Risk factors associated with low-level viremia in human immunodeficiency virus/acquired immunodeficiency syndrome patients after anti-retroviral therapy / 中华传染病杂志

Objective:To investigate the risk factors of low-level viremia (LLV) among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients after combined anti-retroviral therapy (ART), and to provide evidence for reducing the risk of LLV.Methods:It was a cross-sectional observation study that enrolled HIV/AIDS patients with LLV (plasma HIV-1 RNA was 50 to 1 000 copies/mL) receiving ART over one year (LLV group) from January 2019 to December 2020 in Guangzhou Eighth People′s Hospital, Guangzhou Medical University. Contemporaneous patients with ART over one year and successful viral suppression (plasma HIV-1 RNA<50 copies/mL) were randomly selected as the control group (suppression group) with a ratio of 1∶2.5, and the risk factors for LLV were analyzed by unconditional logistic regression.Results:A total of 128 and 297 patients were enrolled in LLV group and the suppression group, respectively.ART durations were 3.62(1.83, 4.89) years and 4.91(2.90, 5.88) years, respectively. Multivariate logistic regression analysis showed that the risk factors associated with LLV included the age of initial ART treatment above 50 years old (odds ratio ( OR)=1.82, 95% confidence interval ( CI) 1.01 to 3.26, P=0.046), the baseline HIV-1 RNA over 1×10 5 copies/mL ( OR=2.18, 95% CI 1.30 to 3.68, P=0.003), using the simplified initial ART regimen ( OR=1.82, 95% CI 1.02 to 3.26, P=0.044), missing medication more than three times per year ( OR=2.49, 95% CI 1.55 to 4.01, P<0.001) and changing regimen during ART ( OR=1.90, 95% CI 1.14 to 3.14, P=0.013), while the duration of ART longer than five years could reduce the risk of LLV ( OR=0.37, 95% CI 0.22 to 0.64, P<0.001). In patients with simplified initial ART regimen, the baseline CD4 + T lymphocyte count of whom with LLV was lower than that of whom with viral suppression, and the difference was statistically significant (94.00 (24.00, 281.00)/μL vs 375.00 (310.00, 435.00)/μL, Z=-2.60, P<0.001). Conclusions:The occurrence of LLV is related to the age of initial ART treatment, the baseline HIV-1 RNA, the initial ART regimen, the medication adherence and the change of ART regimen during ART. Strategies may be beneficial to reducing the risk of LLV for HIV/AIDS patients, such as initiating ART as soon as possible, using simplified regimen as initial regimen with caution in patients with low baseline CD4 + T lymphocyte counts, strengthening compliance education, avoiding unnecessary ART regimen changes.

Naturally occurring resistance-associated variants to NS3/4A protease and NS5A inhibitors in patients with HIV/HCV co-infection or HCV infection alone / 临床肝胆病杂志

Objective To investigate the difference in naturally occurring resistance-associated variants (RAVs) between the patients with HIV/HCV co-infection and those with HCV infection alone by detecting the drug resistance loci associated with HCV NS3/4A protease and NS5A inhibitors. Methods A total of 246 patients with HIV/HCV co-infection or HCV infection alone who were hospitalized or attended the outpatient service in Guangzhou Eighth People's Hospital, Guangzhou Medical University, from January 2016 to January 2020 were enrolled in this study. Serum samples were collected and next-generation sequencing (Illumina platform, PE250) was used for sequencing. The two groups of patients were compared in terms of RAVs associated with NS3/4A protease and NS5A inhibitors approved in China, and the drugs for analysis included asunaprevir/daclatasvir (ASV/DCV) and elbasvir/grazoprevir (EBR/GZR) for HCV genotype 1b and glecaprevir/pibrentasvir (GLE/PIB) for pan-genotypes. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results Among the 246 serum samples included in this study, 239 samples (97.2%) were successfully amplified by PCR and sequenced, with 102 samples from the patients with HIV/HCV co-infection and 137 from the patients with HCV infection alone. The analysis of RAVs associated with ASV/DCV and EBR/GZR showed that Y56F, Q80K/L, and S122N/R/T associated with ASV and GZR and L31M and Y93H associated with DCV and EBR were observed in patients with HIV/HCV (genotype 1b) co-infection or HCV (genotype 1b) infection alone; 2 patients with HIV/HCV co-infection had the RAVs of Y56F+Y93H associated with EBR/GZR, and 2 with HCV infection alone had the RAVs of Q80L+L31M and Y56F+Y93H, respectively, associated with EBR/GZR, with no significant difference in RAVs between the two groups (both P > 0.05). The analysis of RAVs associated with GLE/PIB for pan-genotypes showed that 3 patients with PIB-associated Y93H RAV were observed among the patients with HCV genotype 3a infection, among whom 2 had HIV/HCV co-infection and 1 had HCV infection alone ( P =0.590), and in addition, no RAVs associated with GLE/PIB were observed. Conclusion There is no significant difference in naturally occurring RAVs associated with HCV NS3/4A protease and NS5A inhibitors between the patients with HIV/HCV co-infection and those with HCV infection alone.

Clinical features of patients with severe dengue in Guangdong Province from 2013 to 2019 / 中华传染病杂志

