Non-inferiority of simplified dolutegravir monotherapy compared to continued combination antiretroviral therapy that was initiated during primary HIV infection: a randomized, controlled, multi-site, open-label, non-inferiority trial

Abstract

Background Patients who start combination antiretroviral therapy (cART) during primary HIV-1 infection show a smaller HIV-1 latent reservoir, less immune activation and a smaller viral diversity compared to patients who start cART during chronic infection. We conducted a pilot study to test whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir monotherapy. Methods EARLY-SIMPLIFIED is a randomized, open label, non-inferiority trial. Patients who started cART <180 days after estimated date of a documented primary HIV-1 infection and had a HIV-1 RNA <50 copies/mL plasma for at least 48 weeks were randomized (2:1) to monotherapy with dolutegravir 50 mg once-daily or to continuation of cART. The primary efficacy endpoint was the proportion of patients with <50 HIV-1 RNA copies/mL on or before week 48; non-inferiority margin 10%. Results Of the 101 patients randomized, 68 were assigned to simplification to dolutegravir monotherapy and 33 to continuation of cART. At week 48 in the per-protocol population, 67/67 (100%) had virological response in the dolutegravir monotherapy group versus 32/32 (100%) in the cART group (difference 0.00%, 95%-CI [-100%, 4.76%]). This showed non-inferiority of the dolutegravir monotherapy at the pre-specified level. Conclusion In this pilot study consisting of patients who initiated cART <180 days after the estimated day of a documented primary HIV-1 infection and had <50 HIV-1 RNA copies/mL for at least 48 weeks, monotherapy with once-daily dolutegravir was non-inferior to cART. Our results suggest that future simplification studies should use a stratification according to time of HIV infection and start of first cART.