Effectiveness of Dolutegravir-Based Regimens as Either First Line or Switch Antiretroviral Therapy: Data from the ICONA Cohort

Abstract

Background We aimed to estimate the risk of discontinuation (TD) and virological failure (VF) of dolutegravir (DTG)-based regimens. Methods We performed a multicentre, observational study including all antiretroviral therapy (ART)-naA¯ve and virologically suppressed treatment-experienced (TE) patients from the ICONA cohort who started DTG for the first time. We estimated time to DTG-TD and VF using Kaplan-Meier curves. We used Cox regression model to assess predictors of DTG-TD. Findings 1,679 individuals (932 ART-naive, 747 TE) included. The one- and two-year probabilities (95% CI) of DTG-TD were 6⋅7% (4⋅9-8⋅4) and 11⋅5% (8⋅7-14⋅3) for ART-naive and 6⋅6% (4⋅6-8⋅6) and 7⋅6% (5⋅4-9⋅8) for TE subjects. In both ART-naive and TE, DTG-TD was mainly driven by toxicity with an estimated risk (95% CI) of 4⋅0% (2⋅6-5⋅4) and 2⋅5% (1⋅3-3⋅6) by one year and 5⋅6% (3⋅8-7⋅5) and 4⋅0% (2⋅4-5⋅6) by two years, respectively. Neuropsychiatric events were the main reason for DTG-TD in both ART-naive (2⋅1%) and TE (1⋅7%) patients. In ART-naive, a concomitant AIDS diagnosis predicted the risk of DTG-TD for any reason (aRH=3⋅38, p=0⋅001) whereas starting DTG in combination with abacavir (ABC) predicted DTG-TD for toxicity (aRH=3⋅30, p=0⋅009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of DTG-TD for any reason (aHR 2⋅50, p=0⋅037 for ABC-based triple-therapies, aHR 3⋅56, p=0.012 for tenofovir-based) and for toxicity (aHR 5⋅26, p=0⋅030 for ABC-based, aHR 6⋅60,p=0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of VF were 1⋅2% (0⋅3-2⋅0) and 4⋅6% (2⋅7-6⋅5) in the ART naive group and 2⋅2% (1⋅0-3⋅3) and 2⋅9% (1⋅5-4⋅3) in the TE group. Interpretation DTG showed excellent efficacy and tolerability both in ART-naive and TE patients. The low risk of toxicities limiting DTG treatment provide reassuring information in the light of the forthcoming transition to DTG-based first-line therapy in resource-limited countries. Funding: Viiv Healthcare International. Declaration of Interest: AM, ACL, AT, FM and FV have nothing to disclose. SR outside the submitted work reports grants personal fees and non-financial support from ViiV Healthcare,Gilead Sciences and Janssen-Cilag, personal fees and non-financial support from Bristol Myers Squibb and personal fees from Merck Sharp and Dohme. FCS outside the submitted work reports personal fees from Gilead Sciences, Bristol Meyers Squibb, Abbvie, Roche Diagnostic, Janssen-Cilag, Abbott Molecular and ViiV Healthcare, grants and personal fees from Merck Sharp and Dohme and grants from Italian Ministry of Instruction University and Research. AC outside the submitted work reports grants and personal fees from ViiV Healthcare and personal fees from Merck Sharp and Dohme and Janssen-Cilag. ADL outside the submitted work reports grants and personal fees from ViiV 331 Healthcare, Merck Sharp and Dohme and Gilead Sciences and personal fees from Janssen-Cilag and Abbvie. GM outside the submitted work reports personal fees from Gilead Sciences and ViiV Healthcare. AA outside the submitted work reports grants, personal fees and non-financial support from Gilead Sciences, ViiV Healthcare and Bristol Myers Squibb, grants and personal fees from Janssen-Cilag, personal fees from Merck Sharp and Dohme and personal fees and non financial support from Abbvie. AdAM outside the submitted work reports grants and personal fees from Gilead Sciences, ViiV Healthcare and Merck Sharp and Dohme and personal fees from Janssen and Bristol Myers Squibb. Ethical Approval: The Icona Foundation study was approved by the Ethics Committee (IRB) of each participating institution. All of the individuals enrolled provided a written informed consent at the time of the enrolment. All procedures of the study were performed in accordance with the 1964 Helsinki declaration and its later amendments.