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Objective:To assess the efficacy and safety of trimethoprim/sulfamethoxazole (TMP/SMZ) combined with caspofungin for the treatment of acquired immunodeficiency syndrome (AIDS)patients with moderate to severe pneumocystis pneumonia (PCP) requiring mechanical ventilation.Methods:The clinical data of AIDS patients who admitted to Chongqing Public Health Medical Center from March 1, 2019 to March 1, 2021 with moderate to severe PCP requiring mechanical ventilation were retrospectively analyzed. Clinical characteristics and outcomes were compared between two groups receiving either combination therapy with TMP/SMZ and caspofungin (combination therapy group) or TMP/SMZ monotherapy (monotherapy group). The patients were divided into two subgroups according to the baseline arterial partial pressure of oxygen (PaO 2), patients with arterial PaO 2≥50 mmHg (1 mmHg=0.133 kPa) and PaO 2 <50 mmHg. The clinical efficacies of combination therapy and monotherapy in each subgroup were further compared. Chi-square and Fisher exact test were used for statistical analysis. The three-month survival was estimated by the Kaplan-Meier method, and the three-month survival rates were compared by Log-rank method. Results:A total of 83 patients were enrolled, including 23 in the monotherapy group and 60 in the combination therapy group. There was no significant difference in all-cause hospital mortalities between these two groups (34.8%(8/23) vs 23.3%(14/60), χ2=1.12, P=0.290). Kaplan-Meier survival curves indicated no significant difference in the three-month survival rates between the two groups ( χ2=0.51, P=0.477). There ware no significant differences observed in the positive clinical response rates and the mechanical ventilation rates after seven days of anti-PCP treatment between the two groups ( χ2=0.02 and 0.01, respectively, both P>0.05). In the 52 patients with PaO 2≥50 mmHg, no significant difference in all-cause hospital mortalities was observed between the monotherapy group and the combination therapy group (2/13 vs 25.6%(10/39), χ2=0.14, P=0.704). There was no statistical significance in the three-month survival rates between the two groups ( χ2=0.69, P=0.407). No significant difference was observed either in the clinical positive response rates or the mechanical ventilation rates after seven days of anti-PCP treatment between the two group( χ2=1.02 and 0.69, respectively, both P>0.05). In the 31 patients with PaO 2<50 mmHg, the all-cause hospital mortality in the combination therapy group was 19.0%(4/21), while six of the 10 patients in the monotherapy group died, and the difference was statistically significant (Fisher exact test, P=0.040). The three-month survival rate in the combination therapy group was significantly higher than that in the monotherapy group ( χ2=4.09, P=0.043). There were no significant differences in clinical positive response rate and the mechanical ventilation rate after seven days of anti-PCP treatment between the two group (Fisher exact test, both P>0.05). The overall adverse event rate in the monotherapy group was 87.0%(20/23), with an incidence of 56.5%(13/23) for both electrolyte disturbances and bone marrow suppression. The above incidences in the combination therapy group were 78.3%(47/60), 35.0%(21/60) and 53.3%(32/60), respectively, and all differences were not statistically significant ( χ2=0.34, 3.18 and 0.07, respectively, all P>0.05). Conclusions:The efficacy of combination therapy with TMP/SMZ and caspofungin is comparable to that of TMP/SMZ monotherapy in AIDS patients with moderate to severe PCP requiring mechanical ventilation. However, in AIDS patients with PCP requiring mechanical ventilation with the baseline PaO 2<50 mmHg, the efficacy of combination therapy is statistically superior to that of TMP/SMZ monotherapy. Combination therapy does not increase the risk of adverse events.
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Matrix protein p17 is a structural protein of human immunodeficiency virus(HIV). It not only plays a key role in multiple stages of HIV life cycle,but also is closely associated with HIV-related lymphoma,neurocognitive impairment and breast cancer. This article reviews the role of matrix protein p17 in HIV infection and HIV-related diseases.
