Journal Article

Durability and effectiveness of dual vs. triple therapy and tablet simplification in ART: findings from the Italian MOSAICO study

Gregori, Dario, Agnoletto, Laura, Silvani, Maria Chiara, Mengato, Daniele, Berti, Giacomo, Francavilla, Andrea, Chiumente, Marco, Michielan, Silvia, Mazzitelli, Maria, Venturini, Francesca, Cattelan, Anna Maria, Cappellazzo, Linda

2025

Overview

Treatment optimization in people with HIV (PWH) has increasingly focused on reducing drug burden and improving regimen simplicity. However, comparative real-world evidence on dual therapy (DT) vs. triple therapy (TT), and single-tablet regimens (STR) vs. multi-tablet regimens (MTR), remains limited. The MOSAICO study is a multicenter, retrospective observational analysis conducted across 20 centers, including people with HIV on a stable virological suppression who switched antiretroviral therapy between 2017 and 2019. People were followed-up up to 48 months post-switch. Comparative analyses assessed virological suppression (HIV-RNA <50 copies/mL), CD4 T cell count, CD4/CD8 ratio, and treatment discontinuation. Propensity score weighting was applied to adjust for baseline differences. Four hundred ninety-one PWH were included. Both DT and triple therapy groups maintained high levels of virological suppression over 48 months (12 months: 97.1% vs. 91.6%; 24 months: 100% vs. 95.6%; 36 months: 100% vs. 96.9%; 48 months: 100% vs. 100%). From 24 months onward, all persons living with HIV remaining on their respective regimens achieved full virological suppression. Immunological recovery (CD4 count and CD4/CD8 ratio) was comparable across groups, although TT and MTR groups showed greater increases from lower baselines. STRs demonstrated significantly greater treatment durability than MTRs (aHR = 0.56, 95% CI: 0.32-0.97; p = 0.039), while no significant difference in persistence was found between DT and TT. INSTI-based regimens were predominant in DT and MTR arms (DT vs. TT: 84% vs. 46.52%, p < 0.01; MTR vs. STR: 59.38% vs. 47.14%, p < 0.01). The real-world effectiveness of both dual and triple therapies when tailored to appropriate person profiles. STRs offer enhanced long-term persistence compared to MTRs, supporting treatment simplification strategies. These results reinforce the importance of individualized treatment approaches balancing clinical effectiveness with person-centered considerations such as pill burden and tolerability. Limitations include the retrospective design and the lack of quality-of-life data, which may affect interpretation of patient-centered outcomes. Future efforts should expand access to dual-agent STR to further improve Antiretroviral Therapy outcomes.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Antiretroviral drugs / Antiretroviral therapy / CD4 antigen / CD8 antigen / Clinical medicine / Comparative analysis / Drug resistance / dual therapy / HIV / HIV treatment / Human immunodeficiency virus / Immunology / Inclusion / Infectious diseases / Life expectancy / Lymphocytes T / Optimization / people with HIV / Pharmacology / Quality of life / Regression analysis / Regulatory approval / Short tandem repeats / single tablet regimen / switch therapy / Toxicity