Objective:To analyze the clinical features of patients with severe dengue (SD) in Guangdong Province, and to improve the understanding of the diagnosis and treatment of SD in China.Methods:The clinical data, laboratory examination and etiological test results of 257 SD cases from 29 dengue fever designated hospitals in Guangdong Province from January 1, 2013 to December 31, 2019 were respectively collected. The relevant indicators of the criteria for severe organ involvement were quantified. Logistic regression analysis was performed to analyze the risk factors for the development of multiple organ failure in SD patients.Results:Among the 257 SD patients, age was (64.1±20.1) years old, with 65.4%(168/257) of them ≥60 years old, 142 were male and 115 were female. One hundred and fifty-two (59.1%) patients had underlying conditions, including 115(44.7%) patients with hypertension. The clinical manifestations were mainly fever (98.4%(253/257)), fatigue (70.0%(180/257)), cough or expectoration (44.4%(114/257)), lethargy or irritability (39.3%(101/257)), vomiting (30.4%(78/257)), abdominal pain or tenderness (20.6%(53/257)), hepatomegaly (2.3%(6/257)), bleeding tendency (59.5%(153/257)), and pleural effusion or ascites (43.6%(112/257)). Platelet count levels were decreased in 90.9%(231/254) of the cases, and 97.1%(234/241) of patients had normal or decreased hematocrit. The most common of severe manifestations were severe organ involvement (61.1%(157/257)), followed by severe bleeding (37.0%(95/257)) and severe plasma leakage (30.0%(77/257)). Severe organ involvements were more common in the kidney (27.6%(71/257)) and heart (26.8%(69/257)). Multivariate logistic regression analysis showed that age (odds ratio ( OR)=1.051, 95% confidence interval ( CI) 1.004 to 1.100, P=0.035), hypertension ( OR=5.224, 95% CI 1.272 to 21.462, P=0.022), elevated aspartate aminotransferase (AST) level ( OR=1.002, 95% CI 1.001 to 1.003, P=0.001), blood urea nitrogen (BUN) ( OR=1.050, 95% CI 1.005 to 1.098, P=0.030), and international normalized ratio (INR) ( OR=4.604, 95% CI 1.601 to 13.238, P=0.005) were risk factors for the development of multiple organ failure in SD patients. The detection results of serum samples form 113 SD patients in acute phase showed that dengue virus (DENV)-1 accounted for 89.4%(101/113), DENV-2 accounted for 9.7%(11/113), and DENV-3 accounted for 0.9% (1/113). Conclusions:Elderly and those with co-existing conditions such as hypertension in SD patients in Guangdong Province are more common. Severe organ involvement such as kidney and heart is the main cause of SD. DENV-1 infection is predominant. Significant elevated levels of AST, BUN and INR may be related to a poor prognosis.

Clinical efficacy of ventriculo-peritoneal shunt in the treatment of acquired immunodeficiency syndrome complicated with cryptococcal neoformans meningitis / 中华传染病杂志

Objective:To investigate the clinical efficacy of ventriculo-peritoneal shunt (VPS) in acquired immunodeficiency syndrome (AIDS) patients with cryptococcal neoformans meningitis (CNM).Methods:Patients with AIDS and CNM who were hospitalized in Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 2015 to June 2020 were included and divided into VPS group and conventional treatment group.The data including symptoms and signs of meningitis, cerebrospinal fluid (CSF) pressure, CSF routine examination, ink staining, Cryptococcus culture and Cryptococcus culture negative time were obtained, and the clinical efficacy compared between the two groups after six and 48 weeks of treatment.Two independent samples t test or chi-square test was used for statistical analysis. Results:Among 66 AIDS patients with CNM, 26 cases in VPS group were (35.7±11.9) years, and 11 cases (42.3%) had CSF pressure> 330 mmH 2O (1 mmH 2O=0.009 8 kPa) at admission, 25 cases (96.2%) were positive for ink staining, and 20 cases (76.9%) had positive culture of Cryptococcus neoformans in CSF. There were 40 cases in the conventional treatment group with age of (38.9±12.9) years, 15 cases (37.5%) had CSF pressure>330 mmH 2O, 32 cases (80.0%) were positive for ink staining, and 31 cases (77.5%) were positive for culture of Cryptococcus neoformans in CSF. There were no significant differences of age, the proportion of patients with CSF pressure>330 mmH 2O, positive rate of ink staining, positive rate of Cryptococcus culture between the two groups ( t=-1.02, χ2=0.15, 3.49 and 0.00, respectively; all P>0.050). All patients were administrated with antifungal treatment, decreasing CSF pressure treatment, nutritional support and symptomatic treatment after admission. VPS was performed in patients with poor responses after medical conservative treatment in VPS group. At week six of treatment, the recovery rate of CSF pressure in VPS group was 57.7%(15/26), and the partial remission rate was 73.1%(19/26), which were both higher than those in conventional treatment group (31.0%(9/29) and 47.5%(19/40), respectively). The differences were both statistically significant ( χ2=3.96 and 4.22, respectively, both P<0.050). At week 48 of treatment, the recovery rate of CSF pressure in VPS group was 92.3%(24/26), the negative rate of Cryptococcus culture in CSF was 100.0%(20/20), and the complete remission rate was 46.2%(12/26), which were all higher than those in conventional treatment group (37.9%(11/29), 67.7%(21/31) and 20.0%(8/40), respectively). The differences were all statistically significant ( χ2=17.52, 8.03 and 5.10, respectively, all P<0.050). In VPS group, 22 cases were complete or partial remission, four cases were ineffective, and no death occurred, while there were 23 cases of complete or partial remission, 12 cases of ineffective and five cases of death in the conventional treatment group. The proportion of ineffective or death in the VPS group was 15.4%(4/26), which was lower than 42.5%(17/40) in the conventional treatment group. The difference was statistically significant ( χ2=5.34, P=0.021). Conclusions:VPS in AIDS patients with CNM could significantly improve the treatment outcomes, and reduce the rates of treatment failure and mortality.

Impact of low level viremia on the antiviral effect of human immunodeficiency virus/acquired immunodeficiency syndrome patients received anti-retroviral therapy / 中华传染病杂志

