CD30 is preferentially expressed in HIV-infected and viral transcriptionally active CD4 T cells from viremic and ART suppressed individuals. We observed treatment with anti-CD30 antibody drug conjugate, brentuximab vedotin (BV), leads to reduced cell-associated HIV DNA in vitro and transient decreases in cell-associated HIV RNA in vivo. The impact of anti-CD30 therapy on tissue measures of HIV burden is unknown.
Humanized BLT mice were initiated on daily TDF, FTC, and DTG by oral gavage approximately 3 weeks following intraperitoneal infection with HIV-1 JR-CSF. After mice achieved viral suppression they were divided into three treatment cohorts: [1] ART alone control (N=16); [2] ART and 3 intraperitoneal (IP) weekly infusions of 20 mg/kg BV (N=18); [3] ART, BV and a single 2.5/10 μg IP injection of IL15/IL15RaFC given with the first dose of BV (N=18). Three weeks after the last BV infusion, mice were sacrificed and HIV DNA and RNA were isolated from blood, ileocecal junction, spleen, lymph nodes, and liver.
Although the frequency of CD30 expression on human CD4 T cells was low in all cohorts, BV with and without IL15/IL15RaFC led to significant reduction in the frequency of human CD45+CD4+ T cells expressing CD30 (0.09% in ART controls, 0.05% in both treatment cohorts; P=0.03) and HLA-DR (4.0%, 0.6%, 0.6%, respectively; all P<0.01). BV with and without IL15/IL15RaFC also led to the reduced frequency of effector memory CD4 T cells (14% to 8% and 6%, respectively) and increased frequency of naive CD4+ T cells in peripheral blood (68% to 71% and 75%, respectively). Overall, there were no significant changes in blood, spleen, lymph node, and liver levels of cell-associated HIV RNA or DNA, but BV treated mice had significantly lower HIV DNA measured in gut tissue compared with ART-only controls at the time of necropsy (HIV DNA 164 c/10^6 vs 21,788 c/10^6 cells; P=0.04). Gut HIV DNA levels were similar to controls in mice that received concomitant BV and IL15/IL15RaFC.
BV treatment in BLT mice decreased the frequency of CD4 T cells expressing CD30, markers of T cell activation, and effector memory phenotype. BV alone, but not in combination with IL15/IL15RaFC, led to decreased gut HIV DNA levels. However, the high percentage of circulating naive lymphocytes and overall low CD30 expression in the BLT mouse model may have dampened the impact of anti-CD30 therapy on measures of HIV persistence.