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

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.

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).

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.

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.