<b>Background:</b> It has been hypothesised that <i>Schistosoma</i> co-infection exacerbates HIV progression, and hence anthelminthic intervention in co-infected individuals will delay it. We evaluated effects of high-intensity versus low-intensity praziquantel treatment of schistosomiasis on HIV disease progression among co-infected patients from fishing populations around Lake Victoria, Uganda. <b>Methods</b> : Between August 2012 and September 2015, we conducted an open-label randomised, controlled trial. Adults, antiretroviral therapy-naïve, CD4 counts ≥350 cells/μl, HIV and <i>S. mansoni</i> co-infected, were randomised 1:1 to praziquantel (40mg/kg) given quarterly (starting at enrolment) or annually (starting 12 weeks after enrolment; such that low-intensity participants were still untreated when sampled at 12 weeks). A non-randomised HIV-positive <i>S. mansoni-</i> negative comparison group was recruited. The primary outcome was mean change in plasma viral load at 12 and 60 weeks. <b>Results:</b> In total 363 participants (high-intensity 113, low-intensity 113, comparison group 137) were recruited; 96 (85.0%), 97 (85.8%) and 107 (78.1%) completed 60 weeks of follow up, respectively. Adjusting for baseline age and viral load, the geometric mean ratio (aGMR [95%CI]) viral load for high-intensity vs low-intensity groups at 12 weeks was 0.90 [0.65, 1.25] p=0.55 and at 60 weeks 1.88 [0.78, 4.53] p=0.16. Results in the comparison group were similar to trial arms. High-intensity, compared to low-intensity, treatment resulted in substantially lower <i>S. mansoni</i> prevalence at all follow up visits (p<0.05). <b>Conclusions:</b> In communities with a high burden of both <i>S. mansoni</i> and HIV infection, high-intensity treatment of <i>S. mansoni</i> does not delay HIV progression despite relevant benefit for parasite clearance. <b>Trial registration:</b> ISRCTN15371662 (17/11/2016).