Effectiveness and tolerance of single tablet versus once daily multiple tablet regimens as first-line antiretroviral therapy - Results from a large french multicenter cohort study.

Laurent Cotte,Clotilde Allavena,Marc-Antoine Valantin,Tristan Ferry,Jean-Jacques Parienti,David Rey,Pascal Pugliese,Isabelle Poizot-Martin,Claudine Duvivier,André Cabié,Pierre Pradat,Dat’aids Study Group ,Antoine Cheret,Pierre Dellamonica

doi:10.1371/journal.pone.0170661

Abstract

ObjectivesPill burden during antiretroviral treatment (ART) is associated with worse adherence and impaired virological suppression. We compared the effectiveness, tolerance, and persistence on treatment of single tablet regimens (STRs) with non-STR once-daily regimens in patients receiving first-line ART.MethodsRetrospective analysis of naïve HIV-1 infected patients prospectively enrolled in the French Dat’AIDS cohort and initiating first-line ART with STRs or once-daily non-STRs from 2004 to 2013. The primary outcome was time to treatment discontinuation defined by any change in the treatment regimen. STR and non-STR groups were compared controlling for baseline risk factors by inverse probability weighted treatment Cox analysis (IPWT) and propensity-score matching (PSM).ResultsOverall, 3212 patients (STR 499, non-STR 2713) were included. Median time to treatment discontinuation was shorter in non-STR patients than in STR patients, both in the IPWT (HR = 0.61, p<0.0001) and the PSM cohort (HR = 0.55, p<0.0001). This difference disappeared when censoring ART modification for simplification, both in the IPWT (HR = 0.97, p = 0.65) and the PSM cohort (HR = 0.91, p = 0.33). A lower rate of virological failure was observed with STRs than with non-STRs in both cohorts (HR = 0.23; p = 0.002 and HR = 0.22, p = 0.003, respectively). A lower rate of treatment modification for adverse event was observed with non-STRs in the IPWT cohort (HR = 1.46, p<0.0001), but not in the PSM cohort (HR = 1.22, p = 0.11).ConclusionFirst-line therapy with STRs was associated with a longer time to treatment discontinuation than with non-STRs. However, when ART modification for simplification was not considered as a failure, STRs and non-STRs were similar.

Highlights

During the past decades, HIV combined antiretroviral therapy (ART) has drastically evolved with as a consequence a better control of HIV infection and a reduction of HIV-related morbidity and mortality
Median time to treatment discontinuation was shorter in non-single tablet regimens (STRs) patients than in STR patients, both in the inverse probability weighted treatment Cox analysis (IPWT) (HR = 0.61, p
A lower rate of virological failure was observed with STRs than with non-STRs in both cohorts (HR = 0.23; p = 0.002 and hazard ratio (HR) = 0.22, p = 0.003, respectively)

Summary

Introduction

HIV combined antiretroviral therapy (ART) has drastically evolved with as a consequence a better control of HIV infection and a reduction of HIV-related morbidity and mortality. Adherence to treatment has been reported as a key factor for ART success and international guidelines underscore the importance of simplifying regimens to improve adherence [1]. Treatment simplification first became possible with the development of drugs with longer half-lives allowing once-daily dosing. Adherence to these once-daily regimens was shown to be significantly better than with 3-times and 4-times-daily regimens [2]. Compared with multiple tablet regimens, some STRs have been associated with better adherence [10,11,12,13,14,15], and improved quality of life (QoL) [15,16]. Some authors described the different factors to be considered for the choice of a particular STR and stressed the need for careful clinical, virological and immunological monitoring along with regular adherence assessment to achieve treatment success [18]

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