Trends and factors associated with modification or discontinuation of the initial antiretroviral regimen during the first year of treatment in the Turkish HIV-TR Cohort, 2011\u20132017

Volkan Korten,On Behalf Of The Hiv-Tr Study Group ,Taner Yıldırmak,Başak Dokuzoğuz,Ayşe Willke,Ilkay Karaoğlan,Mehmet Gönen,Figen Kaptan,Önder Ergönül,Deniz Gökengin,Dilara Inan,Serap Gencer,Haluk Eraksoy,Gülhan Eren

doi:10.1186/s12981-020-00328-6

Abstract

BackgroundThere is limited evidence on the modification or stopping of antiretroviral therapy (ART) regimens, including novel antiretroviral drugs. The aim of this study was to evaluate the discontinuation of first ART before and after the availability of better tolerated and less complex regimens by comparing the frequency, reasons and associations with patient characteristics.MethodsA total of 3019 ART-naive patients registered in the HIV-TR cohort who started ART between Jan 2011 and Feb 2017 were studied. Only the first modification within the first year of treatment for each patient was included in the analyses. Reasons were classified as listed in the coded form in the web-based database. Cumulative incidences were analysed using competing risk function and factors associated with discontinuation of the ART regimen were examined using Cox proportional hazards models and Fine-Gray competing risk regression models.ResultsThe initial ART regimen was discontinued in 351 out of 3019 eligible patients (11.6%) within the first year. The main reason for discontinuation was intolerance/toxicity (45.0%), followed by treatment simplification (9.7%), patient willingness (7.4%), poor compliance (7.1%), prevention of future toxicities (6.0%), virologic failure (5.4%), and provider preference (5.4%). Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based (aHR = 4.4, [95% CI 3.0–6.4]; p < 0.0001) or protease inhibitor (PI)-based regimens (aHR = 4.3, [95% CI 3.1–6.0]; p < 0.0001) relative to integrase strand transfer inhibitor (InSTI)-based regimens were significantly associated with ART discontinuation. ART initiated at a later period (2015-Feb 2017) (aHR = 0.6, [95% CI 0.4–0.9]; p < 0.0001) was less likely to be discontinued. A lower rate of treatment discontinuation for intolerance/toxicity was observed with InSTI-based regimens (2.0%) than with NNRTI- (6.6%) and PI-based regimens (7.5%) (p < 0.001). The percentage of patients who achieved HIV RNA < 200 copies/mL within 12 months of ART initiation was 91% in the ART discontinued group vs. 94% in the continued group (p > 0.05).ConclusionART discontinuation due to intolerance/toxicity and virologic failure decreased over time. InSTI-based regimens were less likely to be discontinued than PI- and NNRTI-based ART.

Highlights

There is limited evidence on the modification or stopping of antiretroviral therapy (ART) regimens, including novel antiretroviral drugs
ART discontinuation due to intolerance/toxicity and virologic failure decreased over time
integrase strand transfer inhibitor (InSTI)-based regimens were less likely to be discontinued than protease inhibitor (PI)- and nucleoside reverse transcriptase inhibitor (NNRTI)-based ART

Summary

Introduction

There is limited evidence on the modification or stopping of antiretroviral therapy (ART) regimens, including novel antiretroviral drugs. The rates of virologic failure with initial ART regimens are decreasing both in clinical trials and in observational cohorts with newer drugs [2, 3]. Discontinuation or modification of the ART regimen is still reported in a minority of patients, especially within the first year, and drug intolerance or toxicity rather than virologic failure is the major reason for discontinuation [4]. The majority of new drugs in various ART classes were introduced in Turkey just a few years later than their launch in resource-rich European countries, and they are accessible for PLWH without any restrictions. Providers have usually initiated locally available ART regimens according to the latest United States Department of Health and Human Services (DHHS) or the European AIDS Clinical Society (EACS) guidelines. The first National Guideline for the Management of HIV [5] was published by the Turkish Ministry of Health in late 2013; this guidance included recommendations similar to those in the EACS guidelines released in 2013, and its possible impacts on the choice of ART regimens would be expected to occur after 2014

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