Related Experiment Video
Updated: May 16, 2026
07:06
Prediction of HIV-1 Coreceptor Usage (Tropism) by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
HIV-1 dynamics and coreceptor usage in Maraviroc-treated patients with ongoing replication
P Recordon-Pinson1, S Raymond, P Bellecave
1Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Universite Bordeaux 2, Bordeaux, France.
Antimicrobial Agents and Chemotherapy
|December 5, 2012
Summary
Human immunodeficiency virus type 1 (HIV-1) can evolve resistance to maraviroc (MVC) by selecting for X4-tropic variants or MVC-resistant R5-tropic isolates. Viral dynamics in patients experiencing virological failure on MVC-containing regimens are not well understood.
Area of Science:
- Virology
- Immunology
- Drug Resistance
Background:
- Maraviroc (MVC) is a C-C chemokine receptor type 5 (CCR5) antagonist used in HIV-1 treatment.
- HIV-1 evolution under MVC pressure can lead to X4-tropic variants or MVC-resistant R5-tropic isolates.
- The viral dynamics of HIV-1 variants during virological failure (VF) on MVC-containing regimens require further investigation.
Purpose of the Study:
- To investigate the V3 loop evolution of HIV-1 under MVC pressure.
- To analyze coreceptor usage and HIV-1 quasispecies in patients with VF on MVC.
- To understand the mechanisms of MVC resistance and viral tropism changes.
Main Methods:
- Utilized bulk population sequencing and ultradeep sequencing to analyze HIV-1 V3 loop evolution.
- Examined viral quasispecies composition before and during MVC therapy.
- Tracked changes in coreceptor usage (R5 vs. X4 tropism) up to the point of virological failure.
Main Results:
- Most patients did not have detectable minority X4 variants at baseline.
- Three distinct patterns of viral evolution were observed leading to virological failure:
- 1. Emergence of pre-existing X4 variants.
- 2. De novo selection of R5 variants with V3 loop mutations.
- 3. Replication of R5 variants without selection of known mutations.
Conclusions:
- HIV-1 evolution under MVC pressure can follow multiple pathways.
- Understanding these pathways is crucial for managing treatment failure and optimizing antiretroviral therapy.
- Further research into HIV-1 quasispecies dynamics can inform the development of more effective treatment strategies.
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