TY - JOUR
T1 - Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium
AU - Neesgaard, Bastian
AU - Mocroft, Amanda
AU - Zangerle, Robert
AU - Wit, Ferdinand
AU - Lampe, Fiona
AU - Günthard, Huldrych F.
AU - Necsoi, Coca
AU - Law, Matthew
AU - Mussini, Cristina
AU - Castagna, Antonella
AU - Monforte, Antonella dArminio
AU - Pradier, Christian
AU - Chkhartisvilli, Nikoloz
AU - Reyes-Uruena, Juliana
AU - Vehreschild, J. rg Janne
AU - Wasmuth, Jan-Christian
AU - Sönnerborg, Anders
AU - Stephan, Christoph
AU - Greenberg, Lauren
AU - Llibre, Josep M.
AU - Volny-Anne, Alain
AU - Peters, Lars
AU - Pelchen-Matthews, Annegret
AU - Vannappagari, Vani
AU - Gallant, Joel
AU - Rieger, Armin
AU - Youle, Mike
AU - Braun, Dominique
AU - de Wit, Stephane
AU - Petoumenos, Kathy
AU - Borghi, Vanni
AU - Spagnuolo, Vincenzo
AU - Tsertsvadze, Tengiz
AU - Lundgren, Jens
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85098939001&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pone.0243625
DO - https://doi.org/10.1371/journal.pone.0243625
M3 - Article
C2 - 33382756
SN - 1932-6203
VL - 15
JO - PLOS ONE
JF - PLOS ONE
IS - 12 December
M1 - e0243625
ER -