Amay Shah, Carlo Sacdalan, Robert Gorelick, Derek Macmath, Christophe Vanpouille, Peiying Ye, Ginevra Bugani, Eugène Kroon, Suwanna Puttamaswin, Suteeraporn Pinyakorn, Alexandra Schuetz, Lydie Trautmann, Nittaya Phanuphak, Sandhya Vasan, Andrea Lisco
The anal canal represents the primary site of HIV-1 acquisition in men-who-have-sex-with-men (MSM), while MSM-living-with-HIV (MLWH) have the highest anal cancer incidence. Since HPV16-infection and low-nadir CD4-T-cell counts predict anal cancer risk, we developed an assay to identify and characterize HPV16-specific T-cell responses in MLWH. 40% of acutely and 81% of chronically infected MLWH had HPV16-specific CD4-T-cells, which harbored higher levels of HIV-1 DNA/RNA than non-HPV16-specific CD4-T-cells. T-cell-receptor (TCR) sequencing revealed a less diverse and more restricted TCR-repertoire in HPV16-specific CD4-T-cells. HPV16-specific CD4-T-cells represent an early-established preferential HIV-1 reservoir and a potential novel immunologic correlate of anal cancer-risk in MLWH.