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
Author:
Álvarez Hortensia12ORCID, Mocroft Amanda34, Ryom Lene35, Neesgaard Bastian3, Edwards Simon6, Svedhem Veronica7, Günthard Huldrych F8, Zangerle Robert9, Smith Colette10, Castagna Antonella11, d’Arminio Monforte Antonella12, Wit Ferdinand13, Stecher Melanie14ORCID, Lehman Clara14, Mussini Cristina15, Fontas Eric16, González Eva17, Wasmuth Jan-Christian18, Sönnerborg Anders19, De Wit Stéphane20, Chkhartishvili Nikoloz21, Stephan Christoph22, Petoumenos Kathy23, Jaschinski Nadine3, Vannappagari Vani24, Gallant Joel25, Young Lital26, Volny Anne Alain27, Greenberg Lauren34, Martín-Iguacel Raquel28, Poveda Eva29ORCID, Llibre Josep M30, Wit F, Valk M v d, Hillebregt M, Petoumenos K, Law M, Byonanebye D, Hutchinson J, Zangerle R, Appoyer H, Vera J, Clarke A, Broster B, Barbour L, De Wit S, Delforge M, Begovac J, Wandeler G, Stephan C, Bucht M, Chkhartishvili N, Chokoshvili O, d’Arminio Monforte A, Rodano A, Tavelli A, Fanti I, Mussini C, Borghi V, Pradier C, Fontas E, Dollet K, Caissotti C, Casabona J, Miro J M, Smith C, Lampe F, Johnson M, Burns F, Chaloner C, Castagna A, Lazzarin A, Poli A, Sönnerborg A, Falconer K, Svedhem V, Günthard H F, Ledergerber B, Bucher H, Kusejko K, Wasmuth J C, Rockstroh J, Vehreschild J J, Fätkenheuer G, Scherer M, Schulze N, Franke B, Ryom L, Law M, Rooney J, McNicholl I, Vannappagari V, Garges H, Petoumenos K, Wandeler G, Zangerle R, Smith C, De Wit S, Lundgren J, Günthard H F, Young L, Campo R, Lundgren J, Günthard H F, Kowalska J, Raben D, Ryom L, Mocroft A, Rockstroh J, Peters L, Kirk O, Podlekareva D, Volny Anne A, Dedes N, Williams E D, Chkhartishvili N, Zangerle R, Petoumenos K, Law M, Wit F, Necsoi C, Wandeler G, Stephan C, Pradier C, d’Arminio Monforte A, Mussini C, Bruguera A, Bucher H, Sönnerborg A, Vehreschild J J, Wasmuth J C, Smith C, Castagna A, Vera J, Begovac J, Rooney J, McNicholl I, Vannappagari V, Garges H, Young L, Campo R, Ryom L, Mocroft A, Neesgaard B, Greenberg L, Jaschinski N, Bansi-Matharu L, Svedhem-Johansson V, Wit F, Grabmeier-Pfistershammer K, Zangerle R, Hoy J, Bloch M, Braun D, Calmy A, Schüttfort G, Youle M, De Wit S, Mussini C, Zona S, Castagna A, Antinori A, Chkhartishvili N, Bolokadze N, Fontas E, Dollet K, Pradier C, Miro J M, Llibre J M, Vehreschild J J, Schwarze-Zander C, Wasmuth J C, Rockstroh J, Petoumenos K, Law M, Duvivier C, Dragovic G, Radoi R, Oprea C, Vasylyev M, Kowalska J, Matulionyte R, Mulabdic V, Marchetti G, Kuzovatova E, Coppola N, Begovac J, Aho I, Martini S, Bucher H, Harxhi A, Wæhre T, Pharris A, Vassilenko A, Fätkenheuer G, Bogner J, Maagaard A, Jablonowska E, Elbirt D, Marrone G, Leen C, Wyen C, Kundro M, Hathleberger C, Pelchen-Matthews A, Byonanebye D, Fursa O, Roen A, Dahlerup-Rasmussen L, Dedes N, Dixon Williams E, Gallant J, Thorpe D, Vannappagari V, Garges H, Arduino J M, Sklar P, Anne Alain Volny, Dedes Nikos, Mendão Luis, Williams Esther Dixon, Larsen J F, Neesgaard B, Jaschinski N, Fursa O, Valdemaier O, Timiryasova A, Ryom L, Peters L, Jakobsen M L, Kraef C, Gardizi M, Raben D, Elsing T W, Ramesh Kumar L, Shahi S, Andersen K, Reekie J, Mocroft A, Greenberg L, Bansi-Matharu L, Pelchen-Matthews A, Petoumenos K, Byonanebye D, Tusch E, Roen A, Bannister W,
Affiliation:
