Objectives: To evaluate the plasma trough concentrations ( C trough ) of dolutegravir and rilpivirine used in combination with simeprevir and sofosbuvir in HIV/hepatitis C virus (HCV)-coinfected patients with liver cirrhosis. Virological efficacy and safety of both ART and anti-HCV therapy were assessed. Patients and methods: A prospective observational study in HIV/HCV-coinfected patients with liver cirrhosis on ART with dolutegravir plus rilpivirine and treated with simeprevir plus sofosbuvir (±ribavirin) was conducted. Dolutegravir, rilpivirine, GS-331007 (sofosbuvir metabolite) and simeprevir C trough were evaluated with a validated HPLC method at anti-HCV treatment baseline and weeks 2 and 4. Geometric means were calculated to summarize C trough values. Results: Twelve patients were evaluated: 75% were males and the median (IQR) age was 53 (53-55) years. All patients were Child-Pugh stage A, except one who was stage B. The geometric mean (95% CI) of C trough of rilpivirine and dolutegravir did not change between baseline and week 4 ( P = 0.654 and P = 0.268, respectively), with corresponding overall values of 135 (102-177) and 1357 (970-1897) ng/mL. The overall geometric mean (95% CI) of GS-331007 and simeprevir C trough was 370 (268-512) and 2537 (1569-4101) ng/mL, respectively, without significant variation between weeks 2 and 4 ( P = 0.643 and P = 0.179, respectively). All patients completed anti-HCV treatment, achieving sustained virological response. All but two patients maintained undetectable HIV-RNA up to post-treatment week 24. Conclusions: Dolutegravir and rilpivirine C trough appeared not to be affected by concomitant treatment with simeprevir plus sofosbuvir in these HIV/HCV-coinfected patients with liver cirrhosis, supporting the use of this antiretroviral regimen in this setting.