Abstract
OBJECTIVE: The aim of this study was to quantify HIV-specific immunological and virological changes in people with HIV (PWH) on antiretroviral therapy (ART) with malignancy who received immune checkpoint blockade (ICB). DESIGN: An observational cohort study. METHODS: Blood 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 unspliced HIV RNA, cell-associated 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). RESULTS: Participant (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 three 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. CONCLUSION: In three PWH with cancer on ART, we found that ICB activated latent HIV and enhanced HIV-specific T cell function but with considerable variation.
Original language | English |
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Pages (from-to) | 1631-1636 |
Number of pages | 6 |
Journal | AIDS |
Volume | 35 |
Issue number | 10 |
DOIs | |
Publication status | Published - 1 Aug 2021 |
Prizes
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Australasian Society of Infectious Diseases Council Scholarship
Lau, Jillian (Recipient), 26 Mar 2021
Prize: Prize (including medals and awards)
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Australasian Society of Infectious Diseases Viral Hepatitis Special Interest Group (VHSIG) Award
Lau, Jillian (Recipient), 26 Mar 2021
Prize: Prize (including medals and awards)
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Conference on Retroviruses and Opportunistic Infections New Investigator Scholarship
Lau, Jillian (Recipient), 15 Nov 2019
Prize: Prize (including medals and awards)