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Background Talaromyces marneffei(TM) bloodstream infection is common in AIDS patients with extreme immunodeficiency in Southeast Asia and South China, however, clinical case study on TM bloodstream infection is scarce. We retrospectively analyze the clinical characteristics of TM bloodstream infection in hospitalized AIDS patients and determine the outcomes of hospitalization after diagnosis in our hospital over the past 5 years.Methods From January 2015 to July 2020, cases of TM detected by blood culture in patients admitted to our center were sorted and analyzed. The admission complaints, blood cells, biochemistry, CD4/CD8 count and 1,3-β-D-glucan, procalcitonin, CRP level on the day of blood culture test, and outcomes during hospitalization were analyzed. Logistic regression analysis was performed for the risk factors for poor prognosis. Spearman correlation analysis was used to analyze the correlation between peripheral blood cells, albumin and the time required for TM to become positive in blood culture. The difference was statistically significant when the P value was 200/µl (p=0.04), and those with 1,3-β-D-glucan 100 pg/mL (p=0.01).Conclusions TM bloodstream infection is becoming more common in advanced AIDS patients in endemic areas. For those patients with extremely low CD4 and CD8 cell counts below 200/µl, the 1,3-β-D-glucan

Background The combination of KIR-HLA affects the prognosis of HIV infection, and polymorphisms of KIR and its ligand HLA differs between regions and races. Few research has focused on the effects of the KIR-HLA combination on the prognosis of HIV-infected individuals in China. Methods Peripheral blood samples were collected from newly diagnosed and treatment naïve HIV-infected patients and processed according to the study design. Their clinical data and other demographic information were recorded. The genomic DNA of the host was extracted from whole blood samples, and KIR genotyping was performed using sequence specific primer amplification (PCR-SSP). The HLA genotyping was performed using sequence analysis (PCR-SBT), and the HLA-KIR genotyping and combination information were obtained. Fisher’s exact test was used for the comparison of categorical variables between groups, and the Mann-Whitney test was used for continuous variables. Results The baseline HIV level in patients with an HLA-C1+/KIR2DL3+ background was significantly higher than that in patients with an HLA-C1+/KIR2DL3- (4.34 log10 copies/ml vs. 3.72 log10 copies/ml, P=0.02). The baseline CD4/CD8 ratio of HLA-C1+/KIR2DL3+ patients was significantly lower than that of HLA-C1+/KIR2DL3- patients (0.33 vs. 0.56, P=0.02). The plasma soluble CD14 level at baseline was significantly lower in HLA-C1+/KIR2DL3- infected persons than HLA-C1+/KIR2DL3+ patients (P=0.03). Conclusions HIV-infected persons with the combination of HLA-C1+/KIR2DL3+ had a much higher HIV set point, higher baseline sCD14 levels and lower baseline CD4/CD8 than patients without this combination. The receptor-ligand combination of HLA-C1+/KIR2DL3+ has a deleterious effect in Chinese HIV patients.

Vancomycin plays an important role in the treatment of concurrent infections in severe coronavirus disease 2019 (COVID-19) patients. However, few is known about its pharmacokinetics (PK) in these patients. Here we performed therapeutic drug monitoring (TDM) of intravenous vancomycin with or without nasal administration in these patients. Drug dosage was adjusted depending on vancomycin concentration. A population PK model was developed using NONMEM software. Therapeutic effects, and vancomycin-related adverse events were monitored. A total of 63 samples from 8 patients were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. The mean trough and peak concentration were 13.79±6.61 (4.63-34.2) mg/L (n=36) and 30.97±9.71 (17-49.9) mg/L (n=27), respectively. 25.4% of serum vancomycin concentration was beyond optimal range. Dose adjustments were made for 3 patients. The PK of vancomycin was consistent with two-compartment model, with the clearance and distribution volume in the central compartment of 4.3 L/h and 2.0 L, respectively. The AUC0-24/MIC of vancomycin was 848±566 h. Target infection was clinically cured in all patients, and no vancomycin-associated nephrotoxicity was detected during the TDM process. In conclusion, the PK studies of vancomycin in COVID-19 patients are needed to optimize drug dosage. Based on our PK model, the clearance of vancomycin was 4.3 L/h.

Background To investigate the clinical manifestations, imaging findings, characteristics of cerebrospinal fluid, treatment and prognosis in patients with AIDS-related progressive white matter lesions diagnosed by second-generation sequencing with cerebrospinal fluid.Methods Patients with clinically suspected PML were diagnosed by second-generation sequencing with cerebrospinal fluid, and the clinical data of these patients were retrospectively reviewed.Results Ten patients with AIDS-related PML were diagnosed, including eight males (80%). The average age was 38.7±8.2 years, and the median CD4+ T cell count was 46×106/L. The median HIV RNA was 5.99 × 104 copies/ml. Main clinical manifestations included: dyskinesia in 4 patients (40%) and dizziness in 3(30%), cognitive decline in 2(20%), and speech disorder in 1(10%). Three patients (30%) developed convulsions throughout the course of the disease. Image findings involved lesions cerebellum in 3 cases (30%), and lesions above the cerebellum in 7 cases (70%). Mild increase of total protein was observed in the cerebrospinal fluid of 4 cases (40%), while white blood cell count, sugar and chloride were normal in all of the cases. The copies of JCV sequence in the cerebrospinal fluid ranged from 3-12531 reads (median=67 reads). All the patients received antiviral therapy including integrase inhibitors. Among the 10 patients, 2 died in hospital and 8 survived, 2 of them have survived for more than 1 year. Symptoms were improved in 5 patients and unchanged in 3 patients.Conclusions PML is common in patients with HIV/AIDS. It is reliable to diagnose the disease through clinical manifestations, routine detection of cerebrospinal fluid, imaging and cerebrospinal fluid NGS sequencing. Strong and effective antiretroviral treatment may improve the prognosis of patients.