a, AZD5582 (0.1 mg kg−1) was administered to healthy rhesus macaques (n = 3) by intravenous infusion. Plasma concentrations of AZD5582 (left y axis) are shown for the indicated time points. Flow cytometry was used to measure intracellular p100 levels, shown as the geometric mean fluorescence intensity (gMFI) in CD4+ T cells and plotted as the percentage of baseline of p100 gMFI (right y axis). b, Plasma concentrations of AZD5582 after one (dark red), three (red), six (pink) or ten (orange) doses in six SIV-infected ART-treated rhesus macaques (RM) and after one dose in three uninfected control rhesus macaques (grey). Individual values are shown as symbols. c, Western blot analyses of inactive p100 and active p52 forms of NF-κB2 in lymph-node mononuclear cells collected 48 h after the third or tenth dose of AZD5582 in SIV-infected ART-suppressed rhesus macaques (red; n = 3 for both the 3-dose and 10-dose groups) or at equivalent time points for placebo controls (blue; n = 2 for both the 3-dose and 10-dose groups). Immunoblots are shown in the top panels and densitometry analyses of the p52:p100 ratios are shown in the bottom panels. The line represents the median. d, Cryopreserved control rhesus macaque splenocytes were treated with the indicated concentrations of AZD5582 for 48 h, then p100/p52 levels were analysed by western blotting to measure engagement of the ncNF-κB pathway. e, DMSO-normalized densitometric p52:p100 ratio versus the AZD5582 concentration. For d, e, the experiments were performed in duplicate. f, Cryopreserved rhesus macaque splenocytes were exposed to DMSO alone (Untx), 100 nM AZD5582 washed off after 1 h and cultured for 47 h (Pulsed) or continuous 100 nM AZD5582 for 48 h (Cont.), after which the cells were studied by western blot for p100 and p52 levels. g, Densitometric p52:p100 ratio. For f, g, data represent a single experiment. For gel source data, see Supplementary Fig. 1. Source data