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

Abstract

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 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.

Results: 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).

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 Antiretroviral Therapy outcomes.

Keywords: HIV treatment; dual therapy; optimization; people with HIV; single tablet regimen; switch therapy.

FIGURE 1

Sankey diagram of combination therapies that have at least 20 PWH at the first switch. Maximum 5 switch were recorded in follow up. NA bar represents PWH who have no longer switched.

FIGURE 2

Description of the comparisons between DT vs. TT and MTR vs. STR through efficacy endpoints registered at baseline, 12-, 24-, 36- and 48-month post-switch. CD4⁺ counts cells/mL and CD4/CD8 ratio are represented through median and IQR. Number of persons living with HIV with viral load <50 copies/mL are represented through percentage.

FIGURE 3

(a) Kaplan–Meier curves for time to treatment discontinuation: DT vs. TT (24-month follow-up). (b) Kaplan–Meier curves for time to treatment discontinuation: MTR vs. STR (24-month follow-up).