Kinetic Characteristics of Neutralizing Antibody Responses Vary among Patients with COVID-19 / 生物医学与环境科学（英文）

Objective@#The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).@*Methods@#In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2.@*Results@#NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective.@*Conclusion@#We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.

Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study / 中华医学杂志(英文版)

BACKGROUND@#Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.@*METHODS@#We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.@*RESULTS@#At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.@*CONCLUSIONS@#The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.@*TRIAL REGISTRATION@#ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

Comparison of antibiotic resistance spectrum between methicillin-resistant and methicillin-susceptible coagulase-negative staphylococci nasal isolates among 1 001 HIV infectors / 中华疾病控制杂志

Objective We aimed to elucidate the prevalence and the antibiotic resistance spectrum of nasal coagulase-negative staphylococci (CoNS) colonization among HIV infectors in Guangzhou. Method After isolation and identification, all CoNS isolates were tested for the antibiotic susceptibility, and the antibiotic resistance genes. Result Among the 1 001 HIV infectors, the prevalence of CoNS and MRCoNS were 57.44% and 48.15%, respectively. The three predominant resistant antibiotics of MRCoNS isolates were penicillin, erythromycin and trimethoprim-sulfame thoxazole, while predominant detection rates of genes were Aac(6’)-aph(2’)、ermC and linA genes. The multidrug resistance rate of MRCoNS isolates were significantly higher than methicillin-susceptible coagulase-negative staphylococci (MSCoNS) isolates (80.69% versus 39.66%, P<0.001, OR=6.36). Conclusions The prevalence and multidrug resistant rates of nasal colonization CoNS and MRCoNS are high among HIV infectors in Guangzhou. MRCoNS isolates were 6.36 times more likely to be of multidrug resistance than MSCoNS isolates.

Efficacy and Safety of Tenofovir and Lamivudine in Combination with Efavirenz in Patients Co-infected with Human Immunodeficiency Virus and Hepatitis B Virus in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China. Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV.</p><p><b>METHODS</b>One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen of TDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed.</p><p><b>RESULTS</b>Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%). Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min-1·1.73 m-2) to week 12 (104 ml·min-1·1.73 m-2) but was almost back to baseline at week 48 (111 ml·min-1·1.73 m-2).</p><p><b>CONCLUSION</b>This combination ART regimen is safe and effective for patients with HIV/HBV co-infection.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555.</p>

Analysis of death causes of 345 cases with HIV/AIDS in Guangdong area / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To analyze the death causes of 345 cases with HIV/AIDS in Guangdong area.</p><p><b>METHODS</b>The situations of 345 hospitalized death cases with HIV/AIDS were conducted by retrospective analysis.</p><p><b>RESULTS</b>(1)There were total 3406 hospitalized cases with HIV/AIDS in a hospital from January 2001 to December 2011 and 345 cases died, the fatality rate was 10. 13%. Since 2005 the introduction of free anti-viral treatment, the fatality rate of HIV/AIDS declined. The fatality rate of the patients whose CD4+ T lymphocyte counts <200 cells/microl was 14.61% (299/2046) and it was significantly higher than that of patients whose CD4 T lymphocyte counts >or=200 cells/microl (P <0.01). (2) 99.42% of the death cases had more than one kind of opportunistic infections (OI) and there were 924 cases of OI totally. 84. 64% of OI related to the death directly. Fungal infection was the most common in OI, followed by bacterial infection. Most OI occurred in the lungs, mouth, other systemic disseminated diseases, gastrointestine, central nerver system, septicemia, skin. The AIDS defining opportunistic infections such as several pneumonia, disseminated penicilliosis marneffei and CNS infections accounted for 29.65%. Other factors that caused HIV/AIDS death included opportunistic tumors, HIV related disease and non AIDS-related disease accounted for 15.36%. No accepted effective highly active antiretroviral therapy (HARRT) also constituted factors of death. Among cases which accepted HARRT treatment, only 6.96% had the period of treatment over three months.</p><p><b>CONCLUSION</b>The fatality rate of end-stage AIDS patients was high and the opportunistic infections was the most important cause of death. Early diagnosis and treatment for opportunistic infections, timely effective HARRT were the key to improve the quality of life of AIDS patients.</p>

