The administration of COVID-19 vaccines is the primary strategy used to prevent further infections by COVID-19, especially in people living with HIV (PLWH), who are at increased risk for severe symptoms and mortality. However, the vaccine hesitancy, safety, and immunogenicity of COVID-19 vaccines among PLWH have not been fully characterized. We estimated vaccine hesitancy and status of COVID-19 vaccination in Chinese PLWH, explored the safety and impact on antiviral therapy (ART) efficacy and compared the immunogenicity of an inactivated vaccine between PLWH and healthy controls (HC). In total, 27.5% (104/378) of PLWH hesitated to take the vaccine. The barriers included concerns about safety and efficacy, and physician counselling might help patients overcome this vaccine hesitancy. A COVID-19 vaccination did not cause severe side effects and had no negative impact on CD4+ T cell counts and HIV RNA viral load. Comparable spike receptor binding domain IgG titer were elicited in PLWH and HC after a second dose of the CoronaVac vaccine, but antibody responses were lower in poor immunological responders (CD4+ T cell counts < 350 cells/µL) compared with immunological responders (CD4+ T cell counts ≥ 350 cells/µL). These data showed that PLWH have comparable safety and immune response following inactivated COVID-19 vaccination compared with HC, but the poor immunological response in PLWH is associated with impaired humoral response.

Background: Our study aimed to develop a clinical prediction model to evaluate the possibility of CD4 þ /CD8 þ ratio restoration in HIV-positive individuals.Methods: About 1980, HIV/AIDS patients initiated with antiretroviral treatment from 1 January 2013, to 30 December 2016, at Beijing Ditan Hospital and achieved persistent virological suppression during the 4 years follow-up were included in this study. Multivariate Cox proportional regression analysis was used to identify the independent risk factors and establish a predictive model. The model's performance was assessed using the area under the receiver operating characteristic and calibration plots.Results: Overall, after 4 years of treatment, a total of 455 individuals (22.98%) restored their CD4 þ /CD8 þ ratio (!1). The area under the receiver operating characteristic was 0.782 and 0.743 in the deriving and validation cohort, respectively. The ultimate model included five indexes: age at AIDS diagnosis, albumin, and syphilis status, and baseline CD4 þ and CD8 þ values. A nomogram further visualized the model, and the calibration plots indicated high agreement of predicted and observed outcomes. Conclusion:Our prediction model might be practical and easily applied to recognize HIV/AIDS individuals most likely to benefit from modern antiretroviral therapy.

Although extensive use of antiretroviral therapy (ART) has made great progress in controlling HIV replication and improving CD4+ T cell recovery, the immune reconstitution remained insufficient in some patients, who were defined as poor immunological responders (PIRs). These PIRs were at a high risk of AIDS-related and non-AIDS complications, resulting in higher morbidity and mortality rate. Thus, it is a major challenge and urgently needed to distinguish PIRs early and improve their immune function in time. Immune activation is a key factor that leads to impaired immune reconstitution in people living with HIV (PLWH) who are receiving effective ART. Double negative T cells (DNT) were reported to associate with the control of immune activation during HIV infection. However, the precise mechanisms by which DNT cells exerted their suppressive capacity during HIV infection remained puzzled. CD73, both a soluble and a membrane-bound form, display immunosuppressive effects through producing adenosine (ADO). Thus, whether DNT cells expressed CD73 and mediated immune suppression through CD73-ADO pathway needs to be investigated. Here, we found a significant downregulation of CD73 expression on DNT cells in treatment-naïve PLWH (TNs) compared to healthy controls, accompanied with increased concentration of sCD73 in plasma. Both the frequency of CD73+ DNT cells and the level of plasma sCD73 recovered after ART treatment. However, PIRs showed decreased percentage of CD73+ DNT cells compared to immunological responders (IRs). The frequency of CD73+ DNT cells was positively correlated with CD4+ T cell count and CD4/CD8 ratio, and negatively correlated with immune activation in PLWH. The level of sCD73 also showed a negative correlation to CD4+ T cell count and CD4/CD8 ratio. More importantly, in the present cohort, a higher level of sCD73 at the time of initiating ART could predict poor immune reconstitution in PLWH after long-term ART. Our findings highlighted the importance of CD73+ DNT cells and sCD73 in the disease progression and immune reconstitution of PLWH, and provided evidences for sCD73 as a potential biomarker of predicting immune recovery.

