Dolutegravir Plus Two Nucleoside Reverse Transcriptase Inhibitors versus Efavirenz Plus Two Nucleoside Reverse Transcriptase Inhibitors As Initial Antiretroviral Therapy for People with HIV: A Systematic Review
Background Dolutegravir (DTG) is a once daily unboosted second generation integrase inhibitor that along with two nucleoside reverse transcriptase inhibitors is one of several regimens recommended by the United States, United Kingdom and European Union for first line antiretroviral treatment of people with HIV infection. Our objective was to review the evidence for the efficacy and safety of DTG based first line regimens compared to efavirenz (EFV) based regimens. Methods We conducted a systematic review. We comprehensively searched a range of databases as well as conference abstracts and a trials registry. We used Cochrane methods in screening and data collection and assessed each study's risk of bias with the Cochrane tool. We meta analyzed data using a fixed effects model. We used GRADE to assess evidence quality. Results From 492 search results, we identified two randomized controlled trials, reported in five peer reviewed articles and one conference abstract. One trial tested two DTG based regimens (DTG abacavir (ABC) lamivudine (3TC) or DTG tenofovir emtricitabine) against an EFV based regimen (EFV+ ABC+3TC) The other trial tested DTG+ABC+3TC against EFV+ABC+3TC. In meta analysis, DTG containing regimens were superior to EFV containing regimens at 48 weeks and at 96 weeks (RR 1.10, 95% CI 1.04 1.16; and RR 1.12, 95% CI 1.04 1.21, respectively) In one trial, the DTG containing regimen was superior at 144 weeks (RR 1.13, 95% CI 1.02 1.24) DTG containing regimens were superior in reducing treatment discontinuation compared to those containing EFV at 96 weeks and at 144 weeks (RR 0.27, 95% CI 0.15 0.50; and RR 0.28, 95% CI 0.16 0.48, respectively) Risk of serious adverse events was similar in each regimen at 96 weeks (RR 1.15, 95% CI 0.80 1.63) and 144 weeks (RR 0.93, 95% CI 0.68 1.29) Risk of bias was moderate overall, as was GRADE evidence quality. Conclusions DTG based regimens should be considered in future World Health Organization guidelines for initial HIV treatment.
PloS one