Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

OBJECTIVE: To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use. METHODS: Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r). RESULTS: The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results. CONCLUSIONS In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.
Databases, Pharmaceutical ; Decision Making, Computer-Assisted ; Drug Monitoring ; Drug-Related Side Effects and Adverse Reactions ; HIV Protease Inhibitors ; adverse effects ; pharmacology ; Humans ; Liver ; drug effects ; Lopinavir ; adverse effects ; toxicity ; Models, Statistical ; Reproducibility of Results ; Software ; standards

BACKGROUND: Recent findings in molecular pathology suggest that genetic translocation and/or overexpression of oncoproteins is important in salivary gland tumorigenesis and diagnosis. We investigated PLAG1, SOX10, and Myb protein expression in various salivary gland neoplasm tissues. METHODS: A total of 113 cases of surgically resected salivary gland neoplasms at the National Cancer Center from January 2007 to March 2017 were identified. Immunohistochemical staining of PLAG1, SOX10, and Myb in tissue samples was performed using tissue microarrays. RESULTS: Among the 113 cases, 82 (72.6%) were benign and 31 (27.4%) were malignant. PLAG1 showed nuclear staining and normal parotid gland was not stained. Among 48 cases of pleomorphic adenoma, 29 (60.4%) were positive for PLAG1. All other benign and malignant salivary gland neoplasms were PLAG1-negative. SOX10 showed nuclear staining. In normal salivary gland tissues SOX10 was expressed in cells of acinus and intercalated ducts. In benign tumors, SOX10 expression was observed in all pleomorphic adenoma (48/48), and basal cell adenoma (3/3), but not in other benign tumors. SOX10 positivity was observed in nine of 31 (29.0%) malignant tumors. Myb showed nuclear staining but was not detected in normal parotid glands. Four of 31 (12.9%) malignant tumors showed Myb positivity: three adenoid cystic carcinomas (AdCC) and one myoepithelial carcinoma with focal AdCC-like histology. CONCLUSIONS: PLAG1 expression is specific to pleomorphic adenoma. SOX10 expression is helpful to rule out excretory duct origin tumor, but its diagnostic value is relatively low. Myb is useful for diagnosing AdCC when histology is unclear in the surgical specimen.
Adenoma ; Adenoma, Pleomorphic ; Antibody-Dependent Cell Cytotoxicity ; Carcinogenesis ; Carcinoma, Adenoid Cystic ; Diagnosis ; Immunohistochemistry ; Oncogene Proteins ; Oncogene Proteins v-myb ; Parotid Gland ; Pathology, Molecular ; Salivary Gland Neoplasms ; Salivary Glands ; SOX Transcription Factors ; Translocation, Genetic

The diagnostic criteria for sequential rapidly destructive coxarthrosis remain unclear and this condition is rarely reported in patients with human immunodeficiency virus (HIV). Here, we report a case of an HIV-infected 73-year old female who experienced hip joint destruction. The patient was diagnosed with HIV in 2012 (at age 68 years) and began continuous treatment with nucleoside reverse transcriptase and protease inhibitors. Twenty-nine months after her HIV diagnosis, the patient experienced osteonecrosis of the right hip and underwent a total hip arthroplasty (THA). Twelve months post right-hip THA, X-ray results showed good outcomes. Eight months later (20 months post THA), however, osteolysis of the left femoral head was detected upon radiological exam and THA of the left hip was performed; chronic inflammation and fibrosis were identified in the resultant biopsy. Favorable results were obtained at 3 months after the second surgery.
Arthroplasty, Replacement, Hip ; Biopsy ; Diagnosis ; Female ; Femur Head ; Fibrosis ; Head ; Hip ; Hip Joint ; HIV ; Humans ; Humans ; Inflammation ; Osteoarthritis, Hip ; Osteolysis ; Osteonecrosis ; Protease Inhibitors ; RNA-Directed DNA Polymerase