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Objective:To investigate the influence of hepatitis B virus (HBV) combined with human immunodeficiency virus (HIV) infection on the efficacy of anti-retroviral therapy (ART).Methods:The data of 269 HIV-infected patients treated in Chongqing Public Health Medical Center from September 2016 to October 2019 were collected. The patients were divided into HIV monoinfection group and HIV/HBV coinfection group. The changes in liver function, CD4 + T lymphocyte count, and HIV RNA level between the two groups were compared when ART started and at different time points (2, 4, 8, 12, 24, 36, 48, and 96 weeks) after ART started. Statistical analysis were performed by independent sample t test, rank sum test and chi-square test. Results:A total of 145 patients with HIV monoinfection and 124 patients with HIV/HBV coinfection were collected. There were no statistically significant differences in liver function indexes (aspartate aminotransferase ( t=9.566), alanine aminotransferase ( t=-4.652) and total bilirubin ( t=-25.476)) between the two groups of patients when ART started (all P>0.05). At 24, 48 and 96 weeks after ART, the CD4 + T lymphocyte counts in the HIV monoinfection group and the HIV/HBV coinfection group were (305.9±156.9)/μL vs (266.2±172.5)/μL, (388.5±226.1)/μL vs (380.8±287.4)/μL and (369.5±191.4)/μL vs (453.6±179.6)/μL, respectively. At 48, 72 and 96 weeks after ART, the CD4 + T lymphocyte count increasing values were 121.0(-52.5, 144.5)/μL vs 156.0(-35.8, 185.8)/μL, 139.0(-116.0, 176.8)/μL vs 114.5(-59.5, 229.0)/μL and -91.0(-110.0, 153.3)/μL vs -94.0(-130.8, 114.3)/μL, respectively. The differences were all not statistically significant ( t=-0.516, -0.066 and -1.414, Z=-1.715、-0.802 and -1.602, respectively, all P>0.05). At 24, 48, and 96 weeks after ART, the HIV RNA inhibition rates in the HIV monoinfection group were 89.7%(130/145), 96.6%(140/145), and 96.6%(140/145), respectively, and those in the HIV/HBV coinfection group were 87.1%(108/124), 92.7%(115/124) and 94.4%(117/124), respectively. The differences were all not statistically significant ( χ2=0.026, 0.053 and 0.017, respectively, all P>0.05). In the second and fourth weeks after ART, the abnormal liver function rates of the HIV monoinfection group were 3.4%(5/145) and 6.2%(9/145), respectively, which were lower than those in the HIV/HBV coinfection group (21.0%(26/124) and 13.7%(17/124), respectively). The differences were both statistically significant ( χ2=20.121 and 4.309, respectively, both P<0.05). However, the abnormal liver function rates in the two group in the 8th week after ART were 10.3%(15/145) and 9.7%(12/124), respectively, and those in the 12th week were 9.0%(13/145) and 9.7%(12/124), respectively, and those in the 24th week were 9.7%(14/145) and 8.9%(11/124), respectively, and those in the 36th week were 9.7%(14/145) and 10.5%(13/124), respectively, and those in the 48th week were 8.3%(12/145) and 8.1%(10/124), respectively, and those in the 96th week were 2.8%(4/145) and 0(0/124), respectively. The differences were all not statistically significant ( χ2=0.330, 0.040, 0.049, 0.051, 0.004 and 3.472, respectively, all P>0.05). Conclusion:HBV coinfection has no adverse effect on the ART effect of HIV-infected patients.
