Interleukin-2 is a potent latency reversal agent in people with treated HIV-1

Eliciting human immunodeficiency virus type 1 (HIV-1) expression from latently-infected CD4+ T cells allows these rare reservoir cells to become targets of the immune system and may also result in death of reservoir cells via virus-induced cytopathy. We asked whether administration of recombinant interleukin-2 (rIL-2) to people with HIV-1 (PWH) on antiretroviral therapy (ART) would induce HIV-1 replication and activate cellular immunity. Nine men with ART-suppressed HIV-1 completed a single 4-day cycle of rIL-2 administration. Plasma HIV-1 RNA levels rose from <20 copies per milliliter at entry to a mean of 301 copies per milliliter at day 7 (an average increase of 0.82 log10; P=0.008). Additionally, we observed robust natural killer (NK) and T cell activation, with a modest increase in Treg-like cells. Thus, rIL-2 appears to be one of the most potent latency-reversing agents tested in PWH on ART. Overall design: Single-cell RNAseq results (BD AbSeq) from peripheral blood mononuclear cells (PBMCs) acquired at baseline and day 7 from 4 male participants of a clinical trial of recombinant IL-2 administration (aldesleukin; subcutaneous injections of 5 million international units, twice daily, for four consecutive days) (Clinical Trials[dot]gov #NCT03308786).