Clinical value of ultradeep HIV-1 genotyping and tropism testing in late presenters with advanced disease

Maria Casadella, Christian Manzardo, Marc Noguera-Julian, Elena Ferrer, Pere Domingo, Susana Perez-Alvarez, Daniel Podzamczer, Montserrat Plana, Bonaventura Clotet, Jose B. Gatell, Jose M. Miro, Roger Paredes

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7 Citations (Scopus)

Abstract

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Objective: This article aims to investigate if the detection of preexisting drug-resistant minority variant (DRMV) and/or X4 HIV-1 variants could improve the efficacy of firstline combined antiretroviral therapy (ART) in late presenters. Design: Post-hoc, combined analysis of two open-label, prospective, randomized clinical trials comparing first-line ART with efavirenz (EFV) vs. ritonavir-boosted protease inhibitor (PI/r)-based regimens in ART-naive, HIV-1-infected patients, with CD4 T-cell counts less than 100 cells/ml and wild-type HIV-1 by bulk sequencing. Methods: Pre-ART samples were reanalyzed for the presence of DRMVs and X4 HIV-1 using 454 sequencing. KaplanMeier curves and Cox regression were used to evaluate the association between X4 HIV and DRMVs and risk of virological failure. Results: From 141 evaluable patients, 57 received EFV, and 84 received PI/r, including first-line ART. Median pre-ART CD4 T-cell counts and HIV-1 RNA levels were 39 cells/ ml and 257 424 copies/ml, respectively; 35.5% of patients had X4 HIV variants. Detection of DRMVs leading to an ART-specific cumulative HIVdb score of at least 10 increased the risk of virological failure in patients initiating EFV [log-rank P0.048, hazard ratio4.3 (95% confidence interval: 0.8, 25.0), P0.074], but not in those starting PI/r. Presence of X4 HIV did not affect virological outcomes, but was associated with impaired CD4 T-cell count recovery over 2 years (214 vs. 315 cells/ml with X4 vs. R5 HIV-1 tropism, respectively, P0.017). Conclusion: Accounting for preexisting DRMVs may improve the outcomes of first-line nonnucleoside reverse transcriptase inhibitor-based ART in late presenters with advanced immune suppression. Presence of X4 HIV-1 at diagnosis predicts impaired immune restoration under ART.
Original languageEnglish
Pages (from-to)1493-1504
JournalAIDS
Volume29
Issue number12
DOIs
Publication statusPublished - 31 Jul 2015

Keywords

  • Advanced HIV disease
  • HIV-1 viral tropism
  • Minority drug resistance mutations
  • Ultradeep sequencing
  • Virologic failure

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    Casadella, M., Manzardo, C., Noguera-Julian, M., Ferrer, E., Domingo, P., Perez-Alvarez, S., Podzamczer, D., Plana, M., Clotet, B., Gatell, J. B., Miro, J. M., & Paredes, R. (2015). Clinical value of ultradeep HIV-1 genotyping and tropism testing in late presenters with advanced disease. AIDS, 29(12), 1493-1504. https://doi.org/10.1097/QAD.0000000000000748