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Emergence of Minor Populations of Human Immunodeficiency Virus Type 1 Carrying the M184V and L90M Mutations in Subjects Undergoing Structured Treatment Interruptions

Metzner, Karin J. ; Bonhoeffer, Sebastian ; Fischer, Marek ; Karanicolas, Rose ; Allers, Kristina ; Joos, Beda ; Weber, Rainer ; Hirschel, Bernard ; G. Kostrikis, Leondios

In: The Journal of Infectious Diseases, 2003, vol. 188, no. 10, p. 1433-1443

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    Titre
    • Emergence of Minor Populations of Human Immunodeficiency Virus Type 1 Carrying the M184V and L90M Mutations in Subjects Undergoing Structured Treatment Interruptions
    Auteur
    • Metzner, Karin J.. Aaron Diamond AIDS Research Center and
    • Bonhoeffer, Sebastian. ETH, Swiss Federal Institute of Technology, Ecology & Evolution and
    • Fischer, Marek. University Hospital Zurich, Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, Zurich, and
    • Karanicolas, Rose. College of Physicians and Surgeons, Columbia University, New York, New York
    • Allers, Kristina. University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, Erlangen, Germany
    • Joos, Beda. University Hospital Zurich, Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, Zurich, and
    • Weber, Rainer. University Hospital Zurich, Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, Zurich, and
    • Hirschel, Bernard. University Hospital of Geneva, Division of Infectious Diseases, Geneva, Switzerland
    • G. Kostrikis, Leondios. University of Athens School of Medicine, Department of Hygiene and Epidemiology, Athens, Greece
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • The Journal of Infectious Diseases, 2003, vol. 188, no. 10, p. 1433-1443. The University of Chicago Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:299629
    Summary
    The use of structured treatment interruption (STI) in human immunodeficiency virus (HIV)-infected subjects is currently being studied as an alternative therapeutic strategy for HIV-1. The potential risk for selection of drug-resistant HIV-1 variants during STI is unknown and remains a concern. Therefore, the emergence of drug resistance in sequential plasma samples obtained from 28 subjects with chronic HIV infection was studied. They underwent 4 cycles of 2-week STI, followed by 8-week retreatment with highly active antiretroviral therapy identical to that used before STI, and they had never failed treatment before undergoing STI. At week 40, treatment was stopped for a longer period. Minor populations of drug-resistant variants were detected by quantitative real-time polymerase chain reaction, by use of allele-discriminating oligonucleotides for 2 key resistance mutations: L90M (protease) and M184V (reverse transcriptase). The approximate discriminative power was 0.1%. In 14 of 25 and in 3 of 25 subjects, the M184V and the L90M mutations, respectively, were detected as minor populations, at different times during STI. Overall, these results indicate that, in subjects undergoing multiple STIs, HIV-1 variants carrying drug-resistance mutations can emerge during periods of increased HIV-1 replication