Comparative Efficacy and Metabolic Safety of Dolutegravir- versus Efavirenz-Based First-Line ART in the Modern TLD Transition Era: A Systematic Review and Meta-Analysis

This review is expected to produce a comprehensive quantitative synthesis demonstrating that DTG-based first-line ART achieves superior virological suppression compared with EFV-based regimens at 48 weeks, with fewer treatment discontinuations due to adverse events and lower rates of CNS adverse events. However, DTG is expected to be associated with greater weight gain and higher rates of incident obesity, particularly in sub-Saharan African settings and among women, representing a clinically important metabolic trade-off. Mortality and mother-to-child transmission outcomes are expected to show wide confidence intervals given the rarity of events across available trials. Evidence certainty will be assessed using the GRADE framework, with Summary of Findings tables generated for each primary and key secondary outcome. The findings will directly inform clinical and programmatic decision-making around the ongoing global TLD transition, particularly for national HIV programmes in low- and middle-income countries weighing the virological benefits of DTG against its cardiometabolic safety profile. The complete dataset, R analysis scripts, and forest plots will be made publicly available via OSF upon publication.