Clinical features and treatment outcomes of human immunodeficiency virus-associated cryptococcal meningitis: a 2-year retrospective analysis.

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.

Clinical outcomes of people living with human immunodeficiency virus (HIV) with diffuse large B-cell lymphoma (DLBCL) in Shanghai, China.

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.

Risk factors affecting the mortality of HIV-infected patients with pulmonary tuberculosis in the cART era: a retrospective cohort study in China.

BACKGROUND: Tuberculosis infection still places a great burden on HIV-infected individuals in China and other developing countries. Knowledge of the survival of HIV-infected patients with pulmonary tuberculosis (PTB) would provide important insights for the clinical management of this population, which remains to be well described in current China. METHODS: HIV-infected patients with PTB admitted to Shanghai Public Health Clinical Center from January 2011 to December 2015 were retrospectively enrolled. In this cohort, the survival prognosis was estimated by the Kaplan-Meier method, while univariate and multivariate Cox proportional hazards models were used to determine the risk factors affecting mortality. RESULTS: After reviewing 4914 admitted patients with HIV infection, 359 PTB cases were identified. At the time of PTB diagnosis, the patients' median CD4+ T cell count was 51 /mm3 (IQR: 23-116), and 27.30% of patients (98/359) were on combination antiretroviral therapy (cART). For the 333 cases included in the survival analysis, the overall mortality was 15.92% (53/333) during a median 27-month follow-up. The risk factors, including age older than 60 years (HR: 3.18; 95% CI: 1.66-6.10), complication with bacterial pneumonia (HR: 2.64; 95% CI: 1.30-5.35), diagnosis delay (HR: 2.60; 95% CI: 1.42-4.78), CD4+ T cell count less than 50/mm3 (HR: 2.38; 95% CI: 1.27-4.43) and pulmonary atelectasis (HR: 2.20; 95% CI: 1.05-4.60), might independently contribute to poor survival. Among patients without cART before anti-TB treatment, the later initiation of cART (more than 8 weeks after starting anti-TB treatment) was found to increase the mortality rate (OR: 4.33; 95% CI: 1.22-15.36), while the initiation of cART within 4-8 weeks after starting anti-TB treatment was associated with the fewest deaths (0/14). CONCLUSIONS: The subjects in this study conducted in the cART era were still characterized by depressed immunological competence and low rates of cART administration, revealing possible intervention targets for preventing TB reactivation in HIV-infected individuals under current circumstances. Furthermore, our study indicated that the timely diagnosis of PTB, prevention of secondary bacterial pneumonia by prophylactic management and optimization of the timing of cART initiation could have significant impacts on decreasing mortality among HIV/PTB co-infected populations. These findings deserve further prospective investigations to optimize the management of HIV/PTB-co-infected patients. TRIAL REGISTRATION: NCT01344148 , Registered September 14, 2010.

The clinical and laboratory features of neurosyphilis in HIV-infected patients: A retrospective study in 92 patients.

Neurosyphilis (NS) is an important component of central nervous system diseases among HIV-infected patients. However, its characteristics are not very clear. A retrospective analysis of clinical and laboratory findings was performed in 92 NS patients with HIV infection from a tertiary hospital in Shanghai, China. The patients had a median age of 38 years and a median CD4 count of 198 cells/µL. In all, 44.6% (41/92) were diagnosed as asymptomatic NS (ANS), 23.9% (22/92) as syphilitic meningitis, 17.4% (16/92) as cerebrovascular NS, and 14.1% (13/92) as parenchymal syphilis. A quarter of patients (23/92) complicated with ocular syphilis (OS), 60.9% (14/23) of which were ANS. The serum tolulized red unheated serum test (TRUST) titers were ≤1:8 in 15 patients (16.3%), 1:16-1:128 in 51 patients (55.4%), and ≥1:256 in 26 patients (28.3%). Sixty-nine patients (75.0%) had both cerebrospinal fluid (CSF) TRUST and Treponema pallidum particle assay reactive. CSF pleocytosis and protein elevation were found in 58.7% and 53.3% of patients, respectively. Syphilitic meningitis was more likely to present with CSF pleocytosis than ANS (P = .001), cerebrovascular NS (P < .001), and parenchymal NS (P < .001). The proportion of patients with CSF elevated protein was lower in ANS group than that in syphilitic meningitis (P = .003), cerebrovascular NS (P = .001), and parenchymal NS groups (P = .025), and was higher in sero-TRUST titers ≤1:8 group than that in 1:16-1:128 (P = .01) and 1:256-1:1024 groups (P = .005).This study revealed that ANS was the most common clinical type of NS in HIV-infected patients, which should be considered in HIV and syphilis co-infection patients without neurologic symptoms, especially in those with OS. Different patterns of NS might have different CSF features which may also vary with sero-TRUST titers.

