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Assessing predicted HIV-1 replicative capacity in a clinical setting
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 1194613
Author(s) Kouyos, R. D.; von Wyl, V.; Hinkley, T.; Petropoulos, C. J.; Haddad, M.; Whitcomb, J. M.; Boni, J.; Yerly, S.; Cellerai, C.; Klimkait, T.; Gunthard, H. F.; Bonhoeffer, S.; Swiss HIV Cohort Study,
Author(s) at UniBasel Klimkait, Thomas
Year 2011
Title Assessing predicted HIV-1 replicative capacity in a clinical setting
Journal PLoS Pathogens
Volume 7
Number 11
Pages / Article-Number e1002321
Keywords virus type-1 fitness; disease progression; drug-resistance; viral load; reverse-transcriptase; set-point; ex-vivo; infection; diversity; mutations
Abstract 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.
Publisher Public Library of Science
ISSN/ISBN 1553-7366 ; 1553-7374
edoc-URL http://edoc.unibas.ch/dok/A6004822
Full Text on edoc No
Digital Object Identifier DOI 10.1371/journal.ppat.1002321
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/22072960
ISI-Number WOS:000297337300005
Document type (ISI) Journal Article
 
   

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