Plasma Human Immunodeficiency Virus 1 RNA and CD4+ T-Cell Counts Are Determinants of Virological Nonsuppression Outcomes With Initial Integrase Inhibitor-Based Regimens: A Prospective RESPOND Cohort Study
Hortensia Álvarez, Amanda Mocroft, Lene Ryom, Bastian Neesgaard, Simon Edwards, Veronica Svedhem, Huldrych F. Günthard, Robert Zangerle, Colette Smith, Antonella Castagna, Antonella d’Arminio Monforte, Ferdinand W.N.M. Wit, Melanie Stecher, Clara Lehman, Cristina Mussini, Éric Fontas, Eva González, Jan‐Christian Wasmuth, Anders Sönnerborg, Stéphane De Wit, Nikoloz Chkhartishvili, Christoph Stephan, Kathy Petoumenos, Nadine Jaschinski, Vani Vannappagari, Joel E. Gallant, Lital Young, Alain Volny Anne, Lauren Greenberg, Raquel Martín-Iguacel, Eva Poveda, Josep M. Llibre, Ferdinand Wit, Marc van der Valk, M Hillebregt, Kathy Petoumenos, M Law, D Byonanebye, J Hutchinson, Robert Zangerle, H Appoyer, J Vera, A Clarke, B Broster, L Barbour, S De Wit, M Delforge, J Begovac, Gilles Wandeler, Christoph Stephan, M Bucht, Nikoloz Chkhartishvili, Otar Chokoshvili, Antonella d’Arminio Monforte, A Rodano, A Tavelli, Iuri Fanti, Cristina Mussini, Vanni Borghi, C Pradier, Éric Fontas, K Dollet, C Caissotti, Jordi Casabona, JM Miró, Colette Smith, Fiona Lampe, M. Johnson, F Burns, C Chaloner, Antonella Castagna, Adriano Lazzarin, Alessandro Poli, Anders Sönnerborg, Karolin Falconer, Veronica Svedhem, Huldrych F. Günthard, B Ledergerber, H C Bucher, K Kusejko, J C Wasmuth, J Rockstroh, Jörg Janne Vehreschild, G Fätkenheuer, M Scherer, Nick Schulze, Bernd Franke, Lene Ryom, M Law, J. Rooney, I McNicholl, Vani Vannappagari, H Garges, Kathy Petoumenos, Gilles Wandeler, Robert Zangerle, Colette Smith, S De Wit, Jens Lundgren, Huldrych F. Günthard
Abstract
BACKGROUND: There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. METHODS: We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. RESULTS: Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. CONCLUSIONS: Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.