Comparative Clinical Effectiveness of TLD versus TLE Regimens in HIV/AIDS: A Systematic Review

Antiretroviral therapy (ART) remains the cornerstone of Human Immunodeficiency Virus (HIV) management. The World Health Organization recommends Tenofovir–Lamivudine–Dolutegravir (TLD) as a preferred first-line regimen in many settings, replacing Tenofovir–Lamivudine–Efavirenz (TLE) because of its favorable virological efficacy, resistance barrier, and tolerability. However, comparative evidence across different patient populations remains heterogeneous. This systematic review aimed to compare the clinical effectiveness of TLD and TLE in patients with HIV/AIDS, focusing on virological suppression, immunological recovery, clinical outcomes, and safety. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 framework. Literature searches were conducted in PubMed, PubMed Central, ScienceDirect, and Google Scholar for studies published from January 2021 to May 2026. Eligible original studies were selected using predefined inclusion and exclusion criteria, and findings were synthesized narratively because of methodological and population heterogeneity. Of 50 records identified, 20 studies were included, covering adults, children, pregnant and lactating women, patients switching therapy, and patients with advanced AIDS. Sample sizes ranged from 102 to 2,599 participants, with follow-up periods of 6–24 months. Overall, most studies reported more favorable virological outcomes with dolutegravir-based regimens. For example, viral suppression at six months was 88.57% versus 55.71% in one adult study, while pediatric and advanced AIDS cohorts also showed higher suppression rates with DTG-based therapy. Several studies reported greater CD4+ recovery, improved clinical outcomes, better treatment durability, and fewer adverse-event-related regimen changes with TLD or DTG-based regimens. The findings indicate that TLD/DTG-based therapy is consistently associated with favorable virological and immunological outcomes compared with TLE/EFV-based therapy. Nevertheless, heterogeneity and the predominance of observational study designs limit causal interpretation. Prospective and randomized studies with longer follow-up are warranted to strengthen the evidence on long-term effectiveness and safety.