Durability and Effectiveness of Dual vs Triple Therapy and Tablet Simplification in ART: Findings from the Italian MOSAICO Study

Daniele Mengato^1*Giacomo Berti²Andrea Francavilla²Silvia Michielan³Linda Cappellazzo⁴Laura Agnoletto⁵Maria Chiara Silvani⁶Marco Chiumente⁷Dario Gregori²Maria Mazzitelli¹Francesca Venturini¹ANNA MARIA CATTELAN²

• ¹Azienda Ospedale Universita Padova, Padua, Italy
• ²Universita degli Studi di Padova Unita di Biostatistica Epidemiologia e Salute Pubblica, Padua, Italy
• ³Azienda AUSL of Modena, Modena, Italy
• ⁴Ospedale di Bolzano, Bolzano, Italy
• ⁵Azienda Ulss 5 Polesana, Rovigo, Italy
• ⁶Azienda USL Romagna, Ravenna, Italy
• ⁷Italian society of clinical pharmacy and therapeutics (SIFaCT), Turin, Italy

Introduction: 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.Methods: The MOSAICO study is a multicenter, retrospective observational analysis conducted across 20 centers, including PWH 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.Results: 419 PWH were included. Both DT and TT 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 patients 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).Discussion: 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 ART outcomes.