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A novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has been pandemic worldwide. The genetic dynamics of quasispecies afford RNA viruses a great fitness on cell tropism and host range. However, no quasispecies data of SARS-CoV-2 have been reported yet. To explore quasispecies haplotypes and its transmission characteristics, we carried out single-molecule real-time (SMRT) sequencing of the full-length of SARS-CoV-2 spike gene within 14 RNA samples from 2 infection clusters, covering first-to third-generation infected-patients. We observed a special quasispecies structure of SARS-CoV-2 (modeled as One-King): one dominant haplotype (mean abundance ~70.15%) followed by numerous minor haplotypes (mean abundance < 0.10%). We not only discovered a novel dominant haplotype of F1040 but also realized that minor quasispecies were also worthy of attention. Notably, some minor haplotypes (like F1040 and currently pandemic one G614) could potentially reveal adaptive and converse into the dominant one. However, minor haplotypes exhibited a high transmission bottleneck (~6% could be stably transmitted), and the new adaptive/dominant haplotypes were likely originated from genetic variations within a host rather than transmission. The evolutionary rate was estimated as 2.68-3.86 x 10-3 per site per year, which was larger than the estimation at consensus genome level. The One-King model and conversion event expanded our understanding of the genetic dynamics of SARS-CoV-2, and explained the incomprehensible phenomenon at the consensus genome level, such as limited cumulative mutations and low evolutionary rate. Moreover, our findings suggested the epidemic strains may be multi-host origin and future traceability would face huge difficulties.
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BackgroundA pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading over the world. However, the viral dynamics, host serologic responses, and their associations with clinical manifestations, have not been well described in prospective cohort. MethodsWe conducted a prospective cohort and enrolled 67 COVID-19 patients admitting between Jan 26 and Feb 5, 2020. Clinical specimens including nasopharyngeal swab, sputum, blood, urine and stool were tested periodically according to standardized case report form with final follow-up on February 27. The routes and duration of viral shedding, antibody response, and their associations with disease severity and clinical manifestations were systematically evaluated. Coronaviral particles in clinical specimens were observed by transmission electron microscopy (TEM). ResultsThe median duration of SARS-CoV-2 RNA shedding were 12 (3-38), 19 (5-37), and 18 (7-26) days in nasopharyngeal swabs, sputum and stools, respectively. Only 13 urines (5.6%) and 12 plasmas (5.7%) were viral positive. Prolonged viral shedding was observed in severe patients than that of non-severe patients. Cough but not fever, aligned with viral shedding in clinical respiratory specimens, meanwhile the positive stool-RNA appeared to align with the proportion who concurrently had cough and sputum production, but not diarrhea. Typical coronaviral particles could be found directly in sputum by TEM. The anti-nucleocapsid-protein IgM started on day 7 and positive rate peaked on day 28, while that of IgG was on day 10 and day 49 after illness onset. IgM and IgG appear earlier, and their titers are significantly higher in severe patients than non-severe patients (p<0.05). The weak responders for IgG had a significantly higher viral clearance rate than that of strong responders (p= 0.011). ConclusionsNasopharyngeal, sputum and stools rather than blood and urine, were the major shedding routes for SARS-CoV-2, and meanwhile sputum had a prolonged viral shedding. Symptom cough seems to be aligned with viral shedding in clinical respiratory and fecal specimens. Stronger antibody response was associated with delayed viral clearance and disease severity. Summary boxesO_ST_ABSWhat is already known on this topicC_ST_ABSAs a newly appearing infectious disease, early efforts have focused on virus identification, describing the epidemiologic characteristics, clinical course, prognostics for critically illed cases and mortality. Among COVID-19 cases reported in mainland China (72 314 cases, updated through February 11, 2020), 81% are mild, 14% are severe, and 5% are critical. The estimated overall case fatality rate (CFR) is 2.3%. Some case series reported had shown that SARS-CoV-2 could shed in upper/lower respiratory specimens, stools, blood and urines of patients. However, important knowledge gaps remain, particularly regarding full kinetics of viral shedding and host serologic responses in association with clinical manifestations and host factors. What this study addsThe incubation period has no change after spreading out of Wuhan, and has no sex or age differences, however, children had prolonged incubation period. Due to early recognition and intervention, COVID-19 illness of Chongqing cohort is milder than that of Wuhan patients reported. This prospective cohort study on SARS-CoV-2 infection shows clearly that the viral and serological kinetics were related in duration of infection, disease severity, and clinical manifestations of COVID-19. Our data demonstrate that nasopharyngeal, sputum and stools are major shedding routes for SARS-CoV-2, and stronger NP antibody response is associated with delayed viral clearance and disease severity.
