Editor’s Note: The IDWeek in the United States is one of the largest infectious disease academic conferences globally, often referred to as the “Oscars” of the infectious disease field. Numerous cutting-edge research findings would be shared and discussed at this highly anticipated academic event. During the recent 2023 IDWeek, Dr. Yaokai Chen’s team from Chongqing Public Health Medical Center had four HIV-related research findings selected for the conference. One of these was presented as a Rapid-Fire Poster, while the other three were included in poster presentations.
Chongqing Public Health Medical Center /Southwest University Public Health Hospital
Cryptococcal Antigen Screening and Pre-emptive Fluconazole Therapy in HIV-infected Patients: A Multicenter, Retrospective Study in China (Abstract No: 1497)
Cryptococcal antigenemia refers to the presence of Cryptococcus antigen (CrAg) in the blood without evidence of active cryptococcal infection in target organs. Research has shown that cryptococcal antigenemia is a risk factor for cryptococcal meningitis (CM) and mortality in HIV-infected individuals. Prophylactic fluconazole treatment has been effective in reducing the incidence of CM and mortality in this patient population. However, there is currently a lack of large-scale studies in China on the prevalence of cryptococcal antigenemia in HIV-infected patients and the efficacy of fluconazole prophylactic treatment.
The team conducted a multicenter retrospective study in eight hospitals across China. They collected data from HIV-infected patients who underwent serum CrAg testing between January 2019 and December 2022. Patients with clear evidence of active cryptococcal infection in target organs or incomplete data were excluded.
The results showed that the overall prevalence of cryptoccocal antigenemia among HIV-infected patients was approximately 5.3%. Those who did not receive prophylactic fluconazole treatment (n = 42) had a significantly increased risk of developing CM and/or death compared to those who received prophylactic fluconazole treatment (n = 81) (aHR: 3.035, 95% CI: 1.067—8.635; P = 0.037).
Among the 81 patients with cryptococcal antigenemia who received fluconazole treatment, 32 received the WHO-recommended fluconazole dosage (induction phase: 800mg/day for 2 weeks, followed by consolidation and maintenance therapy, with a total treatment duration of at least 1 year), and 49 received oral fluconazole at a daily dose of 400mg, with a total treatment duration of at least 1 year. The former group had a 1-year incidence rate of cryptococcal meningitis (CM) and/or death of 9.4% (3/32), while the latter group had a 1-year incidence rate of 8.7% (4/49), with no significant difference between the two groups (P=0.836).
► Conclusion: Among HIV-infected individuals in China, the overall prevalence of cryptococcal antigenemia exceeds 3%, meeting the high prevalence criteria defined by WHO. Prophylactic fluconazole treatment is an effective strategy for reducing the incidence of cryptococcal meningitis (CM) and the risk of death.
Landscape of peripheral blood mononuclear cell single-cell transcriptomes in HIV-infected patients with cryptococcal meningitis (Abstract No: 1485)
To further understand the immunopathogenic mechanisms of HIV-associated cryptococcal meningitis (HIV-CM), the research team employed single-cell nuclear sequencing to compare transcriptome changes in peripheral blood mononuclear cells (PBMCs) among ART-naive HIV-CM patients (n=8), ART-naive HIV-infected individuals (n=8), and healthy control subjects (HC). They also analyzed changes in the single-cell transcriptome of HIV-CM patients before and after antifungal treatment to assess its impact.
