Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30.

PLoS Pathogens
Louise E HoganTimothy J Henrich

Abstract

HIV-1-infected cells persist indefinitely despite the use of combination antiretroviral therapy (ART), and novel therapeutic strategies to target and purge residual infected cells in individuals on ART are urgently needed. Here, we demonstrate that CD4+ T cell-associated HIV-1 RNA is often highly enriched in cells expressing CD30, and that cells expressing this marker considerably contribute to the total pool of transcriptionally active CD4+ lymphocytes in individuals on suppressive ART. Using in situ RNA hybridization studies, we show co-localization of CD30 with HIV-1 transcriptional activity in gut-associated lymphoid tissues. We also demonstrate that ex vivo treatment with brentuximab vedotin, an antibody-drug conjugate (ADC) that targets CD30, significantly reduces the total amount of HIV-1 DNA in peripheral blood mononuclear cells obtained from infected, ART-suppressed individuals. Finally, we observed that an HIV-1-infected individual, who received repeated brentuximab vedotin infusions for lymphoma, had no detectable virus in peripheral blood mononuclear cells. Overall, CD30 may be a marker of residual, transcriptionally active HIV-1 infected cells in the setting of suppressive ART. Given that CD30 is only expressed on ...Continue Reading

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Citations

May 31, 2018·Current Opinion in HIV and AIDS·Timothée Bruel, Olivier Schwartz
Mar 6, 2019·Current HIV/AIDS Reports·Brooks I MitchellLishomwa C Ndhlovu
Aug 20, 2019·Nature Communications·Carla Serra-PeinadoMaria J Buzon
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Sep 18, 2021·Frontiers in Immunology·Lesley R de ArmasSavita Pahwa

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Methods Mentioned

BETA
fluorescence activated cell sorting
PCR
blood draws
biopsy
fluoresce activated cell sorting
ELISA
fluorescence-activated cell sorting
activated cell sorting

Software Mentioned

TreeStar
FlowJo

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