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Clinical value of ultradeep HIV-1 genotyping and tropism testing in late presenters with advanced disease
- Source :
- AIDS, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname
- Publication Year :
- 2015
-
Abstract
- 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/mu l 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/mu l 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/mu l 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. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
- Subjects :
- Oncology
Adult
Male
medicine.medical_specialty
Efavirenz
Genotyping Techniques
Immunology
HIV Infections
Biology
law.invention
HIV-1 viral tropism
chemistry.chemical_compound
Randomized controlled trial
law
advanced HIV disease
Internal medicine
Antiretroviral Therapy, Highly Active
Drug Resistance, Viral
virologic failure
medicine
Immunology and Allergy
Humans
Prospective Studies
Prospective cohort study
Retrospective Studies
Reverse-transcriptase inhibitor
minority drug resistance mutations
Proportional hazards model
Retrospective cohort study
Sequence Analysis, DNA
Middle Aged
Confidence interval
ultradeep sequencing
Viral Tropism
Infectious Diseases
Treatment Outcome
chemistry
Anti-Retroviral Agents
Mutation
Tissue tropism
HIV-1
Female
medicine.drug
Subjects
Details
- ISSN :
- 14735571 and 02699370
- Volume :
- 29
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- AIDS (London, England)
- Accession number :
- edsair.doi.dedup.....276dd0cdfd881ad970071cff7d92d5e2