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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
HIV rebounds from latently infected cells, rather than from continuing low-level replication
Proceedings of the National Academy of Sciences of the United States of America, Volume 105, No. 43, Year 2008
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Description
Rapid rebound of plasma viremia in patients after interruption of long-term combination antiretroviral therapy (cART) suggests persistence of low-level replicating cells or rapid reactivation of latently infected cells. To further characterize rebounding virus, we performed extensive longitudinal clonal evolutionary studies of HIV env C2-V3-C3 regions and exploited the temporal relationships of rebounding plasma viruses with regard to pretreatment sequences in 20 chronically HIV-1-infected patients having undergone multiple 2-week structured treatment interruptions (STI). Rebounding virus during the short STI was homogeneous, suggesting mono- or oligoclonal origin during reactivation. No evidence for a temporal structure of rebounding virus in regard to pretreatment sequences was found. Furthermore, expansion of distinct lineages at different STI cycles emerged. Together, these findings imply stochastic reactivation of different clones from long-lived latently infected cells rather than expansion of viral populations replicating at low levels. After treatment was stopped, diversity increased steadily, but pretreatment diversity was, on average, achieved only >2.5 years after the start of STI when marked divergence from preexisting quasispecies also emerged. In summary, our results argue against persistence of ongoing lowlevel replication in patients on suppressive cART. Furthermore, a prolonged delay in restoration of pretreatment viral diversity after treatment interruption demonstrates a surprisingly sustained evolutionary bottleneck induced by punctuated antiretroviral therapy. © 2008 by The National Academy of Sciences of the USA.
Authors & Co-Authors
Fischer, Marek
Switzerland, Zurich
Universitatsspital Zurich
Pillai, Satish K.
United States
Va Medical Center
Wong, Joseph K.
United States
Va Medical Center
Böni, Jürg
Switzerland, Zurich
Universität Zürich
Hirschel, B. J.
Switzerland, Geneva
Hôpitaux Universitaires de Genève
Trkola, Alexandra
Switzerland, Zurich
Universitatsspital Zurich
Günthard, Huldrych F.
Switzerland, Zurich
Universitatsspital Zurich
Battegay, Manuel
Switzerland, Basel
Universitätsspital Basel
Bernasconi, Enos
Unknown Affiliation
Böni, Jürg
Unknown Affiliation
Bucher, Heiner C.
Switzerland, Basel
Universitätsspital Basel
Bürgisser, Ph
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Cattacin, Sandro
Switzerland, Geneva
Université de Genève
Cavassini, Matthias L.
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Dubs, Rolf W.
Switzerland, Zurich
Universitatsspital Zurich
Egger, Matthias
Switzerland, Bern
University of Bern
Elzi, Luigia
Switzerland, Basel
Universitätsspital Basel
Flepp, Markus J.
Switzerland, Zurich
Universitatsspital Zurich
Fontana, Adriano
Switzerland, Zurich
Universitatsspital Zurich
Francioli, Patrick B.
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Furrer, Hansjakob
Switzerland, Bern
University of Bern
Fux, Christoph Andreas
Switzerland, Bern
University of Bern
Gorgievski, Meri
Switzerland, Bern
University of Bern
Günthard, Hüldrych Fritz
Switzerland, Zurich
Universitatsspital Zurich
Hirsch, Hans H.
Switzerland, Basel
Universitat Basel
Hirschel, Bernard J.
Switzerland, Geneva
University Hospital
Hösli, Irene Mathilde
Switzerland, Basel
Universitätsspital Basel
Kahlert, Christian R.
Switzerland, St Gallen
Kantonsspital St.gallen
Kaiser, Laurent K.
Switzerland, Geneva
University Hospital
Karrer, Urs
Switzerland, Zurich
Universitatsspital Zurich
Kind, Christian H.
Unknown Affiliation
Klimkait, Thomas
Switzerland, Basel
Universitat Basel
Ledergerber, Bruno
Switzerland, Zurich
Universitatsspital Zurich
Martinez, Begogna
Switzerland, Geneva
University Hospital
Müller, Nicolas J.
Switzerland, Zurich
Universitatsspital Zurich
Nadal, David
Switzerland, Zurich
Kinderspital Zürich
Paccaud, Fred Michel
Switzerland, Lausanne
Université de Lausanne Unil
Pantaleo, Giuseppe P.
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Rauch, Andri
Switzerland, Bern
University of Bern
Regenass, Stephan
Switzerland, Zurich
Universitatsspital Zurich
Rickenbach, Martin
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Rudin, Christoph
Switzerland, Basel
Universitäts-kinderspital Beider Basel
Schmid, Patrick
Switzerland, St Gallen
Kantonsspital St.gallen
Schültze, Detlev
Unknown Affiliation
Schüpbach, Jörg Rg
Unknown Affiliation
Speck, Roberto F.
Switzerland, Zurich
Universitatsspital Zurich
Taffé, Patrick
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Telenti, Amalio
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Trkola, Alexandra
Switzerland, Zurich
Universitatsspital Zurich
Vernazza, Pietro Luigi
Switzerland, St Gallen
Kantonsspital St.gallen
Weber, Rainer
Switzerland, Zurich
Universitatsspital Zurich
Yerly, Sabine T.B.D.
Switzerland, Geneva
University Hospital
Statistics
Citations: 298
Authors: 52
Affiliations: 15
Identifiers
Doi:
10.1073/pnas.0804192105
ISSN:
10916490
Research Areas
Infectious Diseases
Sexual And Reproductive Health
Study Design
Cohort Study