Objective:To investigate the impact of low level viremia (LLV) on the prognosis of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients received anti-retroviral therapy (ART).Methods:From January to December 2015, the HIV/AIDS patients with LLV received ART over one year were recruited in Guangzhou Eighth People′s Hospital, Guangzhou Medical University (LLV group). Patients with viral load (VL) less than 50 copies/mL were matched at ratio of 1∶1 according to gender, age and the transmission route were included in the control group (suppression group). The LLV group was divided into three subgroups according to VL (LLV-1 subgroup was 50-200 copies/mL, LLV-2 subgroup was 201-400 copies/mL, and LLV-3 subgroup was 401-1 000 copies/mL). The influence of LLV on the antiviral response during the following three years was investigated.The Wilcoxon signed rank test, Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:One hundred and thirty-seven patients were enrolled in the LLV group, of whom 111 were males and 26 were females, with age of (39.5±13.5) years old. At the same time, 137 patients were included in the suppression group. There were 93 cases in LLV-1 subgroup, 25 cases in LLV-2 subgroup and 19 cases in LLV-3 subgroup. There were no significant differences in the CD4 + T lymphocyte counts and CD4 + /CD8 + T lymphocyte counts ratios between LLV group and suppression group before ART (both P>0.05). During the three-year follow-up, the cumulative number of viral failures in LLV group (7.3%(10/137)) was significantly higher than that in the suppression group (1.5%(2/137)) ( χ2=5.578, P=0.018). Virological failure occurred in eight patients (8.6%) in the LLV-1 subgroup, two patients (8.0%) in the LLV-2 subgroup, and no patients in the LLV-3 subgroup. There was no statistical significance in the incidence of virological failure among all the subgroups ( P>0.05). At one, two, three years follow-up, the CD4 + T lymphocyte counts increased in both LLV group and suppression group without statistical differences (all P>0.05), and the CD4 + /CD8 + T lymphocyte counts ratios in each LLV group were lower than that in the suppression group ( Z=-3.183, -2.094 and -2.312, respectively, all P<0.05). At one, two, three years follow-up, There were no significant differences in CD4 + /CD8 + T lymphocyte counts ratios among the LLV-1, LLV-2 and LLV-3 subgroups (all P>0.05). Conclusion:HIV/AIDS patients with LLV having received ART over one year are more likely to develop virological failure and delay the recovery of immune function, which requires early relevant interventions.

Clinical characteristics and pathogenic spectrum of pulmonary filamentous fungal infection in acquired immunodeficiency syndrome patients in Guangdong Province / 中华传染病杂志

Objective:To investigate the clinical characteristics and pathogen spectrum of acquired immunodeficiency syndrome (AIDS) patients complicated with pulmonary filamentous fungal infection in Guangdong Province, so as to provide evidences for improving the diagnosis and treatment.Methods:A total of 143 AIDS patients with pulmonary filamentous fungal infection hospitalized in Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 2016 to December 2018 were included. The filamentous fungi cultured in bronchoalveolar lavage fluid of these patients were identified with morphological and molecular biological methods. And their clinical characteristics were analyzed. Nonparametric Kruskal-Wallis H test and chi-square test were used for statistical analysis. Results:Among the 143 patients, 116(81.1%) had fever, 104(72.7%) had cough, 83(58.0%) had expectoration, and 59(41.3%) had anhelation. The CD4 + T lymphocyte count was 22.0(9.3, 60.8) cells/μL and 118(82.5%) cases were below 100.0 cells/μL. The white blood cell counts decreased in 52(36.4%) cases and increased in 18(12.6%) cases, anemia was found in 109(76.2%) cases, platelet count decreased in 29(20.3%) cases. Sixty-four (44.8%) cases were positive for galactomannan test. Chest computed tomography showed diffuse infection of both lungs in 114(79.7%) cases, miliary changes in 12(8.4%) cases, pleural effusion in 44(30.8%) cases, and enlargement of pleural and (or) mediastinal lymph nodes in 45(31.5%) cases. After receiving antifungal therapy, 124 (86.7%) cases were cured or improved, and 19 (13.3%) cases were discharged automatically or died of disease deterioration. Among the 143 strains of filamentous fungi, there were 56 strains of Aspergillus species pluralis (39.2%, including 24 strains of Aspergillus fumigatus), 37 strains of Talaromyces marneffei ( T. marneffei) (25.9%), 22 strains of Penicilium species pluralis (15.4%), and 28 strains of other genera of filamentous fungi (19.6%). The median CD4 + T lymphocyte counts in patients infected with Aspergillus species pluralis, T. marneffei, Penicilium species pluralis and other genera were 24.5, 15.0, 53.5 and 22.0 cells/μL, respectively, and the difference was statistically significant ( H=11.282, P=0.010). The proportions of AIDS patients with different pulmonary filamentous fungal infection of CD4 + T lymphocyte count ≤50.0 cells/μL in descending order were T. marneffei group (89.2%(33/37)), Aspergillus species pluralis group and other genera group (67.9%(38/56), 67.9%(19/28)), and Penicillium species pluralis group (54.5%(12/22)), and the difference was statistically significant ( χ2=9.296, P=0.026). Conclusions:The clinical manifestations of pulmonary filamentous fungal infection in AIDS patients in Guangdong Province are not specific. The pathogenic spectrum contains various genera, and T. marneffei and Aspergillus fumigatus are dominant, which could be correlated with CD4 + T lymphocyte count.

Clinical features of acquired immunodeficiency syndrome patients complicated with peripulmonary occupational lesions / 中华传染病杂志

