PD-1 expression on T cells is associated with cellular exhaustion in HIV. We evaluated multiple immunologic parameters following infusion of cemiplimab, an anti-PD1 monoclonal antibody, in ART-suppressed persons with HIV (PWH) in ACTG A5370.
Using flow cytometry, we evaluated changes in CD4+ and CD8+ T cell polyfunctional responses (?2) to HIV peptide pools by measuring intracellular expression of CD107a, IFN?, TNF?, and/or IL-2 at baseline and at set timepoints post-infusion of cemiplimab. Concurrently, we determined frequencies of T cells expressing PD1 and other inhibitory receptors (IR): CTLA4, TIM3, TIGIT, LAG3, and PDL1. Residual viremia was measured using a single copy assay.
Four participants received 0.3mg/kg cemiplimab infusions; two at week 0 only due to immune related adverse events (irAE) and two at weeks 0 and 6. Enrollment was stopped due to one probable Gr 2 thyroiditis and one possible hepatic irAE. PD-1 receptor occupancy remained >70% 4 to 8 weeks after the last dose. Among four participants who received ? 1 dose of cemiplimab, the percentage of gag-specific polyfunctional CD8+ T cells increased 2.2-fold from baseline to post-infusion timepoints (mean of weeks 2 to 12); percentage of gag-specific polyfunctional CD4+ T cells increased 1.8-fold. One participant who received 2 doses had a +6.2-fold and +3.4-fold change in CD8+ and CD4+ polyfunctional T cells to weeks 2-12, respectively (red line in Figure). Increased CD8+ and CD4+ T cell polyfunctional responses persisted through week 28. In this participant, residual viremia increased from 2.5 cps/mL (baseline) to 4.3 (week 6) and 8.1 (week 12). Baseline median frequencies of CD4+ and CD8+ PD-1+ T cells for the 4 participants were 3.4% and 6.7%. The participant with immunologic responses and residual viremia had baseline percentages of PD1+ CD4+ and CD8+ T cells of 7.1% and 7.3%, respectively. Post-infusion, percentages of CD4+ and CD8+ T cells expressing ?2 IRs in this participant were similar or lower than baseline.
We observed a possible immunologic response in 1 of 4 participants who received at least one dose of 0.3 mg/kg cemiplimab. The responding participant had the highest percentage of CD4+ T cells expressing PD1 at baseline and an increase in residual viremia post-infusion which may indicate immunologic and virologic responses following IR-blockade therapy among PWH. The benefits of this therapeutic strategy for HIV remission should be weighed against the potential for irAE. ?