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AIDS Research and Therapy
Published in: AIDS Research and Therapy 1/2017

Open Access 01-12-2017 | Research

Impaired human immunodeficiency virus type 1 replicative fitness in atypical viremic non-progressor individuals

Authors: Jan Weber, Richard M. Gibson, Lenka Sácká, Dmytro Strunin, Jan Hodek, Jitka Weberová, Marcela Pávová, David J. Alouani, Robert Asaad, Benigno Rodriguez, Michael M. Lederman, Miguel E. Quiñones-Mateu

Published in: AIDS Research and Therapy | Issue 1/2017

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Abstract

Background

Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals—termed viremic non-progressors (VNP) or controllers—do not seem to progress to AIDS, maintaining high CD4+ T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients; however, limited work has been done to characterize viral factors in viremic controllers.

Methods

We analyzed HIV-1 isolates from three VNP individuals and compared the replicative fitness, near full-length HIV-1 genomes and intra-patient HIV-1 genetic diversity with viruses from three typical (TP) and one rapid (RP) progressor individuals.

Results

Viremic non-progressors and typical patients were infected for >10 years (range 10–17 years), with a mean CD4+ T-cell count of 472 cells/mm3 (442–529) and 400 cells/mm3 (126–789), respectively. VNP individuals had a less marked decline in CD4+ cells (mean −0.56, range −0.4 to −0.7 CD4+/month) than TP patients (mean −10.3, −8.2 to −13.1 CD4+/month). Interestingly, VNP individuals carried viruses with impaired replicative fitness, compared to HIV-1 isolates from the TP and RP patients (p < 0.05, 95% CI). Although analyses of the near full-length HIV-1 genomes showed no clear patterns of single-nucleotide polymorphisms (SNP) that could explain the decrease in replicative fitness, both the number of SNPs and HIV-1 population diversity correlated inversely with the replication capacity of the viruses (r = −0.956 and r = −0.878, p < 0.01, respectively).

Conclusion

It is likely that complex multifactorial parameters govern HIV-1 disease progression in each individual, starting with the infecting virus (phenotype, load, and quasispecies diversity) and the intrinsic ability of the host to respond to the infection. Here we analyzed a subset of viremic controller patients and demonstrated that similar to the phenomenon observed in patients with a discordant response to antiretroviral therapy (i.e., high CD4+ cell counts with detectable plasma HIV-1 RNA load), reduced viral replicative fitness seems to be linked to slow disease progression in these antiretroviral-naïve individuals.
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Metadata
Title
Impaired human immunodeficiency virus type 1 replicative fitness in atypical viremic non-progressor individuals
Authors
Jan Weber
Richard M. Gibson
Lenka Sácká
Dmytro Strunin
Jan Hodek
Jitka Weberová
Marcela Pávová
David J. Alouani
Robert Asaad
Benigno Rodriguez
Michael M. Lederman
Miguel E. Quiñones-Mateu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
AIDS Research and Therapy / Issue 1/2017
Electronic ISSN: 1742-6405
DOI
https://doi.org/10.1186/s12981-017-0144-0

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