Objective:To analyze the clinical features of acquired immunodeficiency syndrome (AIDS) patients complicated with peripulmonary occupational lesions.Methods:Fifty-five AIDS patients with peripulmonary occupational lesions treated in Guangzhou Eighth People′s Hospital from January 2012 to January 2019 were included, and the clinical data of patients were retrospectively analyzed. According to the results of lung biopsy, the patients were divided into Mycobacterium infection group, fungal infection group and tumor group. The clinical characteristics, the proportion of different CD4 + T lymphocyte counts and chest computed tomography (CT) features of the three groups were compared. Chi square test was used for comparison among the three groups, and Bonferroni method was used to correct the test level for pairwise comparison. The significance level was 0.016 7 because of three pairwise comparisons. Results:Among 55 AIDS patients complicated with peripulmonary occupational lesions, pulmonary biopsy showed 14 cases with Mycobacterium infection, 12 cases with fungal infection and 15 cases with tumor lesions. Mixed diseases were found in 11 patients, including seven cases with Mycobacterium and fungus coinfection, four with tumor complicated with fungus and (or) Mycobacterium. Three with chronic interstitial pneumonia. The main clinical manifestations of 55 patients were fever, expectoration, fatigue, weight loss and superficial lymph node enlargement. There were no significant differences in symptoms/signs, white blood cell counts, hemoglobin levels, alanine transaminase and creatinine among Mycobacterium infection group, fungal infection group and tumor group (all P>0.05). There was significant difference in anti-retroviral therapy (ART) acceptance among the three groups ( χ2=15.165, P<0.01). However, the results of pairwise comparison between groups showed that there was significant difference between fungal infection group and tumor group ( χ2=7.514, P<0.016 7), while there was no significant difference between Mycobacterium infection group and tumor group, Mycobacterium infection group and fungal infection group ( χ2=0.255 and 5.306, respectively, both P>0.016 7). There were significant differences in clinical outcomes among the three groups ( χ2=15.119, P<0.01), and the pairwise comparison between the Mycobacterium infection group and the tumor group, and the fungal infection group and the tumor group showed significant differences ( χ2 =10.311 and 9.095, respectively, both P<0.016 7). The cases with CD4 + T lymphocyte count ≤50/μL, 51-<200/μL and ≥200/μL in Mycobacterium infection group were three cases, one case and 10 cases, respectively; those in fungal infection group were 10 cases, two cases and 0 case, respectively, and those in tumor group were one case, two cases and 12 cases, respectively. The difference was statistically significant ( χ2=21.284, P<0.01). Chest CT showed that there was significant difference in the types of space occupying lesions among the three groups ( χ2=13.308, P=0.003), and pairwise comparison between the two groups showed that there was significant difference between the Mycobacterium infection group and the tumor group ( χ2=11.312, P<0.016 7), while there were no significant differences between the Mycobacterium infection group and fungal infection group ( χ2=0.931, P>0.016 7), and the fungal infection group and the tumor group ( χ2=7.053, P>0.016 7). There was significant difference among the three groups in calcification focus ( χ2=8.524, P=0.004), while there was no difference between the Mycobacterium infection group and fungal infection+ tumor group ( χ2=10.982, P<0.016 7). Conclusions:Mycobacterium infection, fungal infection and tumor are the main types of peripulmonary occupational lesions in AIDS patients. The differential diagnosis could be made by combining with chest CT features, ART acceptance and CD4 + T lymphocyte level.

The efficacy and safety of lopinavir/ritonavir and arbidol in patients with coronavirus disease 2019 / 中华内科杂志

Objective:To evaluate the efficacy and safety of lopinavir/ritonavir (LPV/r) and arbidol in treating patients with coronavirus disease 2019 (COVID-19) in the real world.Methods:The clinical data of 178 patients diagnosed with COVID-19 admitted to Guangzhou Eighth People′s Hospital from January 20 to February 10, 2020 were retrospectively analyzed. According to patient′s antiviral treatment regimens, 178 patients were divided into 4 groups including LPV/r group (59 patients), arbidol group (36 patients), LPV/r plus arbidol combination group (25 patients) and the supportive care group without any antiviral treatment (58 patients). The primary end point was the negative conversion time of nucleic acid of 2019 novel coronavirus (2019-nCoV) by pharyngeal swab.Results:The baseline parameters of 4 groups before treatment was comparable. The negative conversion time of viral nucleic acid was (10.20±3.49), (10.11±4.68), (10.86±4.74), (8.44±3.51) days in LPV/r group, arbidol group, combination group, and supportive care group respectively ( F=2.556, P=0.058). There was also no significant difference in negative conversion rate of 2019-nCoV nucleic acid, the improvement of clinical symptoms, and the improvement of pulmonary infections by CT scan ( P>0.05). However, a statistically significant difference was found in the changing rates from mild/moderate to severe/critical type at day 7 (χ 2=9.311, P=0.017), which were 24%(6/25) in combination group, 16.7%(6/36) in arbidol group, 5.4%(3/56) in LPV/r group and 5.2%(3/58) in supportive care group. Moreover, the incidence of adverse reactions in three antiviral groups was significantly higher than that in supportive care group (χ 2=14.875, P=0.002). Conclusions:Antiviral treatment including LPV/r or arbidol or combination does not shorten the negative conversion time of 2019-nCoV nucleic acid nor improve clinical symptoms. Moreover, these antiviral drugs cause more adverse reactions which should be paid careful attention during the treatment.

Changes of total HIV-1 DNA in peripheral blood mononuclear cells of HIV-1/HCV co-infected patients after HAART / 中华临床感染病杂志

Objective:To analyze the dynamic changes of total HIV-1 DNA in peripheral blood mononuclear cells (PBMC) following highly active antiretroviral therapy (HAART) in HIV-1/HCV co-infected patients.Methods:Thirty patients with HIV-1/HCV co-infection without anti-HCV treatment (co-infected group) and 42 HIV-1 infected patients with initial treatment (mono-infected group) admitted to Guangzhou Eighth People’s Hospital from May 2015 to December 2017 were retrospectively analyzed. The virological and immunological responses of the two groups at 12, 24, 48, 72 and 96 weeks after HAART, the changes of total HIV-1 DNA in PBMC and its relationship with peripheral blood HIV-1 RNA and T lymphocyte subsets were observed. SPSS 22.0 statistical software was used to analyze the data.Results:The plasma HIV-1 virus inhibition rate, CD4 + T cells and CD4 + /CD8 + ratio increased and the total HIV-1 DNA in PBMC decreased in both groups after HAART. The inhibition rate of HIV RNA at week 72 in co-infected group was significantly lower than that in the mono-infected group ( χ2=7.93, P<0.01). Compared with the mono-infected group, the CD4 + T cells at week 12, 24, 72 and 96 after HAART were lower in the co-infected group ( U=313.50, 329.00, 286.00 and 204.50, P<0.05 or <0.01). The CD4 + /CD8 + ratio at week 48 in the co-infected group was lower than that in the mono-infected group ( U=294.50, P<0.05). The total HIV-1 DNA of the co-infected group at baseline and week 12 was lower than that of the mono-infected group ( U=362.00 and 359.00, P<0.01 or <0.05). There was no significant correlation between total HIV-1 DNA in PBMC and HIV-1 RNA or CD4 + /CD8 + ratio in both groups ( P>0.05). There was no correlation between total HIV-1 DNA and CD4 + T cells in HIV-1/HCV co-infected group ( b=-0.001, P>0.05), but it had negative correlation in the mono-infected group ( b=-0.001, P<0.05). Conclusion:Total HIV-1 DNA in PBMC was significantly decreased after HAART in HIV-1/HCV co-infected patients. Co-infected with HCV may delay the decrease of total HIV-1 DNA after HAART in patients with HIV-1 infection.

