A Single Dose of Pembrolizumab in HIV-Infected People

A subset of HIV-infected patients, those with poor immunologic response to combined antiretroviral therapy (CD4+ T-cell count of less than 300-350 cells/mm\^3) despite control of viremia, are at increased risk for both HIV-related and non-HIV-related complications compared to immunologic responders. Thus, novel approaches for treating HIV infection are needed to facilitate management of this patient population. One potential drug target for HIV treatment is the T-cell receptor PD-1. Binding of PD-1 to its ligands, PD-L1 and PD-L2, inhibits proliferation of T cells and production of cytokines. This naturally serves to dampen potentially harmful excessive immune responses. Upregulation of PD-1 and/or its ligands can be observed in tumors and people with chronic viral infection, including HIV. This upregulation can inhibit T-cell immune surveillance, which may result in tumor growth or poor control of infection. Pembrolizumab is an IgG4 kappa monoclonal antibody that binds to PD-1, thus blocking the receptor from binding with its ligands. In cancer indications, inhibition of PD-1 induces an antitumor immune response, which in turn reduces tumor growth. The Food and Drug Administration has approved pembrolizumab for treatment of unresectable or metastatic melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, and other cancers. Similarly, in animal models of HIV and in vitro studies, PD-1 blockade was associated with a decrease in viral load and an increase in CD8+ T cells. A clinical trial to examine the effects of PD-1 inhibition by pembrolizumab on HIV infection is thus supported by the data. The purpose of this study is to evaluate, in a randomized, double-blind, placebo-controlled study, the safety and tolerability of a single dose of pembrolizumab in HIV-infected participants who have controlled viremia with a low T-cell count (\> 100 cells/mm3 and less than or equal to 350 cells/mm\^3). Study participants will be followed for 96 weeks after receiving the study drug and will be assessed for adverse events, CD4+ and CD8+ T-cell counts, PD-1 expression, CD8+ T-cell anti-HIV activity, and viral load. If a single dose of pembrolizumab appears to be safe and tolerable, then larger multi-dose and efficacy studies can be planned.