PLoS Pathogens | |
Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting | |
Thomas Klimkait1  Sebastian Bonhoeffer2  Trevor Hinkley2  Roger D. Kouyos3  Christos J. Petropoulos3  the Swiss HIV Cohort Study3  Huldrych F. Günthard4  Cristina Cellerai5  Jeannette M. Whitcomb6  Jürg Böni6  Mojgan Haddad6  Viktor von Wyl7  Sabine Yerly8  | |
[1] Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland;Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland;ETH Zürich, Institute of Integrative Biology, Zürich, Switzerland;Institute of Medical Microbiology, Department Biomedicine, University of Basel, Basel, Switzerland;Laboratory of Virology and AIDS Center, Geneva University Hospital, Geneva, Switzerland;Monogram Biosciences, South San Francisco, California, United States of America;Princeton University, Department of Ecology and Evolutionary Biology, Princeton, New Jersey, United States of America;Swiss National Center for Retroviruses, Institute of Medical Virology, University of Zurich | |
关键词: HIV; Viral replication; RNA viruses; Viral load; Antimicrobial resistance; Cohort studies; Linear regression analysis; HIV-1; | |
DOI : 10.1371/journal.ppat.1002321 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
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RO201902017273629ZK.pdf | 268KB | download |