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.

Cost-effectiveness evaluation of rapid initiation of antiretroviral therapy based on decision-tree Markov model

To the Editor:Human immunodeficiency virus(HIV)type 1 infection remains a serious and intractable public health problem worldwide.In 2020,there were 37.7 million surviving individuals with HIV infection worldwide and 680,000 HIV-related deaths reported by the Joint United Nations Programme on HIV/acquired immune deficiency syndrome(AIDS)(UNAIDS).

HIV-1 DNA levels in peripheral blood mononuclear cells of patients with HIV-related non-Hodgkin’s lymphoma

To the Editor:Human immunodeficiency virus(HIV)patients have an increased risk of non-Hodgkin’s lymphoma(NHL),even in the era of antiretroviral therapy(ART).[1]The specific mechanisms of HIVrelated NHL(HIV-NHL)remain unclear.It is currently thought that HIV causes lymphoma primarily through chronic immune activation and an increased risk of infection with oncoviruses.In addition,HIV may have some other mechanisms that directly contribute to the occurrence of lymphoma.[2]Even with sustained ART,HIV-DNA remains in infected cells,creating a persistent reservoir of HIV infection.It is not known whether HIV reservoirs are involved in the development of HIV-NHL.In the present study,we detected HIV-1 DNA levels in peripheral blood mononuclear cells(PBMCs)and plasma inflammatory cytokines levels in HIV-NHL,and then evaluated their effects on HIV-NHL development and prognosis.

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.

Long-term case-fatality rate of nontuberculous mycobacterial disease in people living with HIV

Background:Few data are available regarding the long-term case-fatality rate(CFR)among people living with HIV(PLWH)with nontuberculous mycobacteria(NTM)disease.The aim of this study is to analyze the long-term CFR in patients with NTM disease and to identify risk factors for their death.Methods:A retrospective cohort study of 379 cases of microbiologically confirmed NTM disease in PLWH was conducted from January 1,2012,to December 31,2020,in Shanghai,China.We used Kaplan-Meier survival analysis and the log-rank test to compare the long-term CFR in patients with disseminated NTM(DNTM)and localized NTM disease.Univariate Cox proportional hazards regression analysis and a stepwise Cox proportional hazards regression model were used to estimate the predictors of long-term CFR.Results:The cohort was followed up for a median of 26 months.The total CFR was 15.7%by one year and increased to 22.6%at 5 years after the diagnosis of NTM disease.The 5-year CFR of PLWH with DNTM was significantly higher than that of PLWH with localized NTM(26.7%vs 19.6%for DNTM and localized NTM disease,respectively).Older age[hazard ratio(HR)=1.04,95%confidence interval(CI):1.02-1.06,P<0.001],comorbidity(HR=2.05,95%CI:1.21-3.49,P<0.01),DNTM(HR=2.08,95%CI:1.17-3.68,P<0.05),and HIV viral load(HR=1.32,95%CI:1.12-1.55,P<0.001)were all independent risk factors for long-term CFR.In the subgroup analysis,time to culture positivity was negatively correlated with CFR in patients with DNTM(HR=0.90,95%CI:0.82-0.98,P<0.05).Conclusions:NTM was associated with a high long-term CFR in PLWH.Further approaches to prevent NTM disease in PLWH are urgently needed.