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Background Efavirenz (EFV)-induced neuropsychiatric toxicity bothers people living with HIV (PLHIV). Neuropsychiatric adverse effects of EFV may differ by length of time on EFV-based antiretroviral treatment (ART). Methods A cross-sectional, single-center study was conducted at Beijing Ditan Hospital in China from June–August 2020 among ART-experienced PLHIV who were on long-term EFV-based ART. 424 eligible virological suppressed participants were enrolled and divided into four groups according to time on EFV-based ART: group A (0.5 ≤ ART < 2 year), B (2 ≤ ART < 4 year), C (4 ≤ ART < 6 year), and D (ART ≥ 6 year). The questionnaires about 12-item Short Form Health Survey (SF-12), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) were administered to assess neuropsychiatric adverse events of EFV among different groups. Results Overall mental component summary scores (MCS) of SF-12 in PLHIV was 50.2, which was lower than general population. Overall prevalence of anxiety, depression and sleep disturbances was 15.6%, 15.3% and 58%, respectively. Prevalence of anxiety, depression and sleep disturbances did not vary significantly between the time-on-ART groups. Anxiety, depression, sleep disturbances had no correlation with time on EFV-based ART or CD4+ T cells counts. Conclusions In ART-experienced PLHIV in China, neuropsychiatric adverse events exist persistently and prevalence do not significantly change with prolonged time on EFV-based ART. The prevalence of sleep disturbances was high, suggesting that clinicians should pay more attention to long-standing psychiatric health to perform early and effective interventions.

Aging leads to functional dysregulation of the immune system, especially T cell defects. Previous studies have shown that the accumulation of co-inhibitory molecules plays an essential role in both T cell exhaustion and aging. In the present study, we showed that CD244 and CD160 were both up-regulated on CD8+ T cells of elderly individuals. CD244+CD160- CD8+ T cells displayed the increased activity of β-GAL, higher production of cytokines, and severe metabolic disorders, which were characteristics of immune aging. Notably, the functional dysregulation associated with aging was reversed by blocking CD244 instead of CD160. Meanwhile, CD244+CD160+ CD8+ T cells exhibited features of exhaustion, including lower levels of cytokine, impaired proliferation, and intrinsic transcriptional regulation, compared to CD244+CD160- population. Collectively, our findings demonstrated that CD244 rather than CD160 acts as a prominent regulator involved in T cell aging, providing a solid therapeutic target to improve disorders and comorbidities correlated to immune system aging.

Persistent immune activation, which occurs during the whole course of HIV infection, plays a pivotal role in CD4+ T cells depletion and AIDS progression. Furthermore, immune activation is a key factor that leads to impaired immune reconstitution after long-term effective antiretroviral therapy (ART), and is even responsible for the increased risk of developing non-AIDS co-morbidities. Therefore, it’s imperative to identify an effective intervention targeting HIV-associated immune activation to improve disease management. Double negative T cells (DNT) were reported to provide immunosuppression during HIV infection, but the related mechanisms remained puzzled. Foxp3 endows Tregs with potent suppressive function to maintain immune homeostasis. However, whether DNT cells expressed Foxp3 and the accurate function of these cells urgently needed to be investigated. Here, we found that Foxp3+ DNT cells accumulated in untreated people living with HIV (PLWH) with CD4+ T cell count less than 200 cells/µl. Moreover, the frequency of Foxp3+ DNT cells was negatively correlated with CD4+ T cell count and CD4/CD8 ratio, and positively correlated with immune activation and systemic inflammation in PLWH. Of note, Foxp3+ DNT cells might exert suppressive regulation by increased expression of CD39, CD25, or vigorous proliferation (high levels of GITR and ki67) in ART-naive PLWH. Our study underlined the importance of Foxp3+ DNT cells in the HIV disease progression, and suggest that Foxp3+ DNT may be a potential target for clinical intervention for the control of immune activation during HIV infection.

2010 1,2 . However, cardiovascular complications, such as pulmonary arterial hypertension (PAH), cause great burden in PLWH 3,4 . Regardless of ART introduction, the prevalence of HIV-related PAH is 0.5%, whatever before and after ART era, which is 25-fold higher than that in the general population 5 . The prevalence of HIV-related PAH, as reported by studies using echocardiography, is as high as 2.6-27.8% 6,7 . Among PLWH, the