Differential response to pegylated interferon plus ribavirin combination therapy in chronic hepatitis C and HIV/HCV co-infected patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the potential differences in response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) combination therapy in patients with hepatitis C virus (HCV) mono-infection and human immunodeficiency virus (HIV)/HCV co-infection.</p><p><b>METHODS</b>Seventy HIV/HCV patients and sixty HCV patients, were administered a 48-week course of Peg-IFN + RBV. The HCV load was tested by the COBAS automatic viral load analysis system (lower limit of quantification = 15 IU/ml) at treatment weeks 0 (baseline), 4, 12, 24, and 48 and at week 24 after drug withdrawal. The patients were also genotyped by sequencing for the host-encoded interleukin (IL)-28B single nucleotide polymorphisms (SNPs) related to HCV Peg-IFN + RBV therapy outcome: rs8099917, rs12979860 and rs12980275. In addition, the HCV-encoded NS5B gene region was genotyped by nested-PCR and sequencing followed by BLAST searching of the Los Alamos National Laboratory HCV database. The significance of between-group differences in response to therapy and roles of SNPs were evaluated by statistical analyses.</p><p><b>RESULTS</b>The ratio of sustained virological response (SVR) was significantly lower in the HIV/HCV co-infected patients than the HCV mono-infected patients (32.9% vs. 71.7%; P less than 0.001). While the HIV/HCV co-infected patients did not show a significant difference in SVR ratio achieved between individuals infected with the HCV-1 genotype and the non-HCV-1 genotype (30.8% vs. 33.3%; P = 1.000), the HCV mono-infected patients did (86.1% vs. non 50.0%, P = 0.002). Moreover, the SVR ratio was higher in the HCV-1 genotype HCV mono-infected patients than in the HIV/HCV-1 genotype co-infected patents (30.8% vs. 86.1%; P less than 0.001). The different IL-28B genotypes were not significantly correlated to the PEG-IFN+RBV therapy response of either HCV mono-infected patients or HIV/HCV co-infected patients (P more than 0.05).</p><p><b>CONCLUSION</b>HCV mono-infected patients respond better to Peg-IFN + RBV therapy than HIV/HCV co-infected patients. The HCV-1 genotype may promote this therapy response in HCV mono-infected patients, but the IL-28B genotypes appear to play no significant role.</p>

Genetic diversity analysis of Penicillium marneffei isolated from AIDS patients in Guangdong, China using randomly amplified polymorphic DNA / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Penicillium marneffei (P. marneffei) is an emerging pathogenic fungus that can cause invasive mycosis in patients with AIDS. The epidemiological features of P. marneffei infection in AIDS patients in Guangdong province remain unclear so far. This study aimed to investigate the genetic diversity within a population of 163 P. marneffei isolates obtained from AIDS patients and search for the dominant clinical strains in Guangdong province.</p><p><b>METHODS</b>One hundred and sixty-three P. marneffei isolates obtained from AIDS patients in Guangdong province during January 2004 and December 2009 were studied by randomly amplified polymorphic DNA (RAPD) using two random primers (H2 and H22). The degree of similarity between samples was calculated through similarity coefficients from RAPD fragment data and the dendrogram was assessed using the unweighted pair group method with arithmetic mean (UPGMA).</p><p><b>RESULTS</b>Two primers showed a high degree of discrimination and good stability. Primer H2 yielded eight different patterns (H2-1 to H2-8) among 163 isolates with the discriminatory power being 0.413. Primer H22 identified seven types (H22-1 to H22-7) among 163 isolates with the discriminatory power being 0.467. Genetic similarity coefficients based on RAPD data among 163 P. marneffei isolates ranged from 0.681 to 0.957, 61.96% of which were no less than 0.83. The discriminatory power of the two primers was 0.524. One hundred and sixty-three P. marneffei isolates were clustered into nine distinct groups (groups I to IX) at the similarity coefficient value of 0.83 and group I was the most common, including 101 strains (61.96%).</p><p><b>CONCLUSION</b>The RAPD analyses could provide important information as to the degree of genetic diversity and the relationship among clinical P. marneffei isolates, revealing genetic polymorphism and dominant strains.</p>

