BACKGROUND: Alemtuzumab (ATM) is a lymphocyte-depleting humanized anti-CD52 monoclonal antibody used for the treatment of multiple malignancies and licensed for relapsing-remitting multiple sclerosis. Here, we evaluated whether ATM can deplete long-lived latently infected CD4+ memory T cells in SIV-infected rhesus macaques (RM) on suppressive combination antiretroviral therapy (cART). We hypothesized that ATM-induced depletion and reconstitution in the presence of cART may significantly reduce SIV persistence.
METHODS: RM were initially screened for CD52 expression on erythrocytes using an agglutination assay to minimize any risk of hemolysis. Nine RM were intravenously inoculated with SIVmac239 and after 12 days received cART (tenofovir/emtricitabine/dolutegravir). Once sustained virus suppression (<15 RNA copies/ml) was achieved, 6 RM received intravenous doses of ATM at 5mg/Kg on days 0, 7, 14 and 29. Three RM did not receive ATM (controls). Lymph node (LN) and gastrointestinal tract (GIT) tissue was collected at 10 and 20 weeks. SIV DNA and RNA were quantified by qPCR/qRT-PCR and markers of immune activation by flow cytometry
CONCLUSION: ATM can significantly reduce total circulating CD4 + T-cells but only minimally reduces SIV DNA levels in the PBMC of SIV-infected RM on cART. The minimal effect on SIV DNA in LN and GIT suggests either limited depletion of resident memory T-cells in those tissues or a rapid reconstitution at those sites, perhaps by expanded clones. Clearance of infection in one animal, with a low pre ART viral burden, was observed and warrants further investigation.