Journal Article

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

Thanh, Cassandra, Sanjabi, Shomyseh, Trapecar, Martin, Deeks, Steven G., Hogan, Louise E., Smith, Louis C. B., Khan, Shahzada, Aguilar-Rodriguez, Brandon, Hussien, Rajaa, Kuritzkes, Daniel R., Gibson, Erica A., Vasquez, Joshua, Carvidi, Alexander B., Hobbs, Kristen S., Somsouk, Ma, Stoddart, Cheryl A., Hanhauser, Emily, Henrich, Timothy J.

2018

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Anti-HIV Agents - pharmacology / Antiretroviral agents / Antiretroviral drugs / Antiretroviral therapy / Antiretroviral Therapy, Highly Active / Biology and Life Sciences / Biomarkers - blood / Biomarkers - metabolism / Blood / Brentuximab Vedotin / CD30 antigen / CD4 antigen / CD4 Lymphocyte Count / CD4-Positive T-Lymphocytes - drug effects / CD4-Positive T-Lymphocytes - metabolism / CD4-Positive T-Lymphocytes - pathology / CD4-Positive T-Lymphocytes - virology / Cells, Cultured / Cohort Studies / Deoxyribonucleic acid / DNA / DNA, Viral - blood / DNA, Viral - metabolism / Drug therapy / Gene expression / Gut-associated lymphoid tissues / HIV / HIV Infections - drug therapy / HIV Infections - metabolism / HIV Infections - pathology / HIV Infections - virology / HIV-1 - drug effects / HIV-1 - isolation & purification / HIV-1 - pathogenicity / HIV-1 - physiology / Human immunodeficiency virus / Humans / Hybridization / Immunoconjugates - pharmacology / Immunology / In Situ Hybridization / Ki-1 Antigen - antagonists & inhibitors / Ki-1 Antigen - blood / Ki-1 Antigen - chemistry / Ki-1 Antigen - metabolism / Leukocytes (mononuclear) / Localization / Lymphocytes / Lymphocytes T / Lymphoid tissue / Lymphoid Tissue - drug effects / Lymphoid Tissue - metabolism / Lymphoid Tissue - pathology / Lymphoid Tissue - virology / Lymphoma / Medicine / Medicine and Health Sciences / Monoclonal antibodies / Peripheral blood mononuclear cells / Rectum - drug effects / Rectum - metabolism / Rectum - pathology / Rectum - virology / Research and Analysis Methods / Ribonucleic acid / RNA / RNA, Viral - blood / RNA, Viral - metabolism / Solubility / Supervision / Targeted cancer therapy / Therapeutic applications / Tissues / Transcription / Transcriptional Activation - drug effects / Viral Load - drug effects / Virology / Viruses