Clinical and pathological features of intestinal Talaromycosis marneffei infection in patients with acquired immunodeficiency syndrome / 中华传染病杂志

Objective:To investigate the clinical and pathological characteristics of acquired immunodeficiency syndrome (AIDS) patients with intestinal Talaromycosis marneffei (TM) infection. Methods:A total of 64 AIDS patients who underwent colonoscopy in Guangzhou Eighth People′s Hospital from January, 2010 to December, 2018 were retrospectively collected. Among them, 32 patients were co-infected with TM (AIDS with intestinal TM infection group) and 32 patients were not (AIDS without intestinal TM infection group) according to the colonic mucosa pathology. The clinical manifestations and pathological differences were compared between the two groups. Nonparametric rank sum test and Fisher exact probability method were used for statistical analysis.Results:The proportions of patients presented with fever, cough, retroperitoneal lymph nodes tume faction, nausea and vomiting, abdominal muscle tension, abdominal tenderness and rebound pain in AIDS with intestinal TM infection group were 28 (87.5%), 16 (50.0%), 13 (40.6%), 9 (28.1%), 8 (25.0%), 20 (62.5%) and 12 (37.5%), respectively, which were all significantly higher than those in AIDS without intestinal TM infection group 11 (34.4%), 6 (18.8%), 3 (9.4%), 2 (6.2%), 1 (3.1%), 8 (25.0%) and 1 (3.1%), respectively, the differences were statistically significant (Fisher exact test, all P<0.05). The median counts of peripheral blood CD4 + T lymphocyte, lymphocytes, monocytes, hemoglobin, platelet and albumin in AIDS with intestinal TM infection group were 13.5/μL, 0.30×10 9/L, 0.16×10 9/L, 88 g/L, 122×10 9/L and 23.5 g/L, respectively, which were all significantly lower than those in AIDS without intestinal TM infection group 207.0/ μL, 1.35×10 9/L, 0.35×10 9/L, 128 g/L, 201×10 9/L and 37.5 g/L, respectively, the differences were all statistically significant ( Z=-6.111, -6.191, -4.273, -5.353, -2.974 and-6.666, respectively, all P<0.05). Multivariate logistic regression analysis showed that CD4 + T lymphocytes <50/μL, hemoglobin <90 g/L and fecal occult blood positive were independent risk factors for AIDS with intestinal TM infection. The main manifestations of colonoscopy in AIDS with intestinal TM infection group were discontinuous ulcers (31.2%(10/32)), erosion (31.2%(10/32)) or co-exitance of ulcer and erosion (21.9%(7/32)), while suspected tumor-like eminence lesions were less common (15.6%(5/32)). The pathological features of colon mucosa were ulcer and/or erosion (53.1%(17/32)), chronic inflammation (46.9%(15/32)) and inflammatory granuloma (43.8%(14/32)). Oval or round spore with apparent septum could be seen by special staining. In AIDS with intestinal TM infection group, 27 patients were cured or improved, five patients died or deteriorated, while all patients in the AIDS without intestinal TM infection group improved after treatment without death. Conclusions:There are no specific gastrointestinal symptoms in AIDS patients with intestinal TM infection, while the patients present with decreased immunological cells and multiple colony pathological features. Specific fungal spores can be seen.

Clinical characteristics of forty-four cases of acute HIV-1 infection / 中华实验和临床病毒学杂志

Objective@#To investigate the clinical, immunological and virological characteristics of HIV-1 infected patients in the acute phase, for the sake of improving the diagnosis of acute infection with HIV-1.@*Methods@#We retrospectively analyzed the clinical manifestation and laboratory data of patients with acute HIV-1 infection who were admitted to the Center of Infectious Diseases, Guangzhou Eighth People’s Hospital from January 2012 to June 2017.@*Results@#Forty-four patients were enrolled into the study, 86.4% of them were male. 59.1% patients were homosexually transmitted. Clinical symptoms and signs mostly consisted of fever (84.1%), lymphadenopathy (56.8%) and so on, while 15.9% patients had central nervous system symptoms. Most common opportunistic infection included lung infection (50.0%) and oropharyngeal candidiasis (22.7%). Leucopenia (10 patients, 22.7%), and decreased CD4+ T cell count (267.5 cells/μl), inverted CD4+ /CD8+ ratio (86.4%) was mostly seen. Compared to patients who had HIV RNA load less than 6 lg copies/ml, the group of patients who had HIV RNA load more than 6 lg copies/ml had lower levels of CD4+ T cells (t=-3.724, P=0.001).@*Conclusions@#Patients with acute HIV infection have many different kinds of clinical symptoms and can be accompanied by opportunistic infection, and with high viremia.

Analysis on variation characteristics of HIV-1 Gp120 sequences in men who have sex with men in Guangzhou / 中华实验和临床病毒学杂志

Objective@#To analyze the variation characteristics of HIV-1 Gp120 sequences in men who have sex with men (MSM) in Guangzhou.@*Methods@#Plasma samples were collected from HIV-1 infected MSM before antiretroviral treatment. Viral RNA was extracted from plasma. Gp120 gene sequences were amplified by reverse transcription and nested-PCR using specific primers. Phylogenetic tree, length polymorphism, amino acid characteristics of V3 loop, co-receptors and signature amino acids were analyzed.@*Results@#The phylogenetic tree were divided into 4 clusters, and the most prevalent subtypes were CRF07_BC (34/61, 55.74%) and CRF01_AE (24/61, 39.34%). Majority of HIV-1 Gp120 sequences had 496-515 amino acids. Among five hypervariable regions, the V1 region had the highest levels of length polymorphism and V3 region had the lowest. The top four peptide of V3 loop were GPGQ (56/58, 96.55%). Most of the co-receptors HIV-1 strains used was CCR5(50/58, 86.21%)according to four methods of comprehensive prediction. There are four signature amino acids in CRF01_AE subtype strains, and the frequency of occurrence was 0.75-0.83; there are eight signature amino acids in CRF07_BC subtype strains, and the frequency was 0.74-0.94.@*Conclusions@#The length of Gp120 sequences in MSM in Guangzhou has a high polymorphism. The top four peptide of V3 loop, co-receptor and signature amino acid of V3 ring have formed unique patterns.

