Predictors of Virological Failure and Time to Viral Suppression of First-Line Integrase Inhibitor–Based Antiretroviral Treatment
Author:
Pyngottu Ashima12, Scherrer Alexandra U12, Kouyos Roger12, Huber Michael2, Hirsch Hans3, Perreau Matthieu4, Yerly Sabine5, Calmy Alexandra5, Cavassini Matthias6, Stöckle Marcel3, Furrer Hansjakob7, Vernazza Pietro8, Bernasconi Enos9, Günthard Huldrych F12, Aebi-Popp K, Anagnostopoulos A, Battegay M, Bernasconi E, Böni J, Braun D L, Bucher H C, Calmy A, Cavassini M, Ciuffi A, Dollenmaier G, Egger M, Elzi L, Fehr J, Fellay J, Furrer H, Fux C A, Günthard H F, Haerry D, Hasse B, Hirsch H H, Hoffmann M, Hösli I, Huber M, Kahlert C R, Kaiser L, Keiser O, Klimkait T, Kouyos R D, Kovari H, Ledergerber B, Martinetti G, Martinez de Tejada B, Marzolini C, Metzner K J, Müller N, Nicca D, Paioni P, Pantaleo G, Perreau M, Rauch A, Rudin C, Scherrer A U, Schmid P, Speck R, Stöckle M, Tarr P, Trkola A, Vernazza P, Wandeler G, Weber R, Yerly S,
Affiliation:
1. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland 2. Institute of Medical Virology, University of Zurich, Zurich, Switzerland 3. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland 4. Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland; University of Lausanne, Lausanne, Switzerland 5. Laboratory of Virology and Division of Infectious Diseases, Geneva University Hospital, University of Geneva, Geneva, Switzerland 6. Division of Infectious Diseases, Lausanne University Hospital, Lausanne, Switzerland 7. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland 8. Division of Infectious Diseases, Cantonal Hospital St. Gallen, St. Gallen, Switzerland 9. Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland
Abstract
Abstract
Background
Integrase strand transfer inhibitors (InSTIs) are recommended for first-line treatment of persons with human immunodeficiency virus (HIV). We identified risk factors, including baseline minor InSTI resistance mutations, for treatment failure of InSTI-based regimens.
Methods
We studied time-to-treatment failure and time to viral suppression among 1419 drug-naive patients in the Swiss HIV Cohort Study. We performed Cox regression models adjusted for demographic factors, baseline HIV RNA/CD4 cell counts, AIDS-defining events, and the type of InSTI. In 646 patients with a baseline genotypic resistance test of the integrase, we studied the impact of minor integrase resistance mutations.
Results
We observed 121 virological failures during 18 447 person-years of follow-up. A baseline viral load ≥100 000 copies/mL (multivariable hazard ratio [mHR], 2.2; 95% confidence interval [CI], 1.3–3.6) and an AIDS-defining event (mHR, 1.8; 95% CI. 1.1–3.0) were associated with treatment failure. CD4 counts between 200 and 500 cells/µL (mHR, 0.5; 95% CI, .3–.8) and >500 cells/µL (mHR, 0.4; 95% CI, .2–.7) were protective. Time to suppression was shorter in lower viral load strata (mHR, 0.7; 95% CI, .6–.8) and in dolutegravir-based therapy (mHR, 1.2; 95% CI, 1.0–1.4). Minor resistance mutations were found at baseline in 104 of 646 (16%) patients with no effect on treatment outcome.
Conclusions
Factors associated with treatment failure on InSTI-based first-line regimen remained similar to those of older treatments, in particular high viral load and low CD4 counts.
Funder
Swiss National Science Foundation SHCS Research Foundation Yvonne Jacob Foundation
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
Cited by
22 articles.
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