| Background and Objective: Initiation of antiretroviral therapy(ART)in HIV-infected individuals typically consists of two nucleoside reverse transcriptase inhibitors combined with a third core drug,which can be either a non-nucleoside reverse transcriptase inhibitor or an enhanced protease inhibitor(PI)or an integrase inhibitor(INI).Doravirine(DOR)is the latest non-nucleoside reverse transcriptase inhibitor.DOR+ tenofovir fumarate(TDF)+lamivudine(3TC)/emtricitabine(FTC)was compared with EFV or DRV-based ART in treatment-naive HIV-1 patients in two phase 3 randomized controlled trials(RCTs),and showed good antiviral activity,safety and tolerability.However,DOR+TDF+3TC/FTC has not conducted direct head-to-head RCT with all first-line ARTs.The purpose of this study was to compare the 48-week efficacy and safety of DOR+TDF+3TC/FTC with other traditional three-drug ARTs in treatment-naive adults with HIV-1 in a Bayesian network meta-analysis.Methods: A search strategy was developed for systematically searching phase 3 and 4RCTs for treatment-naive HIV-1 adults from Pub Med,Embase,Web of Science and Cochrane Library databases.Relevant systematic reviews,meta-analyses and their references were also reviewed.Papers were screened and data extracted according to inclusion and exclusion criteria.The quality of each included trial was assessed using the Cochrane risk of bias tool.R software and GEMTC package were used to conduct the network meta-analysis in a Bayesian framework.The results were calculated via Markov chain Monte Carlo methods and convergence was evaluated using the potential scale reduction factor.By comparing the size of the deviance information criterion of the fixed effect model and the random effect model,a more suitable model was selected.The consistency test was analyzed by node splitting method,and P<0.05 indicated the existence of inconsistency,which tended to use random effect model.The statistical results were presented by odds ratio(OR),mean and corresponding 95% credible interval(Cr I).The cumulative area under the ranking curve(SUCRA)value of each regimen was calculated to evaluate the ranking among multiple regimens in this paper.CINe MA was used to grade the quality of evidence.Results: A total of 7298 citations were obtained,and 39 articles met the inclusion criteria,involving 39 randomized controlled trials,and a total of 21110 participants.As for virological suppression(VS),the forest plot showed that DOR+TDF+3TC/FTC had a higher proportion of patients achieving VS compared with most NNRTI and PI-based regimens,showing good efficacy.However,the SUCRA value of DOR+TDF+3TC/FTC(61.51%)ranked 12 th,while DTG+ tenofovir alafenamide(TAF)+FTC was the highest(90.28%),which might be the best treatment in terms of VS.In a subgroup analysis of patients with baseline viral load more than 100,000 copies/m L,in terms of VS,95% Cr I of all results included 1 and the SUCRA ranking was not high.For adverse events(AE),the incidence of DOR+TDF+3TC/FTC was lower than that of EFV+TDF+3TC/FTC and was statistically significant(OR=2.05,95%Cr I 1.05～4.01).DOR-based regimen was not statistically significant compared with most other ART,but most of the OR values were >1.In terms of serious AE,there was statistical difference between DOR+TDF+3TC/FTC and either EFV+ abacavir(ABC)+3TC(OR=3.55,95%Cr I 1.33～9.85),nevirapine+TDF+3TC/FTC(OR=3.04,95%Cr I 1.16～8.19),atazanavir/ritonavir +TDF+3TC/FTC(OR=2.51,95%Cr I 1.12～5.81),Elvitegravir/cobicistat(EVG/c)+TDF+3TC/FTC(OR=2.37,95%Cr I 1.06～5.49),EVG/c+TAF+FTC(OR=2.72,95%Cr I 1.12～6.75).As for drug-related adverse events,the OR values between DOR+TDF+3TC/FTC and EFV-based regimens were more than 1,and were statistically significant.Compared DOR-based regimen with regimens containing INI,only EVG/c+TDF+3TC/FTC had statistical significance and OR>1.Among the three outcome events of AE,serious AE and drugrelated AE,the SUCRA values of DOR+TDF+3TC/FTC were 74.55%,83.72% and 84.26%,respectively,all ranking third,and showing good safety.In terms of blood lipids,DOR+TDF+3TC/FTC performed well,and the forest plot showed that regimen with the greatest difference from DOR+TDF+3TC/FTC was lopinavir/ritonavir + zidovudine(AZT)+3TC in triglyceride,EFV+AZT+3TC in total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol.The SUCRA values of DOR+TDF+3TC/FTC were 91.12%,91.34%,70.18% and 81.18% in total cholesterol,triglyceride,low-density lipoprotein cholesterol and high-density lipoprotein cholesterol,respectively.All comparative results were graded by the CINe Ma,and most of the results were rated as "moderate" or "low" in the four grades of "high","medium","low" and "very low ".Conclusion: In the absence of a direct comparison between DOR+TDF+3TC/FTC and conventional three-drug regimens,this study provides information on the efficacy and safety of these regimens in treatment-naive HIV-1 infected adults.The good efficacy and safety of DOR+TDF+3TC/FTC in treatment-naive HIV-1 infected adults support the use of this regimen. |
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