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...

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Autores principales:	Roger D Kouyos, Viktor von Wyl, Trevor Hinkley, Christos J Petropoulos, Mojgan Haddad, Jeannette M Whitcomb, Jürg Böni, Sabine Yerly, Cristina Cellerai, Thomas Klimkait, Huldrych F Günthard, Sebastian Bonhoeffer, Swiss HIV Cohort Study
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ac5e331eaef14db0a87440f062c39d55
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spelling	oai:doaj.org-article:ac5e331eaef14db0a87440f062c39d552021-11-18T06:05:09ZAssessing predicted HIV-1 replicative capacity in a clinical setting.1553-73661553-737410.1371/journal.ppat.1002321https://doaj.org/article/ac5e331eaef14db0a87440f062c39d552011-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22072960/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374HIV-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.Roger D KouyosViktor von WylTrevor HinkleyChristos J PetropoulosMojgan HaddadJeannette M WhitcombJürg BöniSabine YerlyCristina CelleraiThomas KlimkaitHuldrych F GünthardSebastian BonhoefferSwiss HIV Cohort StudyPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 11, p e1002321 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Roger D Kouyos Viktor von Wyl Trevor Hinkley Christos J Petropoulos Mojgan Haddad Jeannette M Whitcomb Jürg Böni Sabine Yerly Cristina Cellerai Thomas Klimkait Huldrych F Günthard Sebastian Bonhoeffer Swiss HIV Cohort Study Assessing predicted HIV-1 replicative capacity in a clinical setting.
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	article
author	Roger D Kouyos Viktor von Wyl Trevor Hinkley Christos J Petropoulos Mojgan Haddad Jeannette M Whitcomb Jürg Böni Sabine Yerly Cristina Cellerai Thomas Klimkait Huldrych F Günthard Sebastian Bonhoeffer Swiss HIV Cohort Study
author_facet	Roger D Kouyos Viktor von Wyl Trevor Hinkley Christos J Petropoulos Mojgan Haddad Jeannette M Whitcomb Jürg Böni Sabine Yerly Cristina Cellerai Thomas Klimkait Huldrych F Günthard Sebastian Bonhoeffer Swiss HIV Cohort Study
author_sort	Roger D Kouyos
title	Assessing predicted HIV-1 replicative capacity in a clinical setting.
title_short	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_sort	assessing predicted hiv-1 replicative capacity in a clinical setting.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/ac5e331eaef14db0a87440f062c39d55
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Assessing predicted HIV-1 replicative capacity in a clinical setting.

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