Background <p>Dolutegravir (DTG) is endorsed as a preferred option for both first- and second-line antiretroviral therapy (ART); however, comprehensive high-quality evidence regarding its virological effectiveness is still limited. This review evaluates and compares virological outcomes of DTG-based regimens with other ART options among people living with HIV.</p> Methods <p>A comprehensive literature search was performed in PubMed/MEDLINE, the Cochrane Library, and Google Scholar. Randomized controlled trials (RCT) comparing DTG with other antiretroviral therapy regimens and reporting virological outcomes at 48 and/or 96 weeks were included. Study quality was evaluated using the Risk of Bias 2 tool. Fixed and random effects models were applied to calculate pooled proportions and risk differences (RD) with 95% confidence intervals, with a statistical significance defined as <i>p</i> &lt; 0.05.</p> Results <p>A total of 15 RCTs including 8,360 participants were analyzed. In treatment-naïve adult individuals, DTG-based ART achieved significantly higher viral suppression than comparator ART at week 48 (RD; 0.03(95% CI 0.00, 0.05), <i>P</i> = 0.02 and week 96 (RD; 0.037(95% CI:0.012, 0.062). <i>P</i> &lt; 0.001. In treatment-experienced adult individuals with suppressed baseline viral load, switching to DTG/lamivudine maintained virological suppression without increased risk of failure (RD; 0.00(95% CI: −0.03, 0.04), <i>P</i> = 0.9. Dolutegravir efficacy was consistent across baseline viral load and CD4 subgroups but superior to low-dose efavirenz-based ART (RD; 0.06(95%CI;0.01,0.11), <i>P</i> = 0.02.</p> Conclusions <p>Dolutegravir-based ART provide superior viral suppression in treatment-naïve and maintain durable suppression in treatment-experienced adult individuals including those switching to DTG/lamivudine. These findings support DTG as a preferred first-line therapy and an effective option for regimen simplification.</p> Clinical trial number <p>Not applicable.</p>