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Objective:To investigate the features of chest computed tomography (CT) imaging and dynamic changes of severe corona virus disease 2019 (COVID-19).Methods:The clinical and CT data of 17 patients diagnosed with severe COVID-19 admitted to Chongqing Public Health Medical Center from January 24 to February 6, 2020 were collected. The first chest CT manifestations and the dynamic changes of imaging during treatment were retrospectively analyzed.Results:The first chest CT manifestations of the 17 patients showed that 16 cases presented with peripheral and subpleural distributions, and two cases presented with three lobes involved, one case with four lobes involved and 14 cases with five lobes involved, and 17 cases presented with ground-glass opacities, ten cases with consolidation, seven cases with subpleural line, nine cases with air bronchogram, three cases with thickened lobular septum, two cases with bronchiectasis, two cases with pleural effusion, three cases with lymphadenopathy with the short diameter of 1.0-1.2 cm.Among 16 patients who underwent repeated CT examination, the lesions of eight patients showed continuous improvement, and those of the other eight patients showed fluctuating changes.Conclusions:The CT findings of severe COVID-19 patients are mainly ground-glass opacities and consolidation, with the peripheral distribution. The range of lesions is wide, with five-lobe involvement mostly. Lymphadenopathy or pleural effusion is rare. Pynamic monitoring chest CT is useful for the evaluation for the therapeutic effects.
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Objective@#To investigate the features of chest CT imaging and dynamic changes of severe coronavirus disease 2019 (COVID-19).@*Methods@#The clinical and computed tomography (CT) data of 17 patients diagnosed with severe COVID-19 admitted to Chongqing Public Health Medical Center from January 24 to February 6, 2020 were collected. The first chest CT manifestations and the dynamic changes of imaging during treatment were retrospectively analyzed.@*Results@#The first chest CT manifestations of the 17 patients showed that 16 cases presented with peripheral and subpleural distributions, and 2 cases presented with 3 lobes involved, one case with 4 lobes involved and 14 cases with 5 lobes involved, and 17 cases presented with ground-glass opacities, ten cases with consolidation, seven cases with subpleural line, nine cases with air bronchogram, 3 cases with thickened lobular septum, two cases with bronchiectasis, two cases with pleural effusion, two cases with lymphadenopathy with the short diameter of 1.0-1.2cm. Among 16 patients who underwent repeated CT examination, the lesions of 8 patients showed continuous improvement, and those of the other 8 patients showed fluctuating changes.@*Conclusions@#The CT findings of severe COVID-19 patients are mainly ground-glass opacities and consolidation, with the peripheral distribution. The range of lesions is wide, with 5-lobe involvement mostly. Lymphadenopathy or pleural effusion is rare. Chest CT is useful for the evaluation for the therapeutic effects.
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Objective To describe the disease spectrum,morbidity,mortality and prognostic factors of acquired immune deficiency syndrome (AIDS) patients complicated with central nervous system (CNS) infections.Methods The data of 4 426 AIDS patients from February 2013 to February 2017 in Chongqing public health medical center were collected,among which 499 cases had CNS infection.The morbidity and mortality of CNS infections were calculated.Association between different CNS infections and CD4+T cell counts was analyzed.Prognostic factors for the outcome of hospitalization were also studied.Mann-Whitney U test was used for continuous variables.Univariate and multivariate analyses were performed by logistic regression analysis.Results The morbidity of CNS infections in AIDS patients was 11.27% (499/4 426).The most prevalent CNS infections were tuberculous meningitis (4.50%),cryptococcal meningitis (3.25 %) and CNS infections with unknown etiology (1.11 %).The mortality rate was 18.84% (94/499),among which tuberculous meningitis accounted for 35 cases (17.59%),cryptococcal meningitis 23 cases (15.79%) and CNS infections with unknown etiology 19 cases (38.76%).The average CD4-T cell count level in those who died were significantly lower than that in those who survived (Z=2.51,P =0.001).Visual impairment,nuchal rigidity,positive pathologic reflexes,consciousness disturbance,CD4+T cell counts<50 cells/μL and HIV RNA≥5 lg copies/mL at baseline were independent prognostic factors for mortality.Conclusions The morbidity and mortality of CNS infections are high among AIDS patients in Chongqing,and those patients with severe immunosuppression are usually affected.Older age,consciousness disturtance and severe immunosuppression are three independent risk factors for mortality.
