Background
We conducted a Phase 2, open-label study to evaluate the safety of N-803 with ART in acute HIV infection (AHI) and evaluated the impact on HIV viral load (VL), levels of vDNA and vRNA in CD4 T cells and lymph nodes (LN).
Methods
We randomized 12 participants in AHI to receive immediate ART (n=4, Fiebig 1-2) or ART + N-803 (n=8, Fiebig 1-4) at 6 mcg/kg SC abdominally at weeks 0, 3, and 6 then followed to week 12. All participants had inguinal LN biopsy at wk 0 and week 6.5. Blood was drawn for VL, CD4 and CD8 count. Adverse events (AEs) were solicited every N-803 injection. CD4 T cells and LN vRNA and vDNA were compared using nonparametric Wilcoxon signed rank, Mann-Whitney U and Kruskal-Wallis tests and Spearman correlations.
Results
Median (IQR) age was 32(26-35) years in the N-803 arm, 24(21-28) years in the controls. All N-803 recipients reported injection site redness at all time-points (n=24) with 4 mild, 3 moderate and 17 severe. For injection site swelling (n=23), 6 were mild, 9 moderate and 8 severe. Despite this, injection site AEs resolved in 7 days and all participants consented to continued N-803 administration.
There was no significant difference at baseline for CD4 (300 vs 548 cells/mm3), HIV VL (6.15 vs 5.73 log10) and CD4 count increase over time between groups. While VL were overall comparable across groups, VL significantly declined (p=0.008) after the first dose of N-803 compared to ART-only (FigA).
vRNA and vDNA were obtained from CD4 T cells and LN from 7 ART + N-803 participants and 4 ART participants. vRNA (LTR-Gag, Tat-Rev) and vDNA (total, integrated, 2-LTR circles) levels declined for all participants in CD4 T cells in 12 weeks and LN in 6.5 weeks. There was no significant difference in the decline of vRNA and vDNA between groups for LN (adjusted p≥0.545) and CD4 T cells (adjusted p≥0.218) from baseline (FigB).
Conclusions
N-803 with ART was safe and resulted in a rapid plasma HIV VL decline from study baseline compared to ART alone. While there was some evidence of a faster decline in viremia immediately post N-803 injection, differences in reservoir measurements were overwhelmed by the large fluctuations that occur over the first weeks of ART in acute infection, inter-host variability, and the small number of participants. To further explore the impact of N-803 on viral reservoirs, all eligible and consenting study participants will receive an additional single dose of N-803 followed by ATI until HIV viral load >1,000 copies/ml for a maximum of 4 weeks.