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.

Potential therapeutic options for coronavirus disease 2019:using knowledge of past outbreaks to guide future treatment

In December 2019,initial cases of the novel coronavirus(2019-nCoV)infection,termed coronavirus disease 2019(COVID-19),were first reported in Wuhan,China.[1]In humans,infections with the human coronavirus 229E,OC43,NL63,and HKU1 usually result in mild,selflimiting upper respiratory tract infections.However,other variants have rapid transmission rates and can cause severe respiratory syndrome and death.These variants include severe acute respiratory syndrome coronavirus(SARSCoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and the current 2019-nCoV.

Fungal Translocation Marker in People Living with HIV Needing Treatment for Onychomycosis: A Protocol for the Prospective Pilot Study

Increased microbial translocation and chronic immune activation are two critical problems for people living with HIV(PLWH)in the antiretroviral therapy(ART)era.Compared with numerous studies on bacterial microbiomic communities,there are only a limited number of studies focusing on fungal microbiomic composition and products in PLWH.This study protocol is used to evaluate the changes in bacterial and fungal microbiome populations induced by terbinafine treatment,which is an antifungal agent widely used amongst PLWH.Twenty-two PLWH on a stable ART regimen for more than six months,who require treatment for onychomycosis,will be recruited.The participants will be followed-up for a 12-week treatment period(oral terbinafine 250mg daily)and another 12-weeks of terbinafine discontinuation.Plasma and fecal samples will be collected before and after terbinafine treatment,and for 12weeks after the discontinuation of terbinafine.Plasma gut injury and microbial translocation biomarker assays,in addition to testing for gut microbiome composition,will be undertaken.With this pilot study,we will perform formal sample size calculations and test study feasibility for a possible full-scale study.

HIV Compartmentalization in Male Genital Tract:Relevance for Viral Eradication

Human immunodeficiency virus(HIV)has been shown to evolve independently in different anatomical compartments.Characterizing HIV genetic evolution in different tissues and cells provides insights into the mechanisms that maintain the viral reservoir.HIV compartmentalization has been well documented in the semen but rarely in male genital tract(MGT)organs.The precise mechanisms that result in the development of HIV compartmentalization in multiple genitourinary sites have been poorly explored due to the difficulty in accessing these tissues.Based on evidence from lymph nodes and gut tissues,mechanisms that may influence compartmentalization include immune pressures,local concentrations of antiviral drugs,clonal expansion of different cell types and inflammation that alters the cellular microenvironment.We reviewed phylogenetic evidences supporting viral compartmentalization between the blood and multiple genitourinary sites in HIV-infected people.Characterizing distinct viral subpopulations enhances our overall understanding of the HIV reservoir inMGTand could ultimately lead to the development of novel therapies to eradicate the virus in tissues.