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Home / Publications / Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-naive individuals: results from a European multi-cohort study

Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-naive individuals: results from a European multi-cohort study

  • Authors: Barbara Rossetti, Massimiliano Fabbiani, Domenico Di Carlo, Francesca Incardona, Ana Abecasis, Perpetua Gomes, Anna Maria Geretti, Carole Seguin-Devaux, Federico Garcia, Rolf Kaiser, Sara Modica, Adrian Shallvari, Anders Sönnerborg, Maurizio Zazzi, EuResist Network, INTEGRATE study group
  • Publication Year: 2021
  • Journal: Journal of Antimicrobial Chemotherapy, 76(9), pp 2394–2399
  • Link: https://doi.org/10.1093/jac/dkab200

ABSTRACT

‘Background:’

INSTIs have become a pillar of first-line ART. Real-world data are needed to assess their effectiveness in routine care.

‘Objectives:’

We analysed ART-naive patients who started INSTI-based regimens in 2012–19 whose data were collected by INTEGRATE, a European collaborative study including seven national cohorts.

‘Methods:’

Kaplan–Meier analyses assessed time to virological failure (VF), defined as one viral load (VL) ≥1000 copies/mL, two consecutive VLs ≥50 copies/mL, or one VL ≥50 copies/mL followed by treatment change after ≥24 weeks of follow-up, and time to INSTIs discontinuation (INSTI-DC) for any reason. Factors associated with VF and INSTI-DC were explored by logistic regression analysis.

‘Results:’

Of 2976 regimens started, 1901 (63.9%) contained dolutegravir, 631 (21.2%) elvitegravir and 444 (14.9%) raltegravir. The 1 year estimated probabilities of VF and INSTI-DC were 5.6% (95% CI 4.5–6.7) and 16.2% (95% CI 14.9–17.6), respectively, and were higher for raltegravir versus both elvitegravir and dolutegravir. A baseline VL ≥100 000 copies/mL [adjusted HR (aHR) 2.17, 95% CI 1.55–3.04, P < 0.001] increased the risk of VF, while a pre-treatment CD4 count ≥200 cells/mm3 reduced the risk (aHR 0.52, 95% CI 0.37–0.74, P < 0.001). Predictors of INSTI-DC included use of raltegravir versus dolutegravir (aHR 3.03, 95% CI 2.34–3.92, P < 0.001), use of >3 drugs versus 3 drugs (aHR 2.73, 95% CI 1.55–4.79, P < 0.001) and starting ART following availability of dolutegravir (aHR 0.64, 95% CI 0.48–0.83, P = 0.001). Major INSTI mutations indicative of transmitted drug resistance occurred in 2/1114 (0.2%) individuals.

‘Conclusions:’

This large multi-cohort study indicates high effectiveness of elvitegravir- or dolutegravir-based first-line ART in routine practice across Europe.

KEYWORDS

mutation; drug resistance; cd4 count determination procedure; follow-up; integrase; integrase inhibitors; aryl hydrocarbon receptor; viral load result; virology; hiv infections; elvitegravir; raltegravir; dolutegravir; transfer technique; treatment modification; therapy naive.

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About GHTM

GHTM is a R&D Unit that brings together researchers with a track record in Tropical Medicine and International & Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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