The impact of immune checkpoint therapy on the latent reservoir in HIV infected individuals with cancer on antiretroviral therapy.

Abstract

OBJECTIVE\nTo quantify HIV specific immunological and virological changes in people living with HIV (PLWH) on antiretroviral therapy (ART) with malignancy who received immune checkpoint blockade (ICB).\n\n\nDESIGN\nObservational cohort study.\n\n\nMETHODS\nBlood samples were collected before and after four cycles of ICB in HIV positive adults on ART. Virological assessments performed on CD4+ T cells included: cell associated (CA) unspliced (US) HIV RNA, cell associated (CA) HIV DNA, Tat/rev Induced Limiting Dilution Assay (TILDA), and plasma HIV RNA using a single copy assay (SCA). Flow cytometry was used to assess the frequency of precursor exhausted T cells (Tpex) and exhausted T cells (Tex), and Gag-specific CD4+ and CD8+ T cells positive for IFN-γ, TNF-α, or CD107a by intracellular cytokine staining (ICS).\n\n\nRESULTS\nParticipant (P)1 received avelumab (anti-PD-L1) for Merkel cell carcinoma. P2 and P3 received ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) for metastatic melanoma.An increase in CA-US RNA following each infusion was noted in all 3 participants. There were no consistent changes in HIV DNA or the proportion of cells with inducible MS HIV RNA. P2 demonstrated a striking increase in the frequency of gag-specific central and effector memory CD8+ T cells producing IFN-γ, TNF-α, and CD107a following anti-PD1 and anti-CTLA-4. The frequency of CD8+ Tpex cells pre-ICB was also highest in this participant.\n\n\nCONCLUSIONS\nIn three PLWH with cancer on ART, we found that ICB activated latent HIV and enhanced HIV-specific T cell function but with considerable variation.