Background
N-803, a clinically licensed IL-15 receptor superagonist, is safe in humans and showed potential for HIV remission in non-human primates. We evaluated the safety and impact on HIV reservoir of N-803 administered during acute HIV infection (AHI) in combination with ART in a Phase 2, open-label study, followed by evaluating the impact of N-803 on HIV remission through an analytic treatment interruption (ATI).
Methods
RV550 is a 3-step clinical trial that enrolled participants in AHI. In Step 1, participants received ART alone or ART + N-803 (6 mcg/kg every 3 weeks for 3 doses). Whole lymph node biopsies were obtained at baseline and two weeks post final N-803 administration during Step 1. Step 2 added one dose of N-803 regardless of randomization, followed by ATI with weekly HIV viral load (VL) rebound monitoring up to 12 weeks. VL restart criteria were ≥1,000 copies/ml for 4 weeks or confirmed ≥100,000 copies/ml. Step 3 monitored viral re-suppression on ART.
Endpoints for Step 1 included safety, vDNA/vRNA in blood and lymph node (LN) tissue, reservoir analyses, and quantification of vRNA in LN. Endpoints in Step 2 included ATI time to VL > 1,000 copies/ml plus VL AUC during 4 weeks thereafter. HIV re-suppression was assessed in Step 3.
Results
Twelve participants completed Step 1 of whom 7 consented to continue to Step 2 ATI. No difference in age, sex, Fiebig stage, CD4 or CD8 between groups at either entry into Step 1 or Step 2.
As previously reported, N-803 injection site reactions resolved within 7 days. No ATI-related adverse events or discontinuations were observed. N-803 + ART resulted in a faster VL decline compared to ART alone, but no difference in vDNA in blood.
Additional LN tissue analysis now demonstrates a non-significant 50-fold decrease in vRNA in the N-803 group (Fig.1A).
In Step 2, median ATI duration was 45 (32-69) days. There were no significant differences between groups in time to viral rebound, peak viral load, or time to ART re-initiation (Fig.1B) nor in time to viral re-suppression in Step 3. Median time to viral re-suppression was 45 (26-82) days.
Conclusions
N-803 was safe and did not significantly alter viral rebound kinetics during ATI. Although a trend toward reduced HIV reservoir size in LN was observed, N-803 alone was insufficient to achieve sustained remission. These findings support further investigation of N-803 in combination strategies.
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