OBJECTIVES: E/C/F/TAF is the combination of Elvitegravir/Cobicistat/Emtricitabine with Tenofovir Alafenamide, a new prodrug of tenofovir with a better biodisponibility and safety profile than Tenofovir Disoproxil Fumarate (TDF) . We used adjusted indirect comparison to estimate the relative efficacy of E/C/F/TAF versus HAART based on raltegravir (RAL) or dolutegravir (DTG) in treatment-naïve HIV-1 infected patients that was not directly studied in head-to-head randomized controlled trials. METHODS: A systematic review of published literature was conducted to identify phase 3 randomized controlled clinical trials (up to February 2015) including at least one third agent of interest. Network adjusted indirect comparison was used to evaluate week 48 relative effectiveness (HIV-RNA suppression to 50 copies/mL) after checking for homogeneity and absence of interaction between baseline characteristics and efficacy. Analyses based on secondary networks were performed to assess validity. A ten percent margin was used for non-inferiority.  RESULTS: Twelve studies were included in the network. Baseline patient’s characteristics were slightly different between studies published before and after 2011 due to changes in 2011 in treatment initiation guidelines. No significant interactions were observed in the studies between baseline characteristics and week 48 virologic suppression. E/C/F/TAF was associated with a non-significant different rate for week 48 virologic suppression compared to DTG + ABC/3TC or RAL + TDF/FTC (Relative Risk = 0.98 (0.89 - 1.07) and 1.01 (0.92 - 1.12) respectively). Using secondary networks yielded similar results.  CONCLUSIONS: This indirect comparison suggests that with ten percent non-inferiority margin E/C/F/TAF has a similar efficacy then DTG or RAL based HAART.