Clinical outcomes of people living with human immunodeficiency virus (HIV) with diffuse large B-cell lymphoma (DLBCL) in Shanghai, China / 中华医学杂志(英文版)

BACKGROUND@#Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus (HIV). However, little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV (PLHIV). Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab(R-CHOP) as front line therapy for PLHIV with diffuse large B-cell lymphoma (DLBCL) receiving modern combined antiretroviral therapy (cART).@*METHODS@#A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019. The demographic and clinical data were collected, and overall survival (OS) and progression-free survival (PFS) analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis. Additionally, a Cox multiple regression model was constructed to identify related factors for OS.@*RESULTS@#A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months (interquartile range [IQR]: 8-29 months). The proportion of high international prognostic index (IPI) patients was much larger in the DA-EPOCH-R group (n = 29) than that in the R-CHOP group (n = 25). The CD4 cell counts and HIV RNA levels were not significantly different between the two groups. The 2-year OS for all patients was 73%. However, OS was not significantly different between the two groups, with a 2-year OS rate of 78% for the DA-EPOCH-R group and 66% for the R-CHOP group. Only an IPI greater than 3 was associated with a decrease in OS, with a hazard ratio of 5.0. The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups.@*CONCLUSIONS@#Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy. No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART era.

Clinical features and treatment outcomes of human immunodeficiency virus-associated cryptococcal meningitis: a 2-year retrospective analysis / 中华医学杂志(英文版)

BACKGROUND@#Cryptococcal meningitis (CM) is one of the most common opportunistic infections caused by Cryptococcus neoformans in human immunodeficiency virus (HIV)-infected patients, and is complicated with significant morbidity and mortality. This study retrospectively analyzed the clinical features, characteristics, treatment, and outcomes of first-diagnosed HIV-associated CM after 2-years of follow-up.@*METHODS@#Data from all patients (n = 101) of HIV-associated CM hospitalized in Shanghai Public Health Clinical Center from September 2013 to December 2016 were collected and analyzed using logistic regression to identify clinical and microbiological factors associated with mortality.@*RESULTS@#Of the 101 patients, 86/99 (86.9%) of patients had CD4 count <50 cells/mm, 57/101 (56.4%) were diagnosed at ≥14 days from the onset to diagnosis, 42/99 (42.4%) had normal cerebrospinal fluid (CSF) cell counts and biochemical examination, 30/101 (29.7%) had concomitant Pneumocystis (carinii) jiroveci pneumonia (PCP) on admission and 37/92 (40.2%) were complicated with cryptococcal pneumonia, 50/74 (67.6%) had abnormalities shown on intracranial imaging, amongst whom 24/50 (48.0%) had more than one lesion. The median time to negative CSF Indian ink staining was 8.50 months (interquartile range, 3.25-12.00 months). Patients who initiated antiretroviral therapy (ART) before admission had a shorter time to negative CSF Indian ink compared with ART-naïve patients (7 vs. 12 months, χ = 15.53, P < 0.001). All-cause mortality at 2 weeks, 8 weeks, and 2 years was 10.1% (10/99), 18.9% (18/95), and 20.7% (19/92), respectively. Coinfection with PCP on admission (adjusted odds ratio [AOR], 3.933; 95% confidence interval [CI], 1.166-13.269, P = 0.027) and altered mental status (AOR, 9.574; 95% CI, 2.548-35.974, P = 0.001) were associated with higher mortality at 8 weeks.@*CONCLUSION@#This study described the clinical features and outcomes of first diagnosed HIV-associated CM with 2-year follow-up data. Altered mental status and coinfection with PCP predicted mortality in HIV-associated CM.