1. Department of Internal Medicine, Infectious Diseases Unit, Complexo Hospitalario Universitario de Ferrol, Ferrol, SERGAS-A Coruña , Spain 2. Department of Biochemistry, Genetics and Immunology, Universidade de Vigo , Vigo , Spain 3. CHIP, Rigshospitalet, University of Copenhagen , Copenhagen , Denmark 4. Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London , London , United Kingdom 5. Department of Infectious Diseases, Hvidovre University Hospital , Copenhagen , Denmark 6. Department of HIV, Mortimer Market Centre , London , United Kingdom 7. Department of Medicine, Medical Unit Infectious Diseases, Karolinska University Hospital, Karolinska Institutet , Huddinge , Sweden 8. Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich and Institute of Medical Virology, University of Zurich , Zurich , Switzerland 9. Austrian HIV Cohort Study, Medizinische Universität Innsbruck , Innsbruck , Austria 10. The Royal Free HIV Cohort Study, Royal Free Hospital, University College London , London , United Kingdom 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. AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort, HIV Monitoring Foundation , Amsterdam , The Netherlands 14. Division of Infectious Diseases, Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne , Cologne , Germany 15. Modena HIV Cohort, Università degli Studi di Modena , Modena , Italy 16. Nice HIV Cohort, Université Côte d´Azur et Centre Hospitalier Universitaire , Nice , France 17. PISCIS Cohort Study, Centre Estudis Epidemologics de ITS i VIH de Catalunya , Badalona , Spain 18. Medical Department, University Hospital Bonn , Bonn , Germany 19. Swedish InfCare HIV Cohort, Karolinska University Hospital , Stockholm , Sweden 20. CHU Saint-Pierre, Université Libre de Bruxelles , Brussels , Belgium 21. Georgian National AIDS Health Information System, Infectious Diseases, AIDS and Clinical Immunology Research Center , Tbilisi , Georgia 22. Frankfurt HIV Cohort Study, University Hospital Frankfurt, Goethe-University, Infectious Diseases Unit , Frankfurt , Germany 23. The Kirby Institute, University of New South Wales , Sydney , Australia 24. ViiV Healthcare , Research Triangle Park, North Carolina , USA 25. Gilead Sciences , Foster City, California , USA 26. Merck Sharp & Dohme , Luzern , Switzerland 27. European AIDS Treatment Group , Brussels , Belgium 28. Infectious Diseases Department, Odense University Hospital , Odense , Denmark 29. Group of Virology and Pathogenesis, Galicia Sur Health Research Institute (IIS Galicia Sur)–Complexo Hospitalario Universitario de Vigo , Vigo, SERGAS-UVigo , Spain 30. Infectious Diseases Division and Fight Infections Foundation, University Hospital Germans Trias i Pujol , Barcelona , Spain
Abstract
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.
Funder
Austrian HIV Cohort Study Australian HIV Observational Database CHU Saint-Pierre University Hospital Cologne EuroSIDA Frankfurt HIV Cohort Study Georgian National AIDS Health Information System Modena HIV Cohort San Raffaele Scientific Institute Swiss HIV Cohort Study AIDS Therapy Evaluation Royal Free HIV Cohort Study National Health and Medical Research Council Swiss National Science Foundation
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
Cited by
8 articles.
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