The study obtained a total of 318,718 PBMCs and identified 20 cell subtypes based on gene expression. In the PBMC samples, compared to HC, HIV-CM patients exhibited a significant decrease in the percentage of CD4+ T cells and NK cells and an increase in the percentage of CD14 monocytes. When compared to HIV-infected individuals, only the percentage of CD4+ T cells in HIV-CM patients showed significant changes. Moreover, after four weeks of antifungal treatment, the percentages of these three cell types also exhibited significant changes. Following treatment, it was observed that the CD4+ T cell proportion in HIV-CM patients was lower than in HC but similar to that of HIV-infected individuals. The relative proportions of NK cells and CD14 monocytes were also reversed, returning to normal levels. The genes differentially expressed in a HIV-CM-specific manner among these three cell types were associated with functions related to cytoplasmic translation, signal recognition particle (SRP)-dependent co-translational protein targeting, viral progression, and other processes. After antifungal treatment, the reversal rate of these differentially expressed genes ranged from 11.7% to 22.9%. The reversed genes were primarily involved in neutrophils, degranulation, and immune system progression.
Optimal timing of antiretroviral therapy initiation in AIDS-associated Toxoplasma encephalitis: a prospective observational multicenter study in China (Abstract No: 1583)
Toxoplasma encephalitis is one of the most common intracranial lesions in patients with acquired immunodeficiency syndrome (AIDS). There is still debate about the optimal timing for initiating antiretroviral therapy (ART) in these patients.
This prospective observational study was conducted at 11 centers in China and included 87 patients. Of these, 38 initiated ART early (within two weeks of starting toxoplasmosis treatment), while 49 initiated ART late (two weeks after starting toxoplasmosis treatment). The study found no significant differences between the two groups in terms of the number of deaths at 48 weeks (1 vs. 5, P=0.225) or the incidence of immune reconstitution inflammatory syndrome (IRIS) (2.6% vs. 0, P=0.437).
In this study, early initiation of ART in HIV-related toxoplasma encephalitis patients showed no statistically significant differences in terms of mortality, IRIS, virologic suppression, and immunological outcomes compared to delayed initiation of ART.
The study also found that the timing of ART initiation had no significant impact on the control of HIV viral load. At week 24 (8 vs. 3 cases, P=0.142) and week 48 (7 vs. 7 cases, P=1.000), there was no significant difference in the number of patients in both groups with HIV viral load less than 50 copies/mL. Additionally, at week 24 (155 vs. 91 cells/mm³, P=0.837) and week 48 (181 vs. 146 cells/mm³, P=0.219), there were no significant differences in CD4 cell counts.
Conclusion: In this study, there were no statistically significant differences in terms of mortality, IRIS, HIV virological suppression rate, and immunological outcomes between HIV-associated toxoplasma encephalitis patients who initiated ART early and those who delayed ART initiation.
Frailty is Associated with Intestinal Barrier Dysfunction in Aging People Living with HIV (Abstract No: 1613)
Intestinal damage and microbial translocation are hallmarks of HIV infection and can promote and sustain chronic systemic inflammation in people living with HIV (PLWH). Furthermore, chronic inflammation can lead to weakness. This cross-sectional study aimed to elucidate the relationship between weakness and intestinal barrier dysfunction and translocation.
This study included 151 PLWH aged 50 and over, and the patients were divided into three groups: non-weak (73 cases), pre-weakness (61 cases), and weakness (17 cases). The results of the study showed significant differences (P < 0.05) among the three groups in terms of difficulties in understanding instructions and communication, community activities, social participation, and self-care. Additionally, the weakness group had a higher incidence of anxiety, depression, and stress compared to the other two groups (P < 0.05).
Further analysis of serum concentrations of intestinal injury biomarkers revealed a significant positive correlation with weakness, particularly observed at the highest levels in the weakness group, for Regenerating Islet-Derived Protein-3α (Reg-3α) and Intestinal Fatty Acid-Binding Protein (I-FABP). Conversely, no significant associations were observed between hematological biomarkers of microbial translocation and weakness. Additionally, concentrations of IL-6, IP-10, and TNF-α in plasma were positively correlated with weakness in elderly people living with HIV (with the highest concentrations observed in the weakness group).
Conclusion: The results of the study above suggest that inflammation caused by intestinal damage may contribute to weakness in elderly people living with HIV.
TAG: IDWeek 2023, Voice of China, HIV
