWN - NLM STAT- MEDLINE DCOM- 20170615 LR - 20201209 IS - 1742-6405 (Electronic) IS - 1742-6405 (Linking) VI - 13 IP - 1 DP - 2016 TI - Dolutegravir(DTG, S/GSK1349572) combined with other ARTs is superior to RAL- or EFV-based regimens for treatment of HIV-1 infection: a meta-analysis of randomized controlled trials. PG - 30 LID - 10.1186/s12981-016-0115-x [doi] LID - 30 AB - BACKGROUND: The first-generation integrase inhibitors (INIs) raltegravir (RAL) and elvitegravir (EVG) have shown efficacy against HIV infection, but they have the limitations of once-more daily dosing and extensive cross-resistance. Dolutegravir (DTG, S/GSK1349572), a second-generation drug that overcomes such shortcomings, is under spotlight. The purpose of this study is to review the evidence for DTG use in clinical settings, including its efficacy and safety. METHODS: PubMed, EMbase, Ovid, Web of Science, Science Direct, and related websites were screened from establishment until July 2013, and scientific meeting proceedings were manually searched. Two reviewers independently screened 118 citations repeatedly to identify randomized controlled trials comparing the efficacy and safety of DTG-based regimen with those of RAL- or elvitegravir-based regimens. Using the selected studies with comparable outcome measures and indications, we performed a meta-analysis based on modified intention-to-treat (mITT), on-treatment (OT), and as-treated (AT) virological outcome data. Independent data extraction and quality assessment were conducted. RESULTS: Four unique studies were included with the use of DTG in antiretroviral therapy-naive patients. In therapy-naive patients, DTG combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) resulted in a significantly better virological outcome with a mITT relative risk (RR)of 1.07 (95 % confidence interval (95 % CI 1.03-1.12). Evidence further supported use of DTG had a better virological suppression in the 50 mg once daily group (mITT RR 1.07; 95 % CI 1.03-1.12) as well as in the sub-analysis in dolutegravir/efavirenz(DTG/EFV) and dolutegravir/raltegravir (DTG/RAL) groups (RR 1.09, 95 % CI 1.03-1.15; RR 1.06, 95 % CI 0.98-1.15, respectively). In the matter of safety of DTG-based regimen, the risk of any event was RR 0.98 (95 % CI 0.94-1.01), the risk of serious adverse events (AEs) was RR 0.84 (95 % CI 0.62-1.15), and the risk of drug-related serious AEs was RR 0.33 (95 % CI 0.13-0.79). CONCLUSION: In general, DTG 50 mg given once daily combined with an active background drug is a better choice in terms of both efficacy and safety. FAU - Jiang, Junjun AU - Jiang J AD - Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, 530021 Guangxi China. FAU - Xu, Xi AU - Xu X AD - Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, 530021 Guangxi China. FAU - Guo, Wenqin AU - Guo W AD - Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, 530021 Guangxi China. FAU - Su, Jinming AU - Su J AD - Guangxi Center for Disease Control and Prevention, Nanning, 530028 Guangxi China. FAU - Huang, Jiegang AU - Huang J AD - Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, 530021 Guangxi China. FAU - Liang, Bingyu AU - Liang B AD - Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, 530021 Guangxi China. FAU - Chen, Hui AU - Chen H AD - Geriatrics Digestion Department of Internal Medicine, The First Affiliated Hospital of GuangXi Medical University, Nanning, 530021 Guangxi China. FAU - Zang, Ning AU - Zang N AD - Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, 530021 Guangxi China. AD - Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning, 530021 Guangxi China. FAU - Liao, Yanyan AU - Liao Y AD - Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, 530021 Guangxi China. AD - Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning, 530021 Guangxi China. FAU - Ye, Li AU - Ye L AD - Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, 530021 Guangxi China. FAU - Liang, Hao AU - Liang H AD - Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, 530021 Guangxi China. AD - Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning, 530021 Guangxi China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review DEP - 20160908 PL - England TA - AIDS Res Ther JT - AIDS research and therapy JID - 101237921 RN - 0 (Alkynes) RN - 0 (Anti-HIV Agents) RN - 0 (Benzoxazines) RN - 0 (Cyclopropanes) RN - 0 (Dideoxynucleosides) RN - 0 (Drug Combinations) RN - 0 (Heterocyclic Compounds, 3-Ring) RN - 0 (Oxazines) RN - 0 (Piperazines) RN - 0 (Pyridones) RN - 0 (abacavir, lamivudine drug combination) RN - 0W860991D6 (Deoxycytidine) RN - 2T8Q726O95 (Lamivudine) RN - 43Y000U234 (Raltegravir Potassium) RN - 99YXE507IL (Tenofovir) RN - DKO1W9H7M1 (dolutegravir) RN - JE6H2O27P8 (efavirenz) SB - IM MH - Alkynes MH - Anti-HIV Agents/*administration & dosage MH - Benzoxazines/*administration & dosage MH - Cyclopropanes MH - Deoxycytidine/administration & dosage MH - Dideoxynucleosides/administration & dosage MH - Drug Combinations MH - HIV Infections/*drug therapy/virology MH - HIV-1/*isolation & purification MH - Heterocyclic Compounds, 3-Ring/*administration & dosage MH - Humans MH - Lamivudine/administration & dosage MH - Oxazines MH - Piperazines MH - Pyridones MH - Raltegravir Potassium/*administration & dosage MH - Randomized Controlled Trials as Topic MH - Tenofovir/administration & dosage MH - Treatment Outcome PMC - PMC5016965 OTO - NOTNLM OT - DTG OT - Efficacy OT - HIV/AIDS OT - Meta-analysis OT - Safety EDAT- 2016/09/13 06:00 MHDA- 2017/06/16 06:00 PMCR- 2016/09/08 CRDT- 2016/09/13 06:00 PHST- 2016/06/29 00:00 [received] PHST- 2016/08/30 00:00 [accepted] PHST- 2016/09/13 06:00 [entrez] PHST- 2016/09/13 06:00 [pubmed] PHST- 2017/06/16 06:00 [medline] PHST- 2016/09/08 00:00 [pmc-release] AID - 115 [pii] AID - 10.1186/s12981-016-0115-x [doi] PST - epublish SO - AIDS Res Ther. 2016 Sep 8;13(1):30. doi: 10.1186/s12981-016-0115-x. eCollection 2016.