Analysis of antigen phenotypic epitopes variation in HBV Pre-S/S region in HIV/HBV co-infected patients / 中华实验和临床病毒学杂志

Objective@#To analyze the characteristic mutations of epitopes in HBV Pre-S/S region in HIV/HBV co-infected patients’ peripheral blood to provide basic data for studying the pathogenesis of HIV/HBV co-infection.@*Methods@#The chronic hepatitis B infected patients admitted to the Infectious Disease Center of the Eighth People′s Hospital of Guangzhou from January 2009 to December 2011 were enrolled into HIV/HBV co-infected group and HBV mono-infected group according to the result of HIV antibody detection respectively before treatment. HBV DNA in serum was extracted and Pre-S/S region of HBV DNA was amplified by nested-PCR. After sequencing of the obtained PCR products (direct sequencing), ContigExpress software was used for sequence splicing and BioEdit software was used for sequence alignment. With reference to the standard sequence of the matched genotype HBV, mutants of HBV Pre-S/S region in HIV/HBV co-infected group and HBV mono-infected group were analyzed respectively. Statistical analysis was performed by chi-square test with SPSS19.0 statistical analysis software.@*Results@#HBV Pre-S/S fragments were successfully amplified from 150 patients, including 90 cases of HIV/HBV co-infected group and 60 cases of HBV mono-infected group, with matched gender, age, genotype, HBeAg status, alanine aminotransferase (ALT), aspartate aminotransferase (AST). The result of analyzing mutants of HBV Pre-S/S region indicated that the incidence of mutation in all epitopes for cytotoxic T cells (CTL cells) was higher in the HIV/HBV co-infected group, and Pre-S2 aa1-15 epitope was significantly higher (χ2=6.964, P=0.008). The incidence of deletions in PreS2 aa1-15 epitope in HIV/HBV co-infected group (11.1%) was higher than HBV mono-infected group (3.3%) (χ2=2.959, P=0.085). In the B cell epitopes, the incidence of mutations in Pre-S2 aa1-26 in the HIV/HBV co-infected group was significantly higher than HBV mono-infected group (χ2=6.924, P=0.010), and there was no statistical significance between two groups in other B cell epitopes. No differences in helper T cell (Th cell) epitopes were found between the two groups.@*Conclusions@#Co-infection with HIV increased the CTL cell epitopes’ mutations in the HBV Pre-S/S region, especially the 5′ end epitope mutations in Pre-S2 region, which indicated that HBV mutation is related to the host immune status, and showed guiding information for further study on the pathogenesis of HIV/HBV co-infection

Preparation of Adriamycin Hydrochloride Magnetic Thermosensitive Liposome Based on TiO 2@Fe3O4 and Its Physicochemical Properties，Magnetic Effect and Photothermal Effect Study / 中国药房

OBJECTIVE： To prepare Adriamycin hydrochloride （DOX） magnetic thermosensitive liposome （MTSL）， investigate its physicochemical properties， magnetic effect and photothermal effect， so as to provide reference for tumor chemo- therapy and photodynamic/photothermal therapy. METHODS： Using DOX as model drug， TiO2@Fe3O4 as photosensitizers and magnetic materials， DOX-TiO2@Fe3O4-MTSL was prepared with membrane dispersion method. The morphology and dispersibility were observed； particle size and Zeta potential were detected； encapsulation efficiency of the liposome were determined by centrifugal ultrafiltration and HPLC. Its paramagnetism property was also detected by magnetometer. Compared with DOX solution， in vitro release behavior of the liposome was investigated by dialysis method， and the release curves at different temperatures （at 37， 43 ℃） were compared. The photothermal conversion effect of the liposome and the production of reactive oxygen species （ROS） in human breast cancer MCF-7 cells were investigated by near infrared laser irradiation at 808 nm. RESULTS： Prepared DOX-TiO2@Fe3O4-MTSL was brown-black with good water dispersion， and was spherical in shape and uniform in size under electron microscopy. Average particle size was 250.6 nm； polydispersity index was 0.107； Zeta potential was （－7.76±3.41）mV； encapsulation efficiency was （92.3±3.2）％. Under the external magnetic field， the liposome could move in a directional direction and had obvious paramagnetism. Compared with DOX solution， the liposomes released slowly and showed obvious sustained- release characteristics. Compared with at 37 ℃， the drug release of liposome speeded up significantly at 43 ℃.With the increase of laser （808 nm） irradiation time， the temperature of the liposome kept rising， which had obvious photothermal conversion effect and could induce the increase of ROS in MCF-7 cells. CONCLUSIONS： DOX-TiO2@Fe3O4-MTSL is prepared succe- ssfully， which has uniform appearance， good physical and chemical properties. It has obvious paramagnetism sustained release effect and photothermal conversion efficiency， and can promote ROS production in MCF-7 cells under near infrared laser irradiation at 808 nm.

Optimization of Preparation Technology of Near-infrared Light Response-based Doxorubicin Hydrochloride Nano-liposomes / 中国药房

OBJECTIVE： To establish a methaod for content determination of doxorubicin hydrochloride nano-liposomes， and to optimize its preparation technology. METHODS： The contents of doxorubicin hydrochloride nano-liposomes was determined by UV spectrophotometry. The membrane dispersion method was used to prepare doxorubicin hydrochloride nano-liposomes. Using particle size， encapsulation efficiency and drug-loading amount as indexes， the weight ratio of phospholipid to drug （mg/mg）， the weight ratio of phospholipid to cholesterol （mg/mg） and ultrasonic time （min） as factors， central composite design-response surface methodology was used to optimize the preparation technology. The photothermal conversion effect of doxorubicin hydrochloride nano-liposomes was investigated by near infrared irradiation. RESULTS： The linear range of doxorubicin hydrochloride were 1.01-16.16 μg/mL（r＝0.999 7）； precision， stability and reproducibility tests were all in line with the requirments of Chinese Pharmacopoeia. The optimal preparation technology included that the weight ratio of phospholipid to drug was 13.30 ∶ 1（mg/mg）； the weight ratio of phospholipid to cholesterol was 4.09 ∶ 1 （mg/mg）； the ultrasonic time was 10 min. Under this technology， the particle size and drug-loading amount of doxorubicin hydrochloride nano-liposomes were （200.5±25.1） nm and （11.02±0.20）％， relative errors of which to predicted value （196.3 nm， 10.68％） were 1.82％ and 1.63％. The consistency between measured value and predicted value was good. Doxorubicin hydrochloride nano-liposomes exhibited concentration- dependent and time-dependent photothermal conversion characteristics under near infrared irradiation at 808 nm. CONCLUSIONS： Established method is simple and good accuracy. The optimized preparation technology is simple and feasible.

