Restricted HIV-1 diversity in people with HIV and exceptionally low viral reservoirs
8 affiliations
- 1IrsiCaixa
- 2Department of Cellular Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona
- 3Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University
- 4Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health
- 5CIBERINFEC, Carlos III Health Institute
- 6University of Vic – Central University of Catalonia (UVic-UCC)
- 7Catalan Institution for Research and Advanced Studies (ICREA)
- 8Germans Trias i Pujol Research Institute (IGTP)
Abstract
Background: HIV-1 cure strategies aim to eradicate viral reservoirs that persist despite effective antiretroviral therapy (ART). Low Viral Reservoir Treated (LoViReT) individuals—characterized by exceptionally low proviral DNA levels during ART—offer a unique model to investigate mechanisms underlying reservoir restriction. This study characterizes the genetic features of HIV-1 populations within blood-derived reservoirs of LoViReT individuals.
Methods: We sequenced regions of gag , pol , and env genes from 19 LoViReTs and 21 matched ART-treated controls, defined by proviral DNA levels of <100 and >100 HIV-1-DNA copies/10 ⁶ CD4 ⁺ T-cells, respectively. Paired pre-ART samples from 7 LoViReTs and 8 controls were also analyzed. Genetic diversity was assessed using Shannon entropy and intra-quasispecies weighted genetic distance. Phylogenetic analyses and statistical modeling were performed to compare viral populations and explore viral-host associations between groups.
Findings: LoViReT individuals exhibited significantly lower intra-host Shannon entropy under ART than controls, with env gene contributing most to this difference. Reconstructed quasispecies haplotypes confirmed reduced viral diversity in LoViReT participants, particularly in env . A subset of LoViReTs also showed increased APOBEC-mediated hypermutation in pol , suggesting greater accumulation of deleterious mutations. Matched pre- and post-ART sequences indicated a similar trend toward reduced diversity before treatment initiation in LoViReTs with increased genetic frequencies of matched HLA-restricted epitopes.
Interpretation: These findings indicate that LoViReT individuals maintain a less diverse viral reservoir, potentially reflecting differential immune patterns before therapy and explaining their reduced reservoir size during ART.
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BibTeX
@article{gonzaleznavarro2026restricted,
title = {{Restricted HIV-1 diversity in people with HIV and exceptionally low viral reservoirs}},
author = {Irene González-Navarro and Ramon Lorenzo-Redondo and Cristina Gálvez and Victor Urrea and Lidia Garrido-Sanz and Javier Martinez-Picado and Maria Salgado},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1904455},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1904455/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Restricted HIV-1 diversity in people with HIV and exceptionally low viral reservoirs
AU - Irene González-Navarro
AU - Ramon Lorenzo-Redondo
AU - Cristina Gálvez
AU - Victor Urrea
AU - Lidia Garrido-Sanz
AU - Javier Martinez-Picado
AU - Maria Salgado
PY - 2026
DA - 2026/10/30
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1904455
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1904455/full
AB - Background: HIV-1 cure strategies aim to eradicate viral reservoirs that persist despite effective antiretroviral therapy (ART). Low Viral Reservoir Treated (LoViReT) individuals—characterized by exceptionally low proviral DNA levels during ART—offer a unique model to investigate mechanisms underlying reservoir restriction. This study characterizes the genetic features of HIV-1 populations within blood-derived reservoirs of LoViReT individuals. Methods: We sequenced regions of gag , pol , and env genes from 19 LoViReTs and 21 matched ART-treated controls, defined by proviral DNA levels of <100 and >100 HIV-1-DNA copies/10 ⁶ CD4 ⁺ T-cells, respectively. Paired pre-ART samples from 7 LoViReTs and 8 controls were also analyzed. Genetic diversity was assessed using Shannon entropy and intra-quasispecies weighted genetic distance. Phylogenetic analyses and statistical modeling were performed to compare viral populations and explore viral-host associations between groups. Findings: LoViReT individuals exhibited significantly lower intra-host Shannon entropy under ART than controls, with env gene contributing most to this difference. Reconstructed quasispecies haplotypes confirmed reduced viral diversity in LoViReT participants, particularly in env . A subset of LoViReTs also showed increased APOBEC-mediated hypermutation in pol , suggesting greater accumulation of deleterious mutations. Matched pre- and post-ART sequences indicated a similar trend toward reduced diversity before treatment initiation in LoViReTs with increased genetic frequencies of matched HLA-restricted epitopes. Interpretation: These findings indicate that LoViReT individuals maintain a less diverse viral reservoir, potentially reflecting differential immune patterns before therapy and explaining their reduced reservoir size during ART.
SN - 1664-3224
ER -