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Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium

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  • Bastian Neesgaard (Member of study group)
  • Lars Peters (Member of study group)
  • Amanda Mocroft
  • Robert Zangerle
  • Ferdinand Wit
  • Fiona Lampe
  • Huldrych F Günthard
  • Coca Necsoi
  • Matthew Law
  • Cristina Mussini
  • Antonella Castagna
  • Antonella d'Arminio Monforte
  • Christian Pradier
  • Nikoloz Chkhartisvilli
  • Juliana Reyes-Uruena
  • Jörg Janne Vehreschild
  • Jan-Christian Wasmuth
  • Anders Sönnerborg
  • Christoph Stephan
  • Lauren Greenberg
  • Josep M Llibre
  • Alain Volny-Anne
  • Annegret Pelchen-Matthews
  • Vani Vannappagari
  • Joel Gallant
  • Armin Rieger
  • Mike Youle
  • Dominique Braun
  • Stephane De Wit
  • Kathy Petoumenos
  • Vanni Borghi
  • Vincenzo Spagnuolo
  • Tengiz Tsertsvadze
  • Jens Lundgren
  • Lene Ryom
  • RESPOND Study Group
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OBJECTIVES: To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting.

METHODS: Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) <200 copies/mL and failure as at least one of: VL ≥200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death. In addition, on-treatment analysis including only individuals with known VL and no regimen changes was performed. Favorable immunologic response was defined as a 25% increase in CD4 count or as reaching ≥750 CD4 cells/μL.

RESULTS: Between January 2012 and January 2019, 13,703 (33.0% ART-naïve) individuals were included, of whom 7,147 started/switched to a regimen with an INSTI, 3,102 to a PI/b and 3,454 to an NNRTI-containing regimen. The main reason for cTO failure in all treatment groups were changes in ART regimen. Compared to INSTIs, the adjusted odds ratio (aOR) of cTO success was significantly lower for PI/b (0.74 [95% confidence interval, CI 0.67-0.82], p <0.001), but similar for NNRTIs (1.07 [CI 0.97-1.17], p = 0.11). On-treatment analysis and sensitivity analyses using a VL cut-off of 50 copies/mL were consistent. Compared to INSTIs, the aORs of a 25% increase in CD4 count were lower for NNRTIs (0.80 [CI 0.71-0.91], p<0.001) and PI/b (0.87 [CI 0.76-0.99], p = 0.04).

CONCLUSION: In this large analysis of a real-world population, cTO and on-treatment success were similar between INSTIs and NNRTIs, but lower for PI/b, though residual confounding cannot be fully excluded. Obtaining favorable immunologic outcomes were more likely for INSTIs than the other drug classes.

Original languageEnglish
Article numbere0243625
JournalPLoS One
Volume15
Issue number12 December
Pages (from-to)e0243625
ISSN1932-6203
DOIs
Publication statusPublished - Dec 2020

ID: 61632784