Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort.

Abstract

INTRODUCTION:

Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals.

METHODS:

We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan-Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation.

RESULTS:

About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of 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 discontinuation for any reason (adjusted hazard ratio (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 virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group.

CONCLUSIONS:

In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice.

• Authors: Annalisa Mondi, Alessandro Cozzi-Lepri, Alessandro Tavelli, Stefano Rusconi, Francesca Vichi, Francesca Ceccherini-Silberstein, Andrea Calcagno, Andrea De Luca, Franco Maggiolo, Giulia Marchetti, Andrea Antinori, Antonella d'Arminio Monforte, Icona Foundation Study Group
• Journal: Journal of the International AIDS Society (J Int AIDS Soc) Vol. 22 Issue 1 Pg. e25227 (01 2019) ISSN: 1758-2652 [Electronic] Switzerland
• PMID: 30663278 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

Chemical References

• Anti-HIV Agents
• Dideoxynucleosides
• Heterocyclic Compounds, 3-Ring
• Oxazines
• Piperazines
• Pyridones
• Tenofovir
• dolutegravir
• abacavir

Topics

• Adult
• Anti-HIV Agents (therapeutic use)
• Cohort Studies
• Dideoxynucleosides (therapeutic use)
• Female
• HIV Infections (drug therapy)
• Heterocyclic Compounds, 3-Ring (therapeutic use)
• Humans
• Italy
• Male
• Middle Aged
• Oxazines
• Piperazines
• Prospective Studies
• Pyridones
• Retrospective Studies
• Tenofovir (therapeutic use)
• Treatment Outcome