Journal Article

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

Vannappagari, Vani, Greenberg, Lauren, Castagna, Antonella, Pradier, Christian, Ryom, Lene, Reyes-Uruena, Juliana, Braun, Dominique, Petoumenos, Kathy, Sönnerborg, Anders, De Wit, Stephane, Tsertsvadze, Tengiz, Rieger, Armin, Chkhartisvilli, Nikoloz, Günthard, Huldrych F., Spagnuolo, Vincenzo, Mocroft, Amanda, Llibre, Josep M., Peters, Lars, Wit, Ferdinand, Vehreschild, Jörg Janne, Neesgaard, Bastian, Monforte, Antonella d’Arminio, Lundgren, Jens, Stephan, Christoph, Wasmuth, Jan-Christian, Volny-Anne, Alain, Youle, Mike, Lampe, Fiona, Pelchen-Matthews, Annegret, Gallant, Joel, Borghi, Vanni, Zangerle, Robert, Necsoi, Coca, Law, Matthew, Mussini, Cristina

2020

Overview

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. 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. 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). 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Adult / AIDS / Antiretroviral agents / Antiretroviral drugs / Antiretroviral therapy / Biology and Life Sciences / Care and treatment / CD4 antigen / CD4 Lymphocyte Count / Cohort Studies / Confidence intervals / Consortia / Diabetes / Epidemiology / Female / HIV / HIV - drug effects / HIV - immunology / HIV infection / HIV Infections - drug therapy / HIV Infections - immunology / HIV Infections - virology / HIV Integrase Inhibitors - therapeutic use / HIV Protease Inhibitors - therapeutic use / Hospitals / Human immunodeficiency virus / Humans / Immune response / Immunology / Infectious diseases / Integrase / Integrase inhibitors / Male / Medicine and Health Sciences / Middle Aged / Non-nucleoside reverse transcriptase inhibitors / Nucleotides / Patient outcomes / People and Places / Protease inhibitors / Proteinase inhibitors / Regression analysis / Reverse Transcriptase Inhibitors - therapeutic use / RNA-directed DNA polymerase / Sensitivity analysis / Statistical analysis / Testing / Treatment Outcome / Viral Load - drug effects / Viral Load - immunology / Virology / Windows (intervals) / World population