Characterization and primary resistance mutations in gag-pol gene of human immunodeficiency virus-1 CRF07_BC strain in Guangdong Province / 中华传染病杂志

Objective To investigate the genetic variations of gag-pol gene in human immunodeficiency virus-1(HIV-1) CRF07_BC strain in Guangdong Province.Methods From February to September in 2015,plasma samples of 78 cases with HIV 1 CRF07_BC infection in Guangdong were collected before antiretroviral treatment.Viral RNA was extracted from plasma.Gene (gag and pol) sequences were amplified by reverse transcriptase and nested-PCR using specific primers.Phylogenetic tree,genic dispersion rate,nucleotide polymorphism,selection pressure and variation characteristics were analyzed.Results The main transmission route of the enrolled patients was homosexual transmission (80.77％,63/78).The gag pol gene phylogenetic tree was divided into two sub-clusters.The strains from different transmission routes were not in cluster.The average genetic dispersion rate and average entropy of gag gene were both higher than those of pol gene.The average genetic dispersion and average entropy of p17 and p6 regions of gag gene were both higher than those of p24.The average genetic dispersion and average entropy of pol gene were higher than those of rt region.The average ds/dn values of gag and pol genes were greater than one.Compared with the common HIV-related antigenic epitopes (A2,A11,B39,B60,Cw1,Cw3,Cw8),the cytotoxic lymphocyte (CTL) epitope mutations in the P17 region were more in the consensus of GAG region than those in the P24 region.The epitope conserved rates were 26.92％,0,1.28％,0,96.15％,82.05％,84.62％ and 98.72％,respectively.The drug resistance rate of pol gene was 2.56％ (2/78).Conclusions The gag and pol genes of CRF07_BC strain in Guangdong are all mutated.Diversity of gag gene is greater than that of pol gene,and gag gene variation is mainly in p17 and p6 regions.gag and pol genes are both affected by negative selection pressure.P17 protein CTL epitope variability is greater than P24 protein epitope.The prevalence of drug resistance mutation is lower than the threshold.It's important to monitor the spread of drug-resistant strains.

Research on the causes of death associated with combined effects of HBV and HCV infection in patients with acquired immunodeficiency syndrome / 中华肝脏病杂志

Objective@#To investigate the combined effects of hepatitis B virus and hepatitis C virus (HBV/HCV) infection on the cause of death in patients with acquired immunodeficiency syndrome (AIDS).@*Methods@#The causes of death of 111 cases of AIDS with HBV/HCV (combined infection group) and 210 AIDS patients (single infection group) admitted to our hospital from 2012 to 2016 data were compared using chi-square test.@*Results@#There was no statistically significant difference in gender composition and age in the combined infection groups (P > 0.05). The main causes of death in the combined infection group were severe pneumonia (44.1%), end-stage liver disease (18.9%), and central nervous system infection (14.4%). The main causes of death in the single infection group were severe pneumonia (47.6%) and central nervous system infection (14.3%) and tumor (13.3%). There was no case of end-stage liver disease. The ratio of end-stage liver disease in the former group was significantly higher than that in the latter group (χ2 = 42.511, P < 0.001). The main cause of death in 12 HIV/HBV/HCV triple-infected patients was end-stage liver disease, accounting for 41.7%, which was significantly higher than 18.9% of end-stage liver disease in HIV/HBV or HIV/HCV dual infection (99 cases). And the difference was statistically significant (χ2 = 4.539, P = 0.033); however, the ratio of end-stage liver disease in 50 HIV/HBV co-infected patients and 49 HIV/HCV co-infected patients was 16.0% vs. 16.3%, respectively, and the difference was not statistically significant (χ2 = 0.002, P = 0.965). In the co-infected group, 36 patients had CD4+ cell counts >100/μl, the primary cause of death was end-stage liver disease, accounting for 38.2%. 75 patients with CD4+ ≤ 100/μl died due to end-stage liver disease, accounting for 9.3% and the difference was statistically significant (χ2 = 13.852, P < 0.05).@*Conclusion@#End-stage liver disease is the main cause of death in patients with AIDS combined with HBV or HCV, especially triplet infection and CD4+ cell count > 100/μl. An early diagnosis and treatment of HBV or HCV infection should commence as soon as possible.

Discussion on optimal duration of pegylated interferon α combined with ribavirin for chronic hepatitis C in HIV-infected patients / 中华肝脏病杂志

