Clinical value of ultradeep HIV-1 genotyping and tropism testing in late presenters with advanced disease
Related Experiment Video
Updated: Apr 5, 2026
Prediction of HIV-1 Coreceptor Usage Tropism by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
Maria Casadellà1, Christian Manzardo, Marc Noguera-Julian
1aIrsiCaixa AIDS Research Institute, Universitat Autònoma de Barcelona, Badalona bHospital Clínic-IDIBAPS, University of Barcelona, Barcelona cUVIC-UCC, Vic dHospital Bellvitge-IDIBELL, University of Barcelona eHospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona fHIV Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain. *Maria Casadellà and Christian Manzardo contributed equally to the writing of this article. †The ADVANZ and ADVANZ-3 investigators are listed under the Acknowledgements section.
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 first-line 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/μl 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. Kaplan-Meier 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/μl 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 P = 0.048, hazard ratio = 4.3 (95% confidence interval: 0.8, 25.0), P = 0.074], 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/μl with X4 vs. R5 HIV-1 tropism, respectively, P = 0.017).
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.
