Functional T Cell Responses Are Associated With Prolonged HIV Control After Treatment Interruption.

BACKGROUND: CD8+ T cell responses are thought to be critical for spontaneous control of human immunodeficiency virus (HIV) but findings supporting their role in post-intervention control have been mixed. We hypothesized that HIV-specific T cell proliferation, interferon-γ (IFN-γ) and granzyme B response prior to analytical treatment interruption (ATI) were associated with time to viral rebound. METHODS: We pooled data from six different HIV cure trials including people living with HIV receiving antiretroviral therapy (ART) alone or combined with latency reversing agents, Toll-Like receptor 9 agonists or broadly neutralizing antibodies. Pre-ATI blood samples were analysed by IFN-γ ELISpot and lymphocyte proliferation assay (LPA). RESULTS: We included 91 participants (90% male, median age 45 years). Compared to participants without virologic control (two consecutive measurements >1000 copies of HIV RNA/mL or ART restart), participants with virologic control at day 28 post-ATI (n=49) had higher Gag-specific IFN-γ (210 vs. 50 SFC/106 PBMCs, p=0.03) and CD8+ T cell proliferation (0.48% vs. 0.16%, p=0.03) responses pre-ATI. The median duration of virologic control was 28 vs. 21 days in people with high vs low Gag-specific IFN-γ response (p<0.01) or CD8+ T cell proliferation (p=0.03). ELISpot and LPA responses were not associated with time to first plasma HIV RNA of >50 copies/mL. CONCLUSIONS: These findings indicate that high pre-ATI Gag-specific IFN-γ and CD8+ T cell proliferation responses were associated with an increase in the duration of virological control after stopping ART, supporting a role for CD8+ T cells in sustaining virological control.