Atazanavir is a protease inhibitor approved for use in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus infection. Atazanavir and other protease inhibitors can sometimes induce corrected QT prolongation and ventricular arrhythmia. A 40-year-old man with no comorbidities, except human immunodeficiency virus 1 infection, presented with palpitations 3 days after an overdose of 150 caps of atazanavir, with suicidal intent. His initial electrocardiogram showed monomorphic ventricular tachycardia, and hyperbilirubinemia was observed in his initial blood test. Immediately after magnesium sulfate infusion, his ventricular tachycardia was converted into junctional bradycardia with prolonged corrected QT. After 3 days of close observation in the intensive care unit, the corrected QT prolongation and hyperbilirubinemia were normalized.
Adult ; Arrhythmias, Cardiac ; Atazanavir Sulfate* ; Bradycardia ; Comorbidity ; Electrocardiography ; Hematologic Tests ; HIV ; HIV-1 ; Humans ; Hyperbilirubinemia ; Intensive Care Units ; Magnesium Sulfate ; Protease Inhibitors* ; Tachycardia, Ventricular*

Currently, metabolic complications are the most common problem among human immunodeficiency virus (HIV)-infected patients, with a high incidence. However, there have been very few studies regarding metabolic abnormalities published in Asia, especially in Korea. This cross-sectional study was performed to investigate the prevalence of and risk factors for metabolic abnormalities in 1,096 HIV-infected patients of the Korea HIV/AIDS cohort study enrolled from 19 hospitals between 2006 and 2013. Data at entry to cohort were analyzed. As a result, the median age of the 1,096 enrolled subjects was 46 years, and most patients were men (92.8%). The metabolic profiles of the patients were as follows: median weight was 63.8 kg, median body mass index (BMI) was 22.2 kg/m², and 16.4% of the patients had a BMI over 25 kg/m². A total of 5.5% of the patients had abdominal obesity (waist/hip ratio ≥ 1 in men, ≥ 0.85 in women). Increased levels of fasting glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were present in 10.4%, 6.0%, 5.5%, and 32.1% of the patients. Decreased high-density lipoprotein (HDL) cholesterol levels were observed in 44.2% of the patients. High systolic blood pressure was present in 14.3% of the patients. In multivariate analysis, high BMI and the use of protease inhibitors (PIs) were risk factors for dyslipidemia in HIV-infected patients. In conclusion, proper diagnosis and management should be offered for the prevalent metabolic complications of Korean HIV-infected patients. Further studies on risk factors for metabolic complications are needed.
Asia ; Blood Pressure ; Body Mass Index ; Cholesterol ; Cohort Studies* ; Cross-Sectional Studies ; Diagnosis ; Dyslipidemias ; Fasting ; Glucose ; HIV Infections* ; HIV* ; Humans ; Incidence ; Korea* ; Lipoproteins ; Male ; Metabolome ; Multivariate Analysis ; Obesity, Abdominal ; Prevalence ; Protease Inhibitors ; Risk Factors ; Triglycerides

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus demonstrated to be associated with human disease. Infection by the HTLV-1 can cause T-cell leukemia (ATL) in adults. HTLV-1 bZIP factor (HBZ) is a viral protein encoded by the minus strand of the HTLV-1 provirus. Among the regulatory and accessory genes of HTLV-1, HBZ is the only gene that remains intact and which is expressed consistently in all patients with ATL. Moreover, HBZ has a critical role in the leukemogenesis of ATL. Here, we review the function of HBZ in the oncogenesis of HTLV-1 and its molecular mechanism of action.
Animals ; Basic-Leucine Zipper Transcription Factors ; genetics ; metabolism ; Carcinogenesis ; HTLV-I Infections ; pathology ; virology ; Human T-lymphotropic virus 1 ; genetics ; metabolism ; Humans ; Leukemia, T-Cell ; pathology ; virology ; Retroviridae Proteins ; genetics ; metabolism

Multidrug resistant genes are highly expressed in hepatocellular carcinoma that seriousty affects the effect of chemotherapy. Screening of resistant genes from HCC cells and studying its mechanism of drug resistance will be helpful to improve the effecacy of chemotherapy for hepatocellular carcinoma. Here we described an alternative method called cyclical packaging rescue (CPR). First we constructed a retrovirus cDNA library of hepatoma cells and used it to infect fibroblasts. Then we added drugs to screen survival cells. The survival cells, stably integrated helper-free retroviral libraries, were recovered rapidly after transfection with plasmids expressing retroviral gag-pol and env genes. Through this method, retroviral RNAs were directly repackaged into new infectious virions. Recovered retroviral supernatant was then used to reinfect fresh target cells. When performed in concert with selection using functional assays, cDNAs regulating functional responses could be identified by enrichment through multiple rounds of retroviral library recovery and retransmission. Using CPR, we obtained several cDNAs. After a preliminary detection, we found Ribosomal protein S11 (RPS11), Ribosomal protein L6 (RPL6), Ribosomal protein L11 (RPL11), Ribosomal protein L24 (RPL24) possibly had drug resistant function.
Carcinoma, Hepatocellular ; genetics ; pathology ; Cell Line, Tumor ; DNA, Complementary ; Drug Resistance, Neoplasm ; genetics ; Gene Library ; Genetic Vectors ; Humans ; Liver Neoplasms ; genetics ; pathology ; Plasmids ; Retroviridae ; Ribosomal Proteins ; genetics ; metabolism ; Transfection