Analysis of hepatitis C virus (HCV) subtypes in HIV/HCV co-infected and HCV mono-infected individuals in Guangdong province / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the transmission routes, genotypes/subtypes distribution and genetic character of HCV in HIV/HCV co-infected and HCV mono-infected individuals in Guangdong Province.</p><p><b>METHODS</b>Reverse transcription (RT) nested PCR was performed to amplify the HCV NS5B gene region from 95 HIV/HCV co-infected and 99 HCV mono-infected individuals lived in Guangdong province. The PCR products were then sequenced for HCV subtyping. Genetic analysis was done by MEGA4 software.</p><p><b>RESULTS</b>(1) HIV/HCV co-infected individuals infected HCV mostly through injection drug use (IDU, 78.9%), the HCV subtypes were identified as 6a (53.7%), 3a (17.9%), 1b (15.8%), 3b (11.6%) and 1a (1.0%) respectively, the genetic distance within subtype 1b was longer than those within other subtypes, the predominant HCV subtype in HIV/HCV co-infected individuals infected through IDU was 6a (60.0%). (2) HCV mono-infected individuals infected HCV mostly through blood or blood products transfusions (80.8%), the HCV subtypes were identified as 1b (67.7%), 6a (17.2%), 3a (6.1%), 2a (5.0%), 3b (2.0%), 4a (1.0%) and 5a (1.0%) respectively, the genetic distance within subtype 1b was also longer than those within other subtypes, the predominant HCV subtype in HCV mono-infected individuals infected through blood or blood products transfusions was 1b (76.2%).</p><p><b>CONCLUSION</b>The diversity of HCV subtypes in HIV/HCV co-infected and HCV mono-infected individuals in Guangdong Province was high, both the major transmission route and HCV subtype between HIV/HCV co-infected individuals and HCV mono-infected individuals were different.</p>

Epidemiologic and therapeutic status study of patients with hepatitis C / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the different infective mode, the time from be infectived to be diagnosed and the time from be diagnosed to be treated of patients with hepatitis C.</p><p><b>METHODS</b>The different infective mode, the time from be infectived to be diagnosed and the time from be diagnosed to be treated of 216 patients with hepatitis C from march 2004 to march 2009 were retrospectively analyzed.</p><p><b>RESULTS</b>72.22 percents patients suffered from post transfusion hepatitis C (PTHC) and 27.78 percents patients suffered from sporadic hepatitisC (SHC). 32.61 percents patients were diagnosed after be infectived 15-20 years later. 3.26 percents patients were diagnosed after be infectived more than 20 years later. 33.80 percents patients were treated after be diagnosed more than 5 years later. 17.13 percents patients were treated after be diagnosed 10-15 years later.</p><p><b>CONCLUSION</b>Most patients were infectived with hepatitis C by transfusing blood or blood products. Most patients were diagnosed after be infectived more than 15 years later. Almost half of patients were treated after be diagnosed more than 5 years later, and a significant portion of percents patients were treated after be diagnosed more than 10 years later.</p>

