Bastian Neesgaard1, Amanda Mocroft2, Robert Zangerle3, Ferdinand Wit4, Fiona Lampe5, Huldrych F Günthard6,7, Coca Necsoi8, Matthew Law9, Cristina Mussini10, Antonella Castagna11, Antonella d'Arminio Monforte12, Christian Pradier13, Nikoloz Chkhartisvilli14, Juliana Reyes-Uruena15, Jörg Janne Vehreschild16,17, Jan-Christian Wasmuth18, Anders Sönnerborg19, Christoph Stephan20, Lauren Greenberg2, Josep M Llibre21, Alain Volny-Anne22, Lars Peters1, Annegret Pelchen-Matthews2, Vani Vannappagari23, Joel Gallant24, Armin Rieger25, Mike Youle5, Dominique Braun6,7, Stephane De Wit8, Kathy Petoumenos9, Vanni Borghi10, Vincenzo Spagnuolo11, Tengiz Tsertsvadze14, Jens Lundgren1, Lene Ryom1. 1. CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 2. Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, United Kingdom. 3. Austrian HIV Cohort Study (AHIVCOS), Medizinische Universität Innsbruck, Innsbruck, Austria. 4. AIDS Therapy Evaluation in the Netherlands Cohort (ATHENA), Stichting HIV Monitoring (SHM), Amsterdam, Netherlands. 5. Royal Free Hospital, University College London, London, United Kingdom. 6. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland. 7. Institute of Medical Virology, University of Zurich, Zurich, Switzerland. 8. CHU Saint-Pierre, Centre de Recherche en Maladies Infectieuses a.s.b.l., Brussels, Belgium. 9. The Australian HIV Observational Database (AHOD), UNSW, Sydney, Australia. 10. Modena HIV Cohort, Università degli Studi di Modena, Modena, Italy. 11. San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milano, Italy. 12. Italian Cohort Naive Antiretrovirals (ICONA), ASST Santi Paolo e Carlo, Milano, Italy. 13. Nice HIV Cohort, Université Côte d'Azur et Centre Hospitalier Universitaire, Nice, France. 14. Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi, Georgia. 15. PISCIS Cohort, Centre d'Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), CIBERESP, Badalona, Spain. 16. Medical Department 2, Hematology/Oncology, University Hospital of Frankfurt, Frankfurt, Germany. 17. Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany. 18. University Hospital Bonn, Bonn, Germany. 19. Swedish InfCare HIV Cohort, Karolinska University Hospital, Stockholm, Sweden. 20. Infectious Diseases Unit, Medical Dept. no.2, Frankfurt University Hospital, Goethe-University, Frankfurt, Germany. 21. Infectious Diseases and Fight AIDS Foundation, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain. 22. European AIDS Treatment Group (EATG), Brussels, Belgium. 23. ViiV Healthcare, Research Triangle, North Carolina, United States of America. 24. Gilead Sciences, Foster City, California, United States of America. 25. Wiener Medizinische Universität, Vienna, Austria.
Abstract
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.
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.
Authors: Dathan M Byonanebye; Mark N Polizzotto; Bastian Neesgaard; Mario Sarcletti; Raimonda Matulionyte; Dominique L Braun; Antonella Castagna; Stéphane de Wit; Ferdinand Wit; Eric Fontas; Jörg Janne Vehreschild; Jan Vesterbacka; Lauren Greenberg; Camilla Hatleberg; Harmony Garges; Joel Gallant; Alain Volny Anne; Angela Öllinger; Iwona Mozer-Lisewska; Bernard Surial; Vincenzo Spagnuolo; Coca Necsoi; Marc van der Valk; Amanda Mocroft; Matthew Law; Lene Ryom; Kathy Petoumenos Journal: HIV Med Date: 2022-03-01 Impact factor: 3.094