HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy.
BACKGROUND:The clinical significance and cellular sources of residual human immunodeficiency virus type 1 (HIV-1) production despite suppressive combination antiretroviral therapy (cART) remain unclear and the effect of low-level viremia on T-cell homeostasis is still debated. METHODOLOGY/PRINCIPAL...
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doaj-ea9a16013d54495caaf29faf1aaed5802020-11-25T02:10:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-10-01410e765810.1371/journal.pone.0007658HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy.Maud MavignerPierre DelobelMichelle CazabatMartine DuboisFatima-Ezzahra L'faqihi-OliveStéphanie RaymondChristophe PasquierBruno MarchouPatrice MassipJacques IzopetBACKGROUND:The clinical significance and cellular sources of residual human immunodeficiency virus type 1 (HIV-1) production despite suppressive combination antiretroviral therapy (cART) remain unclear and the effect of low-level viremia on T-cell homeostasis is still debated. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the recently produced residual viruses in the plasma and short-lived blood monocytes of 23 patients with various immunological responses to sustained suppressive cART. We quantified the residual HIV-1 in the plasma below 50 copies/ml, and in the CD14(high) CD16(-) and CD16+ monocyte subsets sorted by flow cytometry, and predicted coreceptor usage by genotyping V3 env sequences. We detected residual viremia in the plasma of 8 of 10 patients with poor CD4+ T-cell reconstitution in response to cART and in only 5 of 13 patients with good CD4+ T-cell reconstitution. CXCR4-using viruses were frequent among the recently produced viruses in the plasma and in the main CD14(high) CD16(-) monocyte subset. Finally, the residual viremia was correlated with persistent CD4+ and CD8+ T-cell activation in patients with poor immune reconstitution. CONCLUSIONS:Low-level viremia could result from the release of archived viruses from cellular reservoirs and/or from ongoing virus replication in some patients. The compartmentalization of the viruses between the plasma and the blood monocytes suggests at least two origins of residual virus production during effective cART. CXCR4-using viruses might be produced preferentially in patients on cART. Our results also suggest that low-level HIV-1 production in some patients may contribute to persistent immune dysfunction despite cART.http://europepmc.org/articles/PMC2765414?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maud Mavigner Pierre Delobel Michelle Cazabat Martine Dubois Fatima-Ezzahra L'faqihi-Olive Stéphanie Raymond Christophe Pasquier Bruno Marchou Patrice Massip Jacques Izopet |
spellingShingle |
Maud Mavigner Pierre Delobel Michelle Cazabat Martine Dubois Fatima-Ezzahra L'faqihi-Olive Stéphanie Raymond Christophe Pasquier Bruno Marchou Patrice Massip Jacques Izopet HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. PLoS ONE |
author_facet |
Maud Mavigner Pierre Delobel Michelle Cazabat Martine Dubois Fatima-Ezzahra L'faqihi-Olive Stéphanie Raymond Christophe Pasquier Bruno Marchou Patrice Massip Jacques Izopet |
author_sort |
Maud Mavigner |
title |
HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. |
title_short |
HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. |
title_full |
HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. |
title_fullStr |
HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. |
title_full_unstemmed |
HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. |
title_sort |
hiv-1 residual viremia correlates with persistent t-cell activation in poor immunological responders to combination antiretroviral therapy. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2009-10-01 |
description |
BACKGROUND:The clinical significance and cellular sources of residual human immunodeficiency virus type 1 (HIV-1) production despite suppressive combination antiretroviral therapy (cART) remain unclear and the effect of low-level viremia on T-cell homeostasis is still debated. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the recently produced residual viruses in the plasma and short-lived blood monocytes of 23 patients with various immunological responses to sustained suppressive cART. We quantified the residual HIV-1 in the plasma below 50 copies/ml, and in the CD14(high) CD16(-) and CD16+ monocyte subsets sorted by flow cytometry, and predicted coreceptor usage by genotyping V3 env sequences. We detected residual viremia in the plasma of 8 of 10 patients with poor CD4+ T-cell reconstitution in response to cART and in only 5 of 13 patients with good CD4+ T-cell reconstitution. CXCR4-using viruses were frequent among the recently produced viruses in the plasma and in the main CD14(high) CD16(-) monocyte subset. Finally, the residual viremia was correlated with persistent CD4+ and CD8+ T-cell activation in patients with poor immune reconstitution. CONCLUSIONS:Low-level viremia could result from the release of archived viruses from cellular reservoirs and/or from ongoing virus replication in some patients. The compartmentalization of the viruses between the plasma and the blood monocytes suggests at least two origins of residual virus production during effective cART. CXCR4-using viruses might be produced preferentially in patients on cART. Our results also suggest that low-level HIV-1 production in some patients may contribute to persistent immune dysfunction despite cART. |
url |
http://europepmc.org/articles/PMC2765414?pdf=render |
work_keys_str_mv |
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