OBJECTIVES: There is a growing call for the use of endonodal trials within network meta-analyses (NMA), such as for informative priors or improved connectivity. Endonodal trials can also be used to further inform arm-specific meta-regression coefficients, which may be used to simplify node definitions in combination therapy. We applied this concept to a network of first line antiretroviral therapy (ART) to determine if efavirenz (EFV) still belongs in the preferred regimen. METHODS: We conducted a systematic search of electronic databases up to March 1, 2015. Nodes were defined as specific antivirals rather than ART regimens, which simplified interpretation of modeling and results. Backbone regimens were categorized and arm-specific meta-regression used to adjust estimates accordingly. The alternative approach was to simply reduce the evidence base to trials that did not differ with respect to backbones. The most notable trial to differ in backbones was the SINGLE trial comparing EFV to dolutegravir (DTG), central to the research question.  RESULTS: A total of 71 trials with 35,270 randomized patients informed the evidence base. DTG was found to be superior with respect to viral suppression at all time points (odds ratio [OR]: 1.87 at 48 weeks; 95% credible interval [CrI]: 1.34 – 2.64). Both DTG (OR: 0.26; 95% CrI: 0.15, 0.44) and low-dose EFV (OR: 0.39; 95% CrI: 0.17, 0.83) tended to be protective of discontinuations due to adverse events relative to standard dose EFV. Use of arm-specific regression supplemented by endonodal trials led to tighter confidence intervals facilitating decision-making. Specifically, DTG was consequently superior to EFV with respect to CD4 cell counts and raltegravir was distinguishable from EFV when it was not otherwise. CONCLUSIONS: Making full use of available evidence is the focal strength of NMA methodology. Therefore, we recommend use of endonodal trials to further supplement evidence bases requiring arm-specific meta-regression.