Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting

PLoS Pathogens

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