A Single Dose Study of Pembrolizumab in People With HIV Infection Who are Immunologic Nonresponders.
| Publication Type | Academic Article |
| Authors | Kuruppu J, Purdy J, Pauls C, Rogan D, Blazkova J, Kardava L, Sewack A, Proschan M, Migueles S, Connors M, Webber J, Meeks T, Przygonska P, Adelsberger J, Higgins J, Rupert A, Moir S, Chun T, Lane H, Kovacs J |
| Journal | Open Forum Infect Dis |
| Volume | 13 |
| Issue | 4 |
| Pagination | ofag203 |
| Date Published | 04/03/2026 |
| ISSN | 2328-8957 |
| Abstract | BACKGROUND: Some people with HIV (PWH) have a poor immunologic response to antiretroviral therapy (ART). Such immunologic nonresponders 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. METHOD: 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%-23.5% for CD4+ T cells, and from 45.2% (SD, 9.4%) to 0.1%-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 nonresponders. |
| DOI | 10.1093/ofid/ofag203 |
| PubMed ID | 41983147 |
| PubMed Central ID | PMC13075952 |