The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) were analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naïve and ART-experienced Asian subjects infected with human immunodeficiency virus (HIV)-1. Studies GS-US-236-102 and GS-US-236-103 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naïve subjects, comparing E/C/F/TDF versus efavirenz (EFV)/F/TDF or ritonavir-boosted atazanavir (ATV+RTV) plus emtricitabine/tenofovir DF (F/TDF), respectively. Studies GS-US-236-115 and GS-US-236-121 were randomized, open-label, 96-week long conducted in ART-experienced subjects, who switched to E/C/F/TDF from ritonavir-boosted protease inhibitors (PI+RTV)+F/TDF, or non-nucleoside reverse transcriptase inhibitors (NNRTI)+F/TDF regimens. The E/C/F/TDF appeared to have sustained efficacy and safety and was well tolerated in the small number of ART-naïve and ART-experienced Asian subjects.
Asian Continental Ancestry Group* ; Atazanavir Sulfate ; HIV* ; HIV-1* ; Humans ; Humans* ; Protease Inhibitors ; Reverse Transcriptase Inhibitors

To construct an HSV-1 vector vaccine carrying HIV-1 antigens, HIV-1 gp160, gag, protease and the expression elements were chained together, and then inserted into the internal inverted repeat sequence region of HSV-1 by bacterial artificial chromosome technology. Firstly, HIV-1 gp160 (including type B and C), gag and protease genes were cloned into pcDNA3 in series to generate the pcDNA/gBgp and pcDNA/gCgp, then the recombinant plasmids were transfected into 293FT cells, and HIV-1 antigen was detected from transfected cells by Western blotting. Then the expression cassettes from pcDNA/gBgp and pcDNA/gCgp, comprising HIV-1 antigen genes and expression elements, were cloned into pKO5/BN to generate the shuttle plasmids pKO5/BN/gBgp and pKO5/BN/gCgp. The shuttle plasmids were electroporated into E. coli cells that harbor an HSV-BAC, the recombinant bacteria were screened, and the recombinant DNA was extracted and transfected into Vero cells. The recombinant virus was purified through picking plaques, the virus' DNAs were identified by Southern blotting; HIV-1 antigen was detected from the recombinant HSV-1 infected cells by Western blotting, and the virus' replication competent was analyzed. As the results, gp160 and gag proteins were detected from 293FT cells transfected with pcDNA/gBgp and pcDNA/gCgp by Western blotting. The recombinant bacteria were generated from the E. coli electroporated with pKO5/BN/gBgp or pKO5/BN/gCgp. The recombinant HSV was purified from the Vero cells transfected with the recombinant DNA, the unique DNA fragment was detected from the genome of recombination HSV by Southern blotting; gp120 and gp41 were detected from the infected cells by Western blotting, and the recombinant HSV retained replication competent in mammalian cells. The results indicate that the recombinant HSV carrying HIV-1 gp160, gag and protease genes was generated, the virus retains replication competent in mammalian cells, and could be used as a replicated viral vector vaccine.
Animals ; Cercopithecus aethiops ; Chromosomes, Artificial, Bacterial ; DNA, Recombinant ; genetics ; DNA, Viral ; genetics ; Escherichia coli ; HIV Antigens ; genetics ; immunology ; HIV Envelope Protein gp160 ; genetics ; immunology ; HIV Protease ; genetics ; immunology ; Herpes Simplex Virus Vaccines ; immunology ; Herpesvirus 1, Human ; physiology ; Plasmids ; Transfection ; Vero Cells ; Virus Replication ; gag Gene Products, Human Immunodeficiency Virus ; genetics ; immunology