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Objective To compare the clinical characteristics and outcomes of bacterial and fungal bloodstream infections in the patients with acquired immunodeficiency syndrome (AIDS). Methods The clinical data of AIDS patients complicated with bacterial or fungal bloodstream infection treated in Chongqing Public Health Medical Center from January 2016 to June 2018 were analyzed retrospectively. The two groups of patients were compared in terms of clinical symptoms, laboratory tests and outcomes. Results Significantly more patients in bacterial group (AIDS complicated with bacterial bloodstream infection) were associated with intravenous drug abuse than that in fungal group (AIDS complicated with fungal bloodstream infection) (P<0.05). The average age of patients was older in bacterial group than in fungal group. The incidence of nausea, vomiting and skin rash in fungal group was significantly higher than that in bacterial group (P<0.05). CD4+T cells in fungal group decreased more significantly than that in bacterial group. No significant difference was found between the two groups in sex ratio, routine blood tests, biochemical assays, and mortality. Conclusions Fungi are the main pathogen of AIDS-associated bloodstream infections. Contrast to the bacterial bloodstream infections in AIDS patients, fungal bloodstream infection is more frequently found in younger patients, and associated with higher incidence of nausea, vomiting, typical skin rash, and more remarkable decrease of CD4+T cells. Bacterial bloodstream infection is more prevalent than fungal bloodstream infection in intravenous drug abusers. No significant difference is found in the mortality between the AIDS patients complicated with bacterial bloodstream infection and those complicated with fungal bloodstream infection.
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Cryptococcus neoformans meningitis is one of the most common opportunistic infections and causes of death in acquired immunodeficiency syndrome(AIDS)patients with HIV infection. Comprehensive treatment is the key to reduce the mortality rate of AIDS patients with Cryptococcus neoformans meningitis,which includes antifungal treatment, antiretroviral therapy and intracranial pressure management.This article reviews the current status and advanced of comprehensive therapy for Cryptococcus neoformans meningitis in AIDS patients.
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Objective To explore the mortality and prognostic factors of cryptococcal meningitis (CM) in patients with acquired immunodeficiency syndrome (AIDS).Methods We collected the clinical data of all the 203 AIDS patients complicated with CM who had been treated between December 2010 and March 2017 in Chongqing Public Health Medical Center.They were followed up by telephone periodically after hospital discharge and their survival or death was recorded.Their overall mortality rate,survival curves and prognostic factors were then analyzed.Results Of the 203 cases included in this study,92.6% had CD4+ T cell counts ≤100 cells/μL,50.3% HIV RNA>5 lg copies/mL,and 64.5% intracranial pressure ≥250 mmH2O.Their mortality during hospital stay was 9.9%(20/203),mortality during follow-up 16.2% (24/148) and overall mortality 26.1%.Their survival rate declined rapidly during the first 2 weeks after disease onset,and their accumulated mortality was close to 25.0% at week 10 but stabilized thereafter.The patients aged between 18 and 44 years had a significantly lower risk of death than those of other age groups,showing that age was an independent protective prognostic factor (AOR=0.228,P=0.036,95%CI:0.057~0.910).Consciousness disorder was an independent risk factor for death (AOR=7.001,P=0.035,95% CI:1.143~42.882).Conclusions AIDS patients complicated with CM may face a high mortality and death may mostly occur within the first 3 months after disease onset.Those with a younger age may have relatively better prognosis.Consciousness disorder is a risk factor of death.