Although its functions are largely undefined, CD30 has been implicated in the activation, proliferation and death of selected cell populations. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Д¬ompeting interests: The authors have declared that no competing interests exist.Д¬D30, a member of the TNF receptor superfamily, is expressed on tumor cells found in Hodgkin and other aggressive lymphomas but only on a very small percentage of lymphocytes in healthy individuals. The work was also supported by the Foundation for AIDS Research (amfAR) Institute for HIV Cure Research. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Дata Availability: All relevant data are within the paper and its Supporting Information files.ДЇunding: This work was supported by Federal funds from NIH/NIAID R21AI116205 (to TJH), UM1 068636 (AIDS Clinical Trials Group Virology Support Laboratory), the Delaney AIDS Research Enterprise (DARE AI096109), (K24 AI069994), the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763), and under Contract no. Received: AugAccepted: JanuPublished: February 22, 2018Д¬opyright: В© 2018 Hogan et al. Douek, Vaccine Research Center, UNITED STATES (2018) Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4 + T cells expressing CD30. These data suggest that CD30 may be a marker of residual, transcriptionally active HIV-1 infected cells in the setting of suppressive ART.Д¬itation: Hogan LE, Vasquez J, Hobbs KS, Hanhauser E, Aguilar-Rodriguez B, Hussien R, et al. Finally, we show through in situ RNA hybridization studies that CD30 and HIV transcriptional activity co-localize in cells from gut biopsies obtained from HIV-1 infected donors. Furthermore, we demonstrate that ex vivo treatment with brentuximab vedotin, an antibody-drug conjugate that targets CD30, reduces the total amount of HIV-1 DNA in PBMC obtained from infected individuals.

These findings were observed in several HIV-1 infected donor groups, regardless of whether or not the participants were receiving suppressive ART.

We demonstrate that cell-associated HIV-1 RNA is highly enriched in CD4 + T cells expressing CD30, a member of the tumor necrosis factor receptor superfamily. Many of these studies, however, were performed prior to the implementation of combination ART, and the relationship between surface CD30 expression, soluble CD30 and HIV-1 infection in ART suppressed individuals, or those with viremic control off ART, is not known. Previous studies have shown that higher levels of soluble CD30 are associated with HIV-1 disease progression. 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. Overall, CD30 may be a marker of residual, transcriptionally active HIV-1 infected cells in the setting of suppressive ART. 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. 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. Using in situ RNA hybridization studies, we show co-localization of CD30 with HIV-1 transcriptional activity in gut-associated lymphoid tissues.

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. 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.

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