Serum TRSUT Titer ≥1: 16 Is a Predictor for Neurosyphilis Among HIV-Infected Patients With Concurrent Syphilis and No Neurological Symptoms.

Investigating the predictors for lumbar puncture to diagnose the asymptomatic neurosyphilis among HIV and syphilis co-infected patients in Shanghai, China. Respectively, screening the medical records from August 1, 2009 to June 30, 2015. Those HIV-infected patients with concurrent syphilis who had received lumbar puncture were selected and their clinical and demographic data were recorded. Participants comprised symptomatic and asymptomatic patients. The latter ones could be further divided into 3 groups: late syphilis, early syphilis with anti-syphilis treatment failure, and early syphilis with serum toludine red unheated serum test (TRUST) ≥1:32. Both syphilis stage and anti-syphilis treatment effect were defined by common criteria, and syphilis of unknown duration was considered as late syphilis. Asymptomatic neurosyphilis was defined as neurosyphilis without neurological symptoms such as headache, cognitive dysfunction, motor deficits, auditory or ophthalmic abnormalities, and stroke. Neurosyphilis was defined as reactive cerebrospinal fluid (CSF) TRUST and/or CSF white blood cell >20 cells/µL without other reasons. Mann-Whitney test and Fisher's exact test were used for analyzing the difference between neurosyphilis and non-neurosyphilis group. Logistic regression test was performed to analyze the risk factors for neurosyphilis. In total, 170 participants were collected, and the rate of neurosyphilis was 32.35%. Among all the 105 participants without neurological symptoms, 80 patients were with late syphilis and 25 were with early syphilis. Among the early syphilis patients, 23 had a TRUST ≥1:32 and the other 2 experienced an anti-syphilis treatment failure. The differences of clinical and demographic variables between neurosyphilis and non-neurosyphilis group were not statistically significant except the serum TRUST titer (P < 0.01). From HIV/syphilis co-infected patients with or without neurological symptom, those who had neurological symptoms, CD4 <350 per µL and serological TRUST titer ≥1:16 were 4.9-fold (95% confidence interval [CI]: 2.37-10.31), 4.3-fold (95% CI: 1.17-15.78), and 4.1-fold (95% CI: 1.58-10.76), respectively, more likely to be diagnosed with neurosyphilis. Asymptomatic patients whose serum TRUST titer ≥1:16 were 8.48-fold (95% CI: 1.08-66.63) more likely to have asymptomatic neurosyphilis. Among asymptomatic HIV-infected patients with late syphilis or early syphilis experienced an anti-syphilis treatment failure, those who have a serum TRUST titer ≥1:16 are suggested to perform lumbar puncture in order to avoid delayed diagnosis and the occurrence of severe sequelae of syphilis.

[Proteomic study on effect of tangcao pill on microsome CYP450].

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].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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(-).

Clinical findings in 111 cases of influenza A (H7N9) virus infection.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Penicillium marneffei chylous ascites in acquired immune deficiency syndrome: a case report.

Penicillium marneffei (P. marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involvement. However, no cases of P. marneffei infection with chylous ascites have been reported thus far. In this report, we describe the first case of acquired immune deficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with amphotericin B for 3 mo, while receiving concomitant therapy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 mo. P. marneffei should be considered in the differential diagnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with P. marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.

[Molecular mechanisms of fluconazole resistance in clinical isolates of Candida glabrata].

OBJECTIVE: To determine if changes in the levels of expression of ERG11, CDR1 and CDR2 genes could be associated with resistance phenotype in clinical isolates of Candida glabrata (C. glabrata). METHODS: We used quantitative RT-PCR analysis to evaluate the expression of the ERG11, CDR1 and CDR2 genes in clinical isolates including 9 fluconazole-resistant, 9 fluconazole-susceptible dose dependent (S-DD) and 10 fluconazole-sensitive C. glabrata isolates. RESULTS: In the fluconazole-resistant isolates, the S-DD isolates and the fluconazole-sensitive isolates, the levels of expression of ERG11 gene were 121.4 +/- 96.8, 102.9 +/- 78.8, 51.2 +/- 20.7, respectively; the levels of expression of CDR1 gene were 3.1 +/- 1.4, 1.9 +/- 0.7, 1.1 +/- 0.4, respectively; the levels of expression of CDR2 gene were 3.7 +/- 2.2, 3.4 +/- 2.4, 1.9 +/- 0.9, respectively. Quantitative RT-PCR analyses revealed that the fluconazole-resistant isolates expressed ERG11 at higher levels than fluconazole-sensitive isolates (P = 0.041). CDR1 expression was significantly higher in the fluconazole-resistant isolates as compared with that in the fluconazole-sensitive isolates (P < 0.001) and the expression was also significantly higher in the S-DD isolates as compared with that in the fluconazole-sensitive isolates (P = 0.009). CDR2 upregulation was observed in the fluconazole-resistant isolates as compared with the susceptible isolates (P = 0.018). With the decrease of susceptibility to fluconazole, the levels of expression of ERG11, CDR1 and CDR2 genes in the isolates appeared to be increased. CONCLUSIONS: These results provide evidence that the overexpression of ERG11, CDR1 and CDR2 genes is associated with the increase of fluconazole resistance in clinical isolates of C. glabrata. ERG11, CDR1 and CDR2 upregulation is a major molecular mechanism of fluconazole resistance in clinical isolates of C. glabrata.