Liver injury in HIV-1-infected patients receiving non-nucleosides reverse transcriptase inhibitors-based antiretroviral therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Liver injury is one of the most important adverse effects of antiretroviral therapy, leading to therapy changing or discontinuation. Data on liver injury in human immunodeficiency virus-1-infected patients receiving antiretroviral therapy are limited in China. The purpose of this study was to investigate the features of liver injury in human immunodeficiency virus type 1-infected patients receiving non-nucleosides reverse transcriptase inhibitors-based antiretroviral therapy in China.</p><p><b>METHODS</b>Seventy-five patients on antiretroviral therapy containing non-nucleosides reverse transcriptase inhibitors were retrospectively studied. The patients were divided into 2 groups: group 1 (with liver injury, n = 45) and group 2 (without liver injury, n = 30). The features of liver injury were analyzed. The sex, age, baseline CD4 counts, hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection, hepatotoxic drug use and nevirapine or efavirenz use were compared between two groups.</p><p><b>RESULTS</b>Forty-five patients (60.0%), 31 (68.9%) males and 14 (31.1%) females, aged 12 to 52 years (averaged (39 ± 9) years), experienced at least one episode of liver injury. Forty (53.3%) patients were co-infected with HBV and/or HCV, 42 (56%) patients had concomitant use of antituberculosis drugs or cotrimoxazole, 46 (61.3%) and 29 (38.7%) patients received regimen containing nevirapine and efavirenz, respectively. Grade 1 liver injuries were observed in 26 (57.8%) patients, grade 2 in 16 (35.6%), grade 3 in 2 (4.0%) and grade 4 in 1 (2.2%). Three (6.7%) patients discontinued highly active antiretroviral therapy (HAART) due to liver injury. In group 1, there were 29 (64.4%) patients co-infected with HBV and/or HCV, 32 (71.1%) patients received regimen containing nevirapine, and 30 (66.7%) patients had concomitant use of anti-tuberculosis drugs or cotrimoxazole, respectively, significantly higher than those in group 2 (11 (36.7%), 14 (46.7%) and 12 (40%), respectively; P = 0.018, 0.033, 0.023, respectively). The sex, age, baseline CD4 counts and disease stage were not factors associated with liver injury.</p><p><b>CONCLUSIONS</b>Liver injury associated with HAART containing non-nucleosides reverse transcriptase inhibitors was mild to moderate and those who were co-infected with HBV and/or HCV, had concomitant use of antituberculosis drugs or cotrimoxazole and received a regimen containing nevirapine were prone to liver injury while receiving HAART.</p>

Detection of cryptosporidium infection among AIDS patients in Guangdong and Yunnan / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the infection of Cryptosporidium and its epidemiological characteristics in AIDS patients of Southern China.</p><p><b>METHODS</b>Stool samples colleted from AIDS confirmed patients. The samples were detected for oocyst of Cryptosporidium by acid fast bacteria stain and indirect fluorescent antibody stain respectively, CD4 count was detected by Flow Cytometry.</p><p><b>RESULTS</b>212 samples of fresh stool obtained from the AIDS patients who live in Guangdong and Yunnan province. The total infection rate of Cryptosporidium in AIDS patients was 4.25% (9/212), the infectious rate of oocyst in the group of 50- 59-years-old was significantly higher than those in 30-39 (P < 0.01); the infectious rate of oocyst in patients with antiretroviral therapy (ART) was also significantly lower (P = 0.0000); we found the patients coinfected with Cryptosporidium with CD4 count all below 100 cells/microl. However, there were no any difference between the infectious rate to the patient's gender, areas and stool shape.</p><p><b>CONCLUSION</b>AIDS patients infected by Cryptosporidium are not rare in southern China, and the infectious rate was lower than western country. Patients received ART could decrease the infectious rate of Cryptosporidium, Cryptosporidium always happen in patient whose CD4 count was very low (< 100 cells/microl).</p>

Clinical characteristics of the patients with dengue fever seen from 2002 to 2006 in Guangzhou / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of the patients with dengue fever (DF) seen from 2002 to 2006 in Guangzhou in order to prevent and treat dengue fever better.</p><p><b>METHODS</b>Clinical data from 1342 inpatients with DF seen from 2002 to 2006 were retrospectively analyzed. The dengue virus was isolated by C6/36 cell culture and genotyped by reverse transcriptase-polymerase chain reaction and gene sequence analysis.</p><p><b>RESULTS</b>The average age of the patients was 34.4 years, without sex difference in distribution. Most of the patients had obvious toxemic symptoms including fever (100 percent), headache (85.9 percent), myalgia (64.5 percent), bone soreness (46.6 percent) and skin rash (65.9 percent). Leukopenia, thrombocytopenia, elevated alanine aminotransferase, elevated aspartate aminotransferase and hypokalemia were found in 66.0 percent, 61.3 percent, 69.0 percent , 85.7 percent and 28.4 percent of patients, respectively. DF-IgM could be detected in 90 percent of patients. The virus was identified as dengue virus type-I.</p><p><b>CONCLUSIONS</b>The epidemic of DF was caused by dengue virus- I from 2002 to 2006 in Guangzhou. Most of the patients had classic DF clinical manifestation with high percentage of hepatic injury. Few patients progressed to dengue hemorrhagic fever.</p>