2027. Immune Correlates of Protection Against Herpes Zoster (HZ) in People Living with HIV (PLWH)

BACKGROUND: HZ has high morbidity in immune-compromised hosts, including PLWH. Two vaccines against HZ are available, but their efficacy in PLWH is unknown. A surrogate marker of protection against HZ would facilitate efficacy studies of HZ vaccines in PLWH, as compared with HZ clinical outcome studies. To this goal, our study investigated the association of cytotoxic T lymphocytes (CTL) and regulatory T cells (Treg) with incident HZ in PLWH. METHODS: The study used peripheral blood mononuclear cells (PBMC) cryopreserved at mean (SD) of 2.7 (2.5) months before HZ from 31 PLWH cases on ART with plasma vRNA < 200 c/mL, and CD4 counts ≥200 cells/µL. 31 non-HZ controls were matched to cases by CD4 count, age, sex, race, parent study, and ART duration. T cell subsets were measured by flow cytometry after ex vivo VZV- and mock-restimulation and in freshly thawed unstimulated PBMC using the following markers: CD3, CD8, CD25, CD28, CD39, CD57, CD127, CTLA4, FOXP3, IFNg, IL10, KLRG1, LAG3, PD1, perforin, TGFb, TIM3 and TNFa. Data were analyzed by paired t-tests. RESULTS: At PBMC collection, PLWH had mean (SD) age 41 (10) years; 16 females; 28 White and 22 Black non-Hispanics; mean (SD) CD4 counts 501 (222) cells/µL; 56 (90%) vRNA < 50 c/mL; median ART duration 50 weeks. In unstimulated PBMC, HZ cases had higher %FOXP3+CD25+(CD4+) Treg compared with controls (P = 0.08). Cases generally had lower responses to ex vivo VZV-restimulation (after subtraction of mock) compared with controls, including %perforin+(CD8+) CTL (P = 0.07) and %IL10+(CD4+) (P = 0.04) and %TGFb+(CD4+) Treg (P = 0.07). %FOXP3+CD25+(CD4+) Treg in unstimulated PBMC did not correlate with VZV-specific %perforin+(CD8+) or %IFNg+(CD4+) effector T cells, but the VZV-specific effector T cell percentages correlated with each other (r = 0.24, P = 0.05). CONCLUSION: Although limited by small numbers, this study showed that before development of HZ, PLWH had marginally increased number of Treg in blood and decreased VZV-specific responses. VZV-specific Treg and CTL were equally lower in cases compared with controls, suggesting that a general low VZV-specific T cell responsiveness precedes HZ in PLWH. The lack of association between circulating Treg and VZV-specific T cell responses suggests independent mechanisms of action. DISCLOSURES: All authors: No reported disclosures.