Persistence on dolutegravir-containing two- and three-drug-regimens in clinical practice

Abstract

Background: Drug-sparing antiretroviral treatment (ART) regimens are gaining interest in the treatment of HIV-1. Dolutegravir (DTG), a second-generation integrase inhibitor, has been pivotal in this development, allowing treatment with fewer drugs while maintaining virologic control. This study aimed to analyze and compare treatment persistence in people with HIV (PWH) on DTG-based two-drug regimens (2DRs) and three-drug regimens (3DRs) at an HIV center in Munich, Germany. Methods: Retrospective, observational, longitudinal analysis using electronic patient records at MVZ M & uuml;nchen am Goetheplatz. All people with HIV-1 receiving DTG-containing ART regimens-combined with rilpivirine (RPV) or lamivudine (3TC) for 2DRs, or with tenofovir (TAF or TDF) and emtricitabine (FTC), or abacavir (ABC) and FTC for 3DRs-were included. Exclusion criteria included HIV-2 infection or concomitant use of other antiretroviral drugs. The primary endpoint was the comparison of time-to-discontinuation between 2DRs and 3DRs. Secondary endpoints included an analysis of reasons for discontinuation. Kaplan-Meier estimates, log-rank tests, and accelerated failure time (AFT) models were used for statistical analysis. Results: Overall, 854 individuals were included in the study, with 462 (54.1%) on a 2DR. For the primary endpoint, 141 events occurred. In the unadjusted analysis, treatment persistence was significantly longer in the 2DR group compared to the 3DR group (p = .005, log-rank test). Median persistence was not reached in either group. In AFT models, being on a 2DR was associated with a 74.9% (23.0%-126.8%), 85.7% (30.5%-140.8%), and 98.0% (36.7%-159.0%) longer time-to-discontinuation in the unadjusted, partially adjusted (sex, age, route of transmission), and fully adjusted models (additionally adjusted for CD4 nadir and baseline resistance) after multiple imputation, respectively. For the secondary endpoint, 196 events occurred. Persistence on 2DRs and 3DRs was found to be comparable (p = .190). Reasons for discontinuation included cardiovascular risk, unspecified side effects, gastrointestinal side effects, impaired kidney function, weight gain, convenience (switch to a single-tablet regimen), and other factors. Weight gain (p = .018), impaired renal function (p = .008), cardiovascular risk (p = .004), unspecified side effects (p = .003), gastrointestinal side effects (p = .003), and switching to a single-tablet regimen (p < .001) remained significant after adjusting for multiple testing. Conclusions: This study found significant associations between the type of antiretroviral treatment regimen (2DR or 3DR) and time-to-discontinuation. DTG-based 2DRs were associated with significantly longer treatment persistence compared to 3DRs, as confirmed in parametric and non-parametric time-to-event analyses and after adjusting for baseline differences. Virologic efficacy was comparable between the two regimens, aligning with previous studies. The main drivers of higher discontinuation rates in 3DRs were side effects, supporting the hypothesis that drug-sparing regimens might contribute to better tolerability and lower toxicity. These findings suggest that drug-sparing regimens could lead to improved long-term treatment adherence. However, the study's retrospective nature and center-specific characteristics may limit generalizability. More real-world data are warranted to confirm these results.