Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-week results of a randomized trial.

Barbara Rossetti,Michele Trezzi,Manuela Colafigli,Benedetta Canovari,Vincenzo Colangeli,Andrea Antinori,Maurizio Zazzi,Alessandra Fantauzzi,Silvia Lamonica,Vincenzo Vullo,Pierfrancesco Grima,Valeria Ghisetti,Stefano Rusconi,Pierluigi Navarra,Antonella D’Arminio Monforte,Simona Di Giambenedetto,Alessandro D’Avino,Daniela Francisci,Antonio Di Biagio,Maria Carla Re,Valeria Micheli,Lucia Lisi,Genny Meini,Giancarlo Orofino,Roberta Gagliardini,Francesca Vignale,Andrea De Luca,Gaetana Sterrantino,Alessandra Latini,Claudio Maria Mastroianni

doi:10.1371/journal.pone.0187393

Abstract

ObjectivesPrimary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48.MethodsPatients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).ResultsIn June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm.ConclusionSwitching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy.

Highlights

Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy
Antiretroviral therapy (ART) significantly reduces morbidity and mortality associated with HIV infection; this is best achieved by chronically maintaining undetectable levels of HIV-1 RNA in patients plasma [1]
The combination of three active agents in the first-line regimen is the standard of care to achieve this virological goal and nucleoside reverse transcriptase inhibitors (NRTIs) are the essential component of all initial treatment strategies [2,3,4]

Summary

Introduction

Antiretroviral therapy (ART) significantly reduces morbidity and mortality associated with HIV infection; this is best achieved by chronically maintaining undetectable levels of HIV-1 RNA in patients plasma [1]. The combination of three active agents in the first-line regimen is the standard of care to achieve this virological goal and nucleoside reverse transcriptase inhibitors (NRTIs) are the essential component of all initial treatment strategies [2,3,4]. The drug is approved only for patients failing previous regimens, given its inferior efficacy as initial therapy [14,15,16]. Agents with this mechanism of action should ideally be used early during treatment, before the possible switch from R5 to non-R5 tropism at later stages [17]

Objectives

Methods

Results

Conclusion