Background: We previously reported that CD4+ T-cells expressing the tumor marker, CD30, were enriched in HIV RNA, and that CD30 mRNA and HIV RNA colocalized in gut tissue from ART suppressed individuals. Ex vivo treatment of PBMC from ART-suppressed individuals with the anti-CD30 antibody-drug conjugate, brentuximab vedotin, led to a significant decrease in HIV DNA levels. However, the direct, longitudinal impact of bretuximab vedotin therapy on HIV persistence in vivo is not known. We studied the impact of brentuximab vedotin therapy for Hodgkin lymphoma on HIV persistence in a newly identified HIV-infected individual on ART
Methods: In depth characterization of CD4+ T cell-associated HIV-1 unspliced RNA and total DNA, and immune phenotyping of CD30 expression on PBMC were determined prior to and 3 weeks following brentuximab vedotin therapy in an HIV-infected individual.
Results: The male participant was on long-term suppressive ART and was diagnosed with stage IV Hodgkin lymphoma in 2014. He received doxorubicin/bleomycin/vinblastine/dacarbazine therapy and went into complete remission. In 2017 he was treated with salvage chemotherapy (ifosfamide/carboplatin/etoposide) for recurrence, and again went into remission. Brentuximab vedotin was started as bridging therapy prior to planned autologous hematopoietic stem cell transplant. Prior to brentuximab vedotin, CD4+ T-cell-associated HIV RNA and DNA levels were 7,359 and 58 copies/10^6 CD4+ T-cells, respectively. Three-weeks following a single 1.8 mg/kg dose, no HIV RNA could be detected in CD4+T-cells (>3-log₁₀ reduction), and total cell-associated HIV DNA levels decreased by 42% (Figure). A concomitant 4-fold decrease in the frequency of CD4+ T-cells expressing CD30 was observed (2.26% to 0.54%).
Conclusions: A single dose of the anti-CD30 antibody-drug conjugate, brentuximab vedotin reduced the number of circulating CD30+CD4+ T cells and led to a major decrease in circulating cell-associated HIV RNA and a modest reduction in total cell-associated HIV DNA. These data and our prior observation of the loss of HIV DNA and RNA following multi-cycle brentuximab vedotin therapy suggest that targeting CD30 may reduce the pool of transcriptionally active HIV-infected cells that persist on suppressive ART. Longitudinal sampling of blood and tissues is underway to determine the longer-term effect of anti-CD30 therapy on the total HIV reservoir.



[Reduction in Cell-Associated HIV RNA and DNA Following Single Dose Brentuximab Vedotin Anti-CD30 Antibody-Drug Conjugate (ADC)Therapy]