A Single Dose Study of Pembrolizumab in People with HIV Infection Who are Immunologic Non-responders

Background Some people with HIV (PWH) have a poor immunologic response to antiretroviral therapy (ART). Such immunologic non-responders are at increased risk for HIV and non-HIV related complications. Immune exhaustion may contribute to poor immune reconstitution, and blockade of PD-1, an immune checkpoint molecule, may thus be beneficial. Methods We undertook a phase 1, 3:1 randomized, placebo-controlled trial of a single 200 mg dose of pembrolizumab in PWH with CD4+ T cell counts between 100 and 350 cells/mm3, who had been on ART and were virally suppressed for at least 12 months. The primary endpoint was the frequency of either Grade 3 or higher adverse events or Grade 2 or higher autoimmune events requiring corticosteroid therapy. Additional endpoints included levels of PD-1 expression, and changes in immune and virologic parameters. Results Of the 7 enrolled participants, 6 received pembrolizumab and 1 received placebo. The only grade 3 event, ophthalmic zoster, developed in the placebo recipient. There were no autoimmune events requiring corticosteroid therapy. CD4+ and CD8+ T cell counts were stable over time, though both showed increased CD38 and HLA-DR expression. PD-1 expression declined from a baseline of 60.4% (SD, 7.4%) to a nadir of 0.8% to 23.5% for CD4+ T cells, and from 45.2% (SD, 9.4%) to 0.1% to 23.2% for CD8+ T cells. There were no significant changes in viral killing, plasma viral loads or proviral DNA levels. Conclusions A single dose of pembrolizumab may be safely administered to PWH who are immunologic non-responders. Clinical Trials Registration ClinicalTrials.gov NCT03367754