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Randomized Controlled Trial
. 2017 Nov 21;12(11):e0187393.
doi: 10.1371/journal.pone.0187393. eCollection 2017.

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  1   2 , Roberta Gagliardini  2 , Genny Meini  3 , Gaetana Sterrantino  4 , Vincenzo Colangeli  5 , Maria Carla Re  6 , Alessandra Latini  7 , Manuela Colafigli  7 , Francesca Vignale  8 , Stefano Rusconi  9 , Valeria Micheli  10 , Antonio Di Biagio  11 , Giancarlo Orofino  12 , Valeria Ghisetti  13 , Alessandra Fantauzzi  14 , Vincenzo Vullo  15 , Pierfrancesco Grima  16 , Daniela Francisci  17 , Claudio Mastroianni  18 , Andrea Antinori  19 , Michele Trezzi  20 , Lucia Lisi  21 , Pierluigi Navarra  21 , Benedetta Canovari  22 , Antonella D'Arminio Monforte  23 , Silvia Lamonica  2 , Alessandro D'Avino  2 , Maurizio Zazzi  3 , Simona Di Giambenedetto  2 , Andrea De Luca  1   3 ; for GUSTA trial study group
Affiliations
Randomized Controlled Trial

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 et al. PLoS One. .

Abstract

Objectives: Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48.

Methods: Patients 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).

Results: In 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.

Conclusion: Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy.

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Conflict of interest statement

Competing Interests: ADL reports consulting fees from Gilead Sciences, Abbvie, Janssen, Bristol-Myers Squibb, ViiV Healthcare Italy, Merck Sharp and Dohme, outside the submitted work. SDG reports consulting fees from Bristol-Myers Squibb, Janssen Cilag, ViiV Healthcare Italy, Gilead, Merck Sharp and Dohme, outside the submitted work. BR reports non-financial support from Janssen, ViiV Healthcare Italy, Abbvie, Gilead, and consulting fees from Merck Sharp and Dohme, outside the submitted work. AA reports grants, consulting fees and non-financial support from Gilead Sciences, Bristol-Myers Squibb, ViiV Healthcare Italy, grants and consulting fees from Janssen Cilag, consulting fees and non-financial support from Abbvie, consulting fees from Merck, outside the submitted work. ADM reports grants and consulting fees from Bristol-Myers Squibb, Merck Sharp and Dohme Gilead, consulting fees from ViiV Healthcare Italy, outside the submitted work. CM reports consulting fees and non-financial support from ABBVIE, consulting fees from Merck Sharp and Dohme, Gilead Sciences, ViiV Healthcare Italy, BMS, non-financial support from ASTELLAS, outside the submitted work. FV reports non-financial support from Bristol-Myers Squibb, ViiV Healthcare Italy, Gilead Sciences, consulting fees from Merck Sharp and Dohme, BMS, outside the submitted work. MC reports consulting fees from Gilead Sciences, Janssen-Cilag, Merck Sharp and Dohme, Bristol-Myers Squibb, ViiV Healthcare Italy, outside the submitted work. MZ reports grants and consulting fees from ViiV Healthcare Italy, Janssen-Cilag, Gilead Sciences, outside the submitted work. SR reports grants and consulting fees from ViiV Healthcare Italy, Bristol-Myers Squibb, Merck Sharp and Dohme, Gilead Sciences, Janssen, outside the submitted work. All other authors have nothing to disclose.

Figures

Fig 1
Fig 1. GUSTA flow diagram.
Fig 2
Fig 2. Proportion of individuals without treatment failure over the 48 study weeks by randomization arm in the (a) per protocol population and (b) intention to treat population.
Arm S = study arm (switch to maraviroc + darunavir/ritonavir); Arm C = continuation arm (continuation of previous 3-drug therapy).
Fig 3
Fig 3. Proportion of individuals with virological failure over the complete follow-up available until the time of study interruption in the intention to treat population.
Arm S = study arm (switch to maraviroc + darunavir/ritonavir); Arm C = continuation arm (continuation of previous 3-drug therapy).
Fig 4
Fig 4. Evolution of (a-d) blood lipids and (e) renal function as by estimated GFR (CKD-EPI) over the 48 study weeks by randomization arm.
Arm S = study arm (switch to maraviroc + darunavir/ritonavir); Arm C = continuation arm (continuation of previous 3-drug therapy).
See this image and copyright information in PMC

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