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.

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.

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.

[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.

Measles virus infection in adults induces production of IL-10 and is associated with increased CD4+ CD25+ regulatory T cells.

Despite steady progress in elimination of measles virus globally, measles infection still causes 500,000 annual deaths, mostly in developing countries where endemic measles strains still circulate. Many adults are infected every year in China, with symptoms more severe than those observed in children. In this study, we have used blood samples from adult measles patients in Shanghai and age-matched healthy controls to gain an understanding of the immune status of adult measles patients. IFN-alpha mRNA was reduced in patient PBMC compared with healthy controls. In contrast, gene expression and plasma production of IL-2, IL-10, and IFN-gamma were elevated in patient blood. A similar cytokine profile was observed at early times when cultured PBMC were infected with a clinical isolate of measles virus. In contrast to previous studies in pediatric patients, we did not find a reduction in total CD4(+) and CD8(+) T cells in patient PBMC. Interestingly, we found that CD4(+)CD25(+)CD127(low) regulatory T cells were significantly increased in patient PBMC compared with controls. Using intracellular cytokine staining we also show that the measles virus induces IL-10-producing CD14(+) and CD4(+)CD25(+) cells in PBMC. Our results show that adult measles patients in the acute phase of the disease have a mixed Th1/Th2 type response, accompanied with severe immunosuppression of both innate and adaptive responses including suppression of type I IFN. Both regulatory T cells and plasma IL-10 may contribute to the immunosuppression.

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.