Proteomic study on effect of tangcao pill on microsome CYP450 / 中国中药杂志

Tangcao pill is commonly applied in adjuvant and even alternative therapy for patients with AIDS. However, the herb contains complex ingredients, but with unknown effect against anti-HIV drug and unknown function. Because CYP450 emzyme is the main metabolic enzymes of the drug, it is of important significance to study the regulation of CYP450 enzymes before and after the combined administration of Tangcao pill and EFV. Proteomics, due to its high throughout and high sensitivity, has been widely applied in CYP450 enzyme study. In this paper, liver microsomes were separated through differential centrifugation. Their proteins were separated through SDS-PAGE. The three protein bands that CYP450 enzymes were located were cut and identified by liquid chromatography tandem mass spectrometry. Totally 16 CYP450 isoenzymes were identified. Furthermore, in order to make a quantitative analysis on the effect of tang herb on CYP450 emzyme, the multiple reaction monitoring (MRM) technology based on MS was adopted. The CYP2C11 was selected based on the results of the mass spectrum identification of proteins. The characteristic polypeptides were obtained through searching Expasy blast database. The m/z of the fragment ions was less than 800. In the paper, the m/z of ion pairs of CYP2C11 were 711.5/232.1, 711.5/319.2, 711.5/466.2 and 711.5/595.3, and the m/z of ESAT-6 (internal standard, IS) were 735.5/215.3, 735.5/389.3, 735.5/460.3 and 735.5/524.3. The relative peak (analyte/IS) area was adopted for the relative quantitative analysis. Compared with the EFV single administration group, the EFV and Tangcao pill combined administration group showed a 1.6-fold increase in CYP2C11. The results of the paper indicated that Tangcao pill may affect drug metabolism by regulating metabolic enzymes such as CYP2C11, but the specific mechanism still unknown.

Epidemiological and clinical features of occult hepatitis B in HIV infection without antiretroviral treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate and analyze the differential prevalence, as well as the risk factors and clinical features, of occult hepatitis B virus (HBV) infection in the human immunodeficiency virus (HIV)-infected population without antiretroviral therapy (ART) as compared to the general (non-HIV-infected) population.</p><p><b>METHODS</b>Two-hundred-and-forty-eight individuals with confirmed HIV infection but ART naive (males: 220, females: 28; 15-82 years old) were enrolled in the study, along with 121 healthy individuals (confirmed HIV antibody-negative; males: 53, females: 68; 20-88 years old). HBV markers (hepatitis B surface antigen (HBsAg); hepatitis B e antigen (HBeAg); anti-HBs, anti-HBe and anti-hepatitis B core (HBc) antibodies) were detected by microparticle enzyme-linked immunosorbent assay (AxSYM immunology analyzer manufactured by Abbott Laboratories); all cases and controls were confirmed negative for hepatitis B surface antigen (HBsAg). Then, the HBV DNA level in serum was detected using nucleic acid amplification assay (COBAS AmpliPrep/COBAS TaqMan HBV test, version 2.0 manufactured by Roche). CD4+ T lymphocytes were measured by flow cytometry, and alanine aminotransferase (ALT, marker of liver function) was measured by enzymatic assay.</p><p><b>RESULTS</b>Twenty-four of the HIV cases (9.7%) and four of the healthy controls (3.3%) tested positive for HBV DNA; the amount of individuals with HBV DNA-positivity was significantly higher in the HIV-infected group (P = 0.035). Among the 24 cases of HBV DNA(+) HIV-infected individuals, the lowest HBV DNA load was < 20 IU/ml and the highest was 3.22 x 10s IU/ml; nine of the individuals (37.5%) had HBV DNA load > 100 IU/ml, four (16.7%) had 20-99 IU/ ml, and 11 (45.8%) had < 20 IU/ml. Among the total HIV-infected cases with HBV DNA-positivity, 7.3% (8/110) were anti-HBc(+)/anti-HBs(+), 20.8% (11/53) were anti-HBc(+)/anti-HBs(-), 14.3% (3/21) were anti-HBc(-)/anti-HBs(+), and 3.1% (2/64) were anti-HBc(-)/anti-HBs(-). The amount of individuals with HBV DNA-positivity in the anti-HBc(+)/anti-HBs(-) group was significantly different from those in the anti-HBc(+)/anti-HBs(+) group (P = 0.018) and the anti-HBc(-)/anti-HBs(-) group (P = 0.003). However, multiple comparison of HBV DNA loads detected between the four groups of HBV marker status revealed no significant difference (P = 0.805). Furthermore, statistical analysis provided no evidence to support that occult hepatitis B infection in HIV-infected individuals had any impact on CD4+ T lymphocytes count (Z = 1.902, P = 0.059) or ALT levels (Z =1.401, P = 0.161).</p><p><b>CONCLUSION</b>HIV-infected individuals who are ART naive and HBsAg(-) have a higher incidence of HBV DNA-positivity than individuals in the general (non-HIV-infected) population. In addition, the highest rate of occult hepatitis B among the HIV-infected cases occurred among individuals who were anti-HBc(+)/anti-HBs(-).</p>