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Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting
HIV-1 replicative capacity (RC) provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously publ...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207887/ https://www.ncbi.nlm.nih.gov/pubmed/22072960 http://dx.doi.org/10.1371/journal.ppat.1002321 |
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author | Kouyos, Roger D. von Wyl, Viktor Hinkley, Trevor Petropoulos, Christos J. Haddad, Mojgan Whitcomb, Jeannette M. Böni, Jürg Yerly, Sabine Cellerai, Cristina Klimkait, Thomas Günthard, Huldrych F. Bonhoeffer, Sebastian |
author_facet | Kouyos, Roger D. von Wyl, Viktor Hinkley, Trevor Petropoulos, Christos J. Haddad, Mojgan Whitcomb, Jeannette M. Böni, Jürg Yerly, Sabine Cellerai, Cristina Klimkait, Thomas Günthard, Huldrych F. Bonhoeffer, Sebastian |
author_sort | Kouyos, Roger D. |
collection | PubMed |
description | HIV-1 replicative capacity (RC) provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously published machine-learning tool, which predicts RC values from partial pol sequences with genotypic and clinical data from the Swiss HIV Cohort Study. The machine-learning tool is based on a training set consisting of 65000 RC measurements paired with their corresponding partial pol sequences. We find that predicted RC values (pRCs) correlate significantly with the virus load measured in 2073 infected but drug naïve individuals. Furthermore, we find that, for 53 pairs of sequences, each pair sampled in the same infected individual, the pRC was significantly higher for the sequence sampled later in the infection and that the increase in pRC was also significantly correlated with the increase in plasma viral load and with the length of the time-interval between the sampling points. These findings indicate that selection within a patient favors the evolution of higher replicative capacities and that these in-vitro fitness measures are indicative of in-vivo HIV virus load. |
format | Online Article Text |
id | pubmed-3207887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32078872011-11-09 Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting Kouyos, Roger D. von Wyl, Viktor Hinkley, Trevor Petropoulos, Christos J. Haddad, Mojgan Whitcomb, Jeannette M. Böni, Jürg Yerly, Sabine Cellerai, Cristina Klimkait, Thomas Günthard, Huldrych F. Bonhoeffer, Sebastian PLoS Pathog Research Article HIV-1 replicative capacity (RC) provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously published machine-learning tool, which predicts RC values from partial pol sequences with genotypic and clinical data from the Swiss HIV Cohort Study. The machine-learning tool is based on a training set consisting of 65000 RC measurements paired with their corresponding partial pol sequences. We find that predicted RC values (pRCs) correlate significantly with the virus load measured in 2073 infected but drug naïve individuals. Furthermore, we find that, for 53 pairs of sequences, each pair sampled in the same infected individual, the pRC was significantly higher for the sequence sampled later in the infection and that the increase in pRC was also significantly correlated with the increase in plasma viral load and with the length of the time-interval between the sampling points. These findings indicate that selection within a patient favors the evolution of higher replicative capacities and that these in-vitro fitness measures are indicative of in-vivo HIV virus load. Public Library of Science 2011-11-03 /pmc/articles/PMC3207887/ /pubmed/22072960 http://dx.doi.org/10.1371/journal.ppat.1002321 Text en Kouyos et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kouyos, Roger D. von Wyl, Viktor Hinkley, Trevor Petropoulos, Christos J. Haddad, Mojgan Whitcomb, Jeannette M. Böni, Jürg Yerly, Sabine Cellerai, Cristina Klimkait, Thomas Günthard, Huldrych F. Bonhoeffer, Sebastian Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting |
title | Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting |
title_full | Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting |
title_fullStr | Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting |
title_full_unstemmed | Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting |
title_short | Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting |
title_sort | assessing predicted hiv-1 replicative capacity in a clinical setting |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207887/ https://www.ncbi.nlm.nih.gov/pubmed/22072960 http://dx.doi.org/10.1371/journal.ppat.1002321 |
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