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

Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30.
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Hogan LE, Vasquez J, Hobbs KS, Hanhauser E, Aguilar-Rodriguez B, Hussien R, Thanh C, Gibson EA, Carvidi AB, Smith LCB, Khan S, Trapecar M, Sanjabi S, Somsouk M, Stoddart CA, Kuritzkes DR, Deeks SG, Henrich TJ,


Hogan LE, Vasquez J, Hobbs KS, Hanhauser E, Aguilar-Rodriguez B, Hussien R, Thanh C, Gibson EA, Carvidi AB, Smith LCB, Khan S, Trapecar M, Sanjabi S, Somsouk M, Stoddart CA, Kuritzkes DR, Deeks SG, Henrich TJ, (click to view)

Hogan LE, Vasquez J, Hobbs KS, Hanhauser E, Aguilar-Rodriguez B, Hussien R, Thanh C, Gibson EA, Carvidi AB, Smith LCB, Khan S, Trapecar M, Sanjabi S, Somsouk M, Stoddart CA, Kuritzkes DR, Deeks SG, Henrich TJ,

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PLoS pathogens 2018 02 2214(2) e1006856 doi 10.1371/journal.ppat.1006856

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 a small number of total mononuclear cells, it is a potential therapeutic target of persistent HIV-1 infection.

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