Background:Data are required regarding the feasibility of conducting a randomized trial of point-of-care viral load (VL) testing to guide management of HIV viremia and to provide estimates of effect to guide potential future trial design.Setting:Two public South African clinics during the dolutegravir-based antiretroviral therapy (ART) rollout.Methods:We randomized adults receiving first-line ART, with recent VL ≥1000 copies/mL, in a 1:1 ratio to receive point-of-care Xpert HIV-1 VL versus standard-of-care laboratory VL testing after 12 weeks. Feasibility outcomes included proportions of eligible patients enrolled and completing follow-up and VL process outcomes. Estimates of effect were assessed using the trial primary outcome of VL <50 copies/mL after 24 weeks.Results:From August 2020 to March 2022, we enrolled 80 eligible participants, an estimated 24% of those eligible. 47 of 80 (58.8%) were women, and the median age was 38.5 years (interquartile range [IQR], 33–45). 44 of 80 (55.0%) were receiving dolutegravir, and 36 of 80 (465.0%) were receiving efavirenz. After 12 weeks, point-of-care participants received VL results after median 3.1 hours (IQR 2.6–3.8), versus 7 days (IQR 6–8,P< 0.001) in standard of care. Twelve-week follow-up VL was ≥1000 copies/mL in 13 of 39 (33.3%) point-of-care participants and in 16 of 41 (39.0%) standard-of-care participants; 11 of 13 (84.6%) and 12 of 16 (75.0%) switched to second-line ART. After 24 weeks, 76 of 80 (95.0%) completed follow-up. 27 of 39 (69.2% [95% CI: 53.4 to 81.4]) point-of-care participants achieved VL <50 copies/mL versus 29 of 40 (72.5% [57.0 to 83.9]) standard-of-care participants. Point-of-care participants had median 3 (IQR, 3–4) clinical visits versus 4 (IQR, 4–5) in standard-of-care participants (P< 0.001).Conclusions:It was feasible to conduct a trial of point-of-care VL testing to manage viremia. Point-of-care VL lead to quicker results and fewer clinical visits, but estimates of 24-week VL suppression were similar between arms.Trial Registration:Pan African Clinical Trials Registry: PACTR202001785886049.