Objective@#To investigate the optimal duration of pegylated-alpha interferon (Peg-INFα) combined with ribavirin (RBV) in treating chronic hepatitis C infection in human immunodeficiency virus (HIV)-infected patients.@*Methods@#A multicenter prospective study was conducted. The study subjects were divided into two groups; HIV/HCV co-infections (Group A, n = 158) and control with HCV-monoinfections (Group B, n = 60). All recruited patients received standard Peg-INFα plus RBV therapy. Group A was divided into 3 subgroups according to CD4+ cell counts: A1 subgroup, 79 cases, CD4+ counts > 350 cells /μl, who received anti-HCV before combination antiretroviral therapy(cART); A2 subgroup, 45 cases, CD4+ counts between 200 and 350 cells/μl, who did not start anti-HCV until they could tolerate cART well; A3 subgroup, 34 cases, CD4+ counts < 200 cells /μl, cART was administered first, and anti-HCV therapy was started when CD4+ counts > 200 cells/μl. The anti-HCV efficacy of two groups and 3 subgroups were compared. Statistical analysis for normal distribution and homogeneity of variance data was calculated by t-test and the counting data was analyzed by χ 2 test. The Mann-Whitney U test was used for non-normal data. A one-way analysis of variance (ANOVA) was used for the comparison of multiple groups, followed by SNK method. Multiple independent samples were used for non-parametric tests.@*Results@#There was no significant difference in age and baseline HCV RNA levels between groups and subgroups (P > 0.05). By an intent-to-treat (ITT) analysis, in Group A, the ratio of complete early virological response (cEVR) rate was 75.3% (119/158), the ratio of end of treatment virological response (eTVR) rate was 68.4% (108/158), and the ratio of sustained virological response (SVR) rate was 48.7% (77/158); in Group B, the ratio of cEVR rate was 93.3% (56/60), the ratio of eTVR rate was 90.0% (54/60), and the ratio of SVR rate was 71.7% (43/60); The therapeutic index of Group A were lower than those of Group B (P≤0.05). By per-protocol (PP) analysis, the ratio of cEVR rate in Group A [75.2% (88/112)] was still lower than that in Group B [93.3% (56/60)], but no significant differences were found in the ratio of eTVR rate and SVR rate between 2 groups (P > 0.05). Comparing the efficacy of subgroups (A1, A2 and A3) by ITT analysis, the ratios of cEVR rate were respectively 78.5% (62/79), 75.6% (34/45) and 67.6% (23/34); the ratios of eTVR rate were respectively 68.4%(54/79), 80.0%(36/45)and 52.9%(18/34); and the ratios of SVR rate were respectively 41.8%(33/79), 64.4%(29/45)and 44.1%(15/34). The ratio of eTVR in subgroup A2 was obviously higher than that in subgroup A3 and the ratio of SVR in subgroup A2 was statistically higher than that of subgroup A1(P≤0.05). However, by PP analysis, no significant differences of the therapeutic indexes were found among the respective subgroups (P > 0.05).@*Conclusion@#HIV-HCV co-infected patients would have better anti-HCV efficacy with Peg-INFα-2a plus RBV than HCV- monoinfected patients. The best time for initiating anti-HCV therapy in HIV-HCV co-infected patients is when CD4+ counts 200 cells/ μl.

Pathogenic spectrum, clinical features and drug resistance of pneumonia caused by nontuberculous mycobacteria in acquined immunodeficiency syndrome patients / 中华传染病杂志

Objective To explore the pathogen spectrum, drug resistance rate and clinical characteristics of pneumonia caused by non-tuberculous mycobacteria (NTM) in acquined immuno-deficiency syndrome (AIDS) patients.Methods The clinical data of 31 hospitalized AIDS patients with bronchoalceolar lavage flind (BALF) culture confirmed NTM pulmonary disease in Guangzhou No.8 People′s Hospital from January,2008 to February,2015 were retrospectively analyzed, including pathogen spectrum, drug resistance rate and clinical characteristics.The clinical characteristics and drug resistance were compared between Mycobacterium avmm-intracellulare complex (MAC) pneumonia and the non-MAC pneumonia, and t test and chi-square test were used.Results Of the 31 AIDS patients,28 were male and 3 were female, with the mean age of 40.9 years old.The 31 NTM strains were consisted of 14 MAC strains and 17 non-MAC strains (including 4 M.kansasii strains,3 M.lentiflavumstrains, 2 M.szulgai strains, 2 M.yongonense strains etc).There was no significant difference between two groups in sex ratio, mean age, clinical manifestations, laboratory tests and treatment outcome (all P>0.05).The major clinical manifestations included fever, productive cough, weight loss, anemia and low CD4+ count (<50/μL).Most patients showed thoracic lymphadenectasis and patchy shadows in lungs, and few patients had millet shadows and pericardial effusion.Compared with non-MAC strains, MAC strains had higher drug resistant rate of moxifloxacin (10/14 vs 4/17), levofloxacin (14/14 vs 8/17), and clarithromycin (11/14 vs 7/17).More extensively drug resistance strains were seen in non-MAC strains compared with MAC strains (11/14 vs 7/17).Conclusions MAC is the most common pathogen of NTM pulmonary disease in AIDS patients.The clinical features of pneumonia caused by MAC and non-MAC are similar, but drug resistance of MAC strains are more severe.

Diagnostic value of serum Mp1p antigen detection for Talaromyces marneffei infection in acquired immune deficiency syndrome patients / 中华传染病杂志

Objective To explore the diagnostic value of Talaromyces marneffei (T.marneffei)-specific mannose glycoprotein Mp1p antigen for T.marneffei infection in acquired immune deficiency syndrome (AIDS) patients.Methods All cases were recruited in this study from January 2012 to June 2015 in Guangzhou No.8 People′s Hospital, including 184 AIDS patients with T.marneffei infection confirmatively diagnosed by culture, and 205 controls including 176 AIDS patients without T.marneffei infection and 29 health controls.Double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were both utilized to detect serum Mp1p antigen levels, and their sensitivity and specificity for diagnosing T.marneffei infection in patients with AIDS were analyzed.x2 test and t test were used for statistical analysis.Results The ratio of males to females and age of the study group were both comparable to those of the control group (x2=0.019, P=0.889;t=1.810,P=0.07, respecitvley).The sensitivities of double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were 82.07%(151/184) and 83.15%(153/184), respectively (x2=0.076, P=0.783).The specificities were 93.17%(191/205) and 92.68%(190/205), respectively (x2=0.037, P=0.847).The accuracy values were 87.92%(342/389) and 88.17%(343/389), respectively (x2=0.012, P=0.912).The false positive rates were 6.83%(14/205) and 7.32%(15/205), respectively.The false negative rates were 17.93%(33/184) and 16.85%(31/184), respectively (x2=0.049, P=0.829).The positive predictive values were 91.52%(151/165) and 91.07%(153/168), respectively (x2=0.021, P=0.886).The negative predictive values were 85.27%(191/224) and 85.97%(190/221), respectively (x2=0.045, P=0.832).The Kappa values were 0.83 and 0.80, respectively.Conclusion Detection of serum Mp1p antigen of T.marneffei possesses high specificity and sensitivity, which may be utilized for rapid and early diagnosis of T.marneffei infection in patients with AIDS.