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

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*

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

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

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

OBJECTIVETo study the condition of HIV-1 drug resistance mutation among failures of first-line antiretroviral therapy in Henan province.

METHODThe sub platform of China's legal infectious disease monitoring information reporting system-HIV/AIDS integrated prevention and control data information management system was used to collect the information of patients experiencing first-line antiretroviral treatment failure (virus load ≥ 1 000 copies/ml) more than one year among nine cities of Henan in 2011. A total of 40 cases with no information and 212 cases with incomplete drug resistance results were deleted, and 1 922 cases were included in this study and genotype resistance testing was carried out. Non-conditional logistic regression analysis was used to analyse the influencing factors of drug resistance mutation.

RESULTSA total of 1 922 cases were included in the analysis. 1 039 cases were males, 833 cases were females, the age was (45.7 ± 12.1) years, 82.73% (1 590) were married, and 87.93% (1 690) were transmitted by blood. 64.20% (1 234) patients acquired drug resistance. Nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) resistance mutations were found in 62.59% (1 203), 49.74% (956) and 0.94% (18) of subjects, respectively. 42.09% (809) of patients harbored NRTI and NNRTI resistance mutations synchronously. ≥ 1TAM was the most commonly emerged NRTI resistance mutation (41.94% (806)), the prevalences of TAM-1 and TAM-2 were 8.48% (163) and 4.24% (81), respectively. K65R/N and Q151M complex existed in 23 and 4 patients, respectively. K103N/S was the most commonly emerged NNRTI resistance mutation (34.32% (659)). Non-conditional logistic regression analysis showed that, factors associated with high drug resistance were the following: transmitted by mother to child (OR = 9.05, 95% CI: 1.14-72.12), clinical stage was IV (OR = 1.70, 95% CI: 1.09-2.66) and 5-year-treated (OR = 1.59, 95% CI: 1.03-2.47). Factors associated with low drug resistance were the following: 1-year-treated (OR = 0.19, 95% CI: 0.13-0.27).

CONCLUSIONComplex patterns of HIV-1 drug resistance mutations were identified among individuals experiencing failure of first-line antiretroviral therapy in Henan province. Factors associated with high drug resistance were lived in Luohe, Shangqiu, Nanyang, Xinyang, transmitted by mother to child, clinical stage was IV, and 5-year-treated.

Adult ; China ; Drug Resistance, Viral ; genetics ; Female ; Genotype ; HIV Infections ; drug therapy ; HIV-1 ; drug effects ; genetics ; Humans ; Infectious Disease Transmission, Vertical ; Male ; Middle Aged ; Prevalence ; Protease Inhibitors ; therapeutic use ; Reverse Transcriptase Inhibitors ; therapeutic use

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

Eleven compounds were isolated from the culture of Streptomyces sp. CPCC 202950 by a combination of various chromatographic techniques including column chromatography over macroporous resin HP-20, MCI, and reversed-phase HPLC. Their structures were identified as 1H-pyrrole-2-carboxamide(1),5'-deoxy-5'-methylthioinosine(2), vanillamide(3), trans-3-methylthioacrylamide(4), 1,2,3,4-Tetraydro-1H-pyrido[3,4-b]indole-3-carboxylic acid(5), cyclo(L-pro-L-tyr) (6), N-[2-(4-hydroxyphenyl)]ethylacetamide(7), benzamide (8), cyclo ('L-leucyl-trans-4-hydroxy-L-proline)(9), cyclo-(Phe-Gly) (10), and tryptophan (11). Among them, compounds 1 and 2 were new natural products. In the preliminary assays, none of the compounds exhibited obvious inhibition of HIV-1 protease activity (IC50 > 10 micromol x L(-1)).
Culture Media ; chemistry ; metabolism ; HIV Protease ; analysis ; HIV Protease Inhibitors ; chemistry ; isolation & purification ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization ; Streptomyces ; chemistry ; metabolism

BACKGROUND: The combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has been the first choice nucleoside reverse transcriptase inhibitor (NRTI) according to many reliable antiretroviral treatment (ART) guidelines because of its high efficacy. However, TDF-related renal toxicity reported in Western countries is a challenging issue regarding clinical use. We conducted this study to evaluate the incidence and characteristics of an acute increase in serum creatinine (Cr) level > 1.5 mg/dL among TDF/FTC-based highly active antiretroviral treatment (HAART)-treated patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 205 HIV-infected patients treated with TDF/FTC-containing regimens between 1 February 2010 and 30 April 2014. Three groups of TDF/FTC + ritonavir-boosted protease inhibitor (PI/r), TDF/FTC + non-nucleoside reverse transcriptase inhibitor (NNRTI), and TDF/FTC + integrase strand transfer inhibitor (INSTI), and three PI/r subgroups of TDF/FTC + lopinavir (LPV)/r, TDF/FTC + atazanavir (ATV)/r, TDF/FTC + darunavir (DRV)/r were evaluated. RESULTS: A total 136 patients (91 in the TDF/FTC + PI/r group, 20 in the TDF/FTC + NNRTI group and 25 in the TDF/FTC + INSTI group) were included in the statistical analysis. Four cases (4.9%; all in the TDF/FTC + PI/r group) among 136 patients showed an acute increase in serum Cr more than 1.5 mg/dL, so the overall incidence was 2.8 cases per 100 patient-years. One case was a patient treated with TDF/FTC + LPV/r, and the others were treated with TDF/FTC + ATV/r. No case of an acute increase in serum Cr was observed in the TDF/FTC + DRV/r group. The incidence of serum Cr increase more than 1.5 mg/dL in TDF/FTC + PI/r group was 4.0 cases per 100 patient-years. CONCLUSION: Although only a small number of patients were evaluated retrospectively from a single center, the TDF/FTC + PI/r regimen may have been related with relatively higher tendency of increment of serum Cr level. These findings reinforce the importance of close follow-ups of HIV-infected patients treated with the TDF/FTC + PI/r regimens.
Anti-Retroviral Agents ; Antiretroviral Therapy, Highly Active* ; Atazanavir Sulfate ; Creatinine* ; Darunavir ; Emtricitabine ; Follow-Up Studies ; HIV ; Humans ; Incidence* ; Integrases ; Lopinavir ; Medical Records ; Protease Inhibitors ; Retrospective Studies ; RNA-Directed DNA Polymerase ; Tenofovir