[A cross-sectional survey of occult hepatitis B virus infection in HIV-infected patients].

OBJECTIVES: Occult HBV infection is defined by positive HBV DNA in individuals with undetectable levels of HBsAg. The objective of this study was to assess the prevalence of occult HBV infection in HIV-infected patients. METHODS: Serum samples were obtained from 105 HBsAg-negative HIV patients who were hospitalized and were not given anti-virus treatment at Shanghai Public Health Clinical Center. Microparticle enzyme immunoassay (MEIA) was used to detect HBV serologic markers (HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc). ELISA was used to detect HCV antibody. CD4+ T cell count was examined with flow cytometry. Nested PCR was used to amplify surface protein region of HBV. RESULTS: 32 (30.5%) patients (27 men, 5 women) were HBV DNA positive in the 105 HBsAg-negative HIV-infected patients (92 men and 13 women). 22 patients (including 5 patients with HBV DNA +) were in 16-30 years group, 44 patients (including 15 patients with HBV DNA +) were in 3149 years group and 39 patients (including 12 patients with HBV DNA +) were in 50-75 years group. 5 patients were negative for all HBV serologic markers and 27 patients detected with at least one of anti-HBc, anti-HBe or anti-HBs. 14 patients (29.8%) with HBV DNA + in 47 HIV-infected patients were coinfected with HCV, 18 patients (31.0%) were HBV DNA + in 58 HIV-monoinfected patients. The median absolute CD4+ T cell count was 145.1 cells/microl (4-623 cells/microl), 26 patients (34.7%) were HBV DNA + in 75 AIDS patients with CD4+ T cell <200 cells/microl and 6 patients (20.0%) HBV DNA + in 30 HIV-infected patients with CD4+ T cell >200 cells/microl. No statistical significant association could be established between the above factors. CONCLUSIONS: It is found that occult HBV did occur in HIV-infected patients. No statistical significant association could be established between occult HBV infection and gender, age, HBV serologic markers, coinfected HCV and CD4+ T cell count.

[Diagnosis and treatment of major protozoal infections among acquired immune deficiency syndrome patients].

Protozoal infection is one of the most important opportunistic infections among patients with acquired immune deficiency syndrome (AIDS). In order to enhance the knowledge of protozoal infections in AIDS, the current status of diagnosis and treatment of toxoplasmic encephalitis, cryptosporidiosis, microsporidiosis and isosporiasis was reviewed in this paper.

Invasive fungal infections among inpatients with acquired immune deficiency syndrome at a Chinese university hospital.

Invasive fungal infections (IFIs) have become a major cause of morbidity and mortality among people with acquired immune deficiency syndrome (AIDS), however, little is known about the clinical features and prognosis of IFI in AIDS in China. This study aimed to characterise the clinical features and prognosis of IFI in AIDS patients in China. We retrospectively reviewed the records of all HIV-infected patients at a Chinese university hospital between December 2004 and May 2006. We identified 35 patients with IFI. IFIs included thrush, oesophageal candidiasis, fungal pneumonia, cryptococcosis, penicilliosis and fungaemia, 44.4% of IFIs occurred in the digestive tract, 71.8% of IFIs occurred in patients with CD4(+)T-lymphocyte counts <100 cells mm(-3). Candida albicans accounted for 57.4% of fungal pathogens isolated. All the patients received both antiretroviral and antifungal therapy; 27 patients were cured and eight died. IFI is one of the most common opportunistic infections in AIDS patients in China. IFIs mainly occur in patients with low CD4(+)T-lymphocyte counts. The majority of IFIs occur in the digestive tract. The most common pathogen causing IFI is C. albicans. The mortality rate remains high although antiretroviral therapy and many newer antifungals are available in China.