Anti-PD-L1 antibody ASC22 in combination with a histone deacetylase inhibitor chidamide as a “shock and kill” strategy for ART-free virological control: a phase Ⅱ single-arm study

The combination of ASC22, an anti-PD-L1 antibody potentially enhancing HIV-specific immunity and chidamide, a HIV latency reversal agent, may serve as a strategy for antiretroviral therapy-free virological control for HIV. People living with HIV, having achieved virological suppression, were enrolled to receive ASC22 and chidamide treatment in addition to their antiretroviral therapy. Participants were monitored over 24 weeks to measure changes in viral dynamics and the function of HIV-specific CD8^(+) T cells (NCT05129189). 15 participants completed the study. At week 8, CA HIV RNA levels showed a significant increase from baseline, and the values returned to baseline after discontinuing ASC22 and chidamide. The total HIV DNA was only transiently increased at week 4 (P = 0.014). In contrast, integrated HIV DNA did not significantly differ from baseline. Increases in the proportions of effector memory CD4^(+) and CD8^(+) T cells (TEM) were observed from baseline to week 24 (P = 0.034 and P = 0.002, respectively). The combination treatment did not succeed in enhancing the function of HIV Gag/Pol- specific CD8^(+) T cells. Nevertheless, at week 8, a negative correlation was identified between the proportions of HIV Gag-specific TEM cells and alterations in integrated DNA in the T cell function improved group (P = 0.042 and P = 0.034, respectively). Nine adverse events were solicited, all of which were graded 1 and resolved spontaneously. The combined treatment of ASC22 and chidamide was demonstrated to be well-tolerated and effective in activating latent HIV reservoirs. Further investigations are warranted in the context of analytic treatment interruption.

Antiretroviral therapy-naïve people living with HIV tend to have more severe symptoms of COVID-19

To the Editor:Coronavirus disease 2019(COVID-19),instigated by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has manifested as a formidable global pandemic,precipitating significant economic implications and leading to extensive mortalities.Simultaneously,the acquired immune deficiency syndrome(AIDS)epidemic caused by the human immunodeficiency virus(HIV)persists as a salient global health exigency.Cumulatively by the termination of 2022,AIDS-related pathologies accounted for approximately 40.4 million fatalities,with an extant global HIV population of roughly 39 million people living with HIV(PLWH),as a potentially immunocompromised population,have received limited attention in the realm of COVID-19 research.

Special issue on “Molecular Sensors and Molecular Logic Gates”

This issue of Frontiers of Chemical Science and Engineering highlights recent progress toward fluorescent probes that was originally conceived to coincide with 7th Conference on Molecular Sensors and Molecular Logic Gates(MSMLG 2020)to celebrate the career of Seiji Shinkai and hosted by Anthony Czarnik at the University of Nevada in Reno.Sadly,that meeting was cancelled due to the pandemic associated with COVID-19.However,this collection of research and review papers will now serve as an introduction to MSMLG 2022 which will be in Dublin,Ireland on 7–10 June 2022,where Thorfinnur Gunnlaugsson will be the local host.The collection of papers contained in this special issue covers in vitro and in vivo applications and illustrates the potential for practical sensing and imaging of disease-related species.