Objective:To understand the prevalence and related factors of three common chronic diseases, hyperlipidemia, hypertension and diabetes in HIV-infected persons.Methods:As of December 2023, HIV-infected persons >15 years old who are receiving antiviral therapy (ART) and follow-up in Henan Province were selected as the study objects. Questionnaires, physical examinations, and blood samples were collected to collect demographic information, ART, body weight, blood lipids, blood pressure, and blood sugar of HIV-infected persons. The logistic regression model was used to analyze the related factors of hyperlipidemia, hypertension and diabetes.Results:Among 4 023 HIV-infected patients, the prevalence rates of hyperlipidemia, hypertension, and diabetes were 64.47% (2 594/4 023), 16.80% (676/4 023), and 10.54% (424/4 023), respectively. Multivariate analysis showed that hyperlipidemia was positively associated with ≥40 years of age, overweight and obesity, two nucleoside reverse transcriptase inhibitors (NRTIs) + proteasome inhibitors (PIs) regimen and two NRTIs+ integrase inhibitor regimen, and negatively associated with low body weight. Hypertension was positively correlated with the age group ≥40 years old, family history of cardiovascular and cerebrovascular diseases, overweight and obesity, ART time ≥0.5 years, and negatively correlated with low body weight. Diabetes was positively associated with age group ≥40 years, family history of cardiovascular and cerebrovascular disease, overweight and obesity, and negatively associated with the use of two NRTIs+PIs treatment regimens.Conclusions:In 2023, the prevalence of hyperlipidemia, hypertension, and diabetes among HIV-infected people in Henan Province was relatively high, and the risk of common chronic diseases among those ≥40 years old, overweight and obese, and those with a family history of cardiovascular and cerebrovascular diseases was also relatively high. It is recommended to strengthen the prevention and management of common chronic diseases among HIV-infected people.

Objective:To understand the prevalence and related factors of three common chronic diseases, hyperlipidemia, hypertension and diabetes in HIV-infected persons.Methods:As of December 2023, HIV-infected persons >15 years old who are receiving antiviral therapy (ART) and follow-up in Henan Province were selected as the study objects. Questionnaires, physical examinations, and blood samples were collected to collect demographic information, ART, body weight, blood lipids, blood pressure, and blood sugar of HIV-infected persons. The logistic regression model was used to analyze the related factors of hyperlipidemia, hypertension and diabetes.Results:Among 4 023 HIV-infected patients, the prevalence rates of hyperlipidemia, hypertension, and diabetes were 64.47% (2 594/4 023), 16.80% (676/4 023), and 10.54% (424/4 023), respectively. Multivariate analysis showed that hyperlipidemia was positively associated with ≥40 years of age, overweight and obesity, two nucleoside reverse transcriptase inhibitors (NRTIs) + proteasome inhibitors (PIs) regimen and two NRTIs+ integrase inhibitor regimen, and negatively associated with low body weight. Hypertension was positively correlated with the age group ≥40 years old, family history of cardiovascular and cerebrovascular diseases, overweight and obesity, ART time ≥0.5 years, and negatively correlated with low body weight. Diabetes was positively associated with age group ≥40 years, family history of cardiovascular and cerebrovascular disease, overweight and obesity, and negatively associated with the use of two NRTIs+PIs treatment regimens.Conclusions:In 2023, the prevalence of hyperlipidemia, hypertension, and diabetes among HIV-infected people in Henan Province was relatively high, and the risk of common chronic diseases among those ≥40 years old, overweight and obese, and those with a family history of cardiovascular and cerebrovascular diseases was also relatively high. It is recommended to strengthen the prevention and management of common chronic diseases among HIV-infected people.

Objective:To explore the improvement of the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection and conduct safety tests including abnormal toxicity test,allergic reaction test,hemolysis and coagulation test.Methods:Ginkgo Leaf Extract and Dipyridamole Injection from 3 different manufactures(A,B and C)were tested respectively through abnormal toxicity test and acute toxicity test in mice,active systemic anaphylaxis test in guinea pigs and hemolysis test in vitro.Five mice were used in each batch for abnormal toxicity test according to the abnormal toxicity test method in general notice of the Chinese Pharmacopoeia 2020 Volume Ⅳ(1141),and 50 mice were selected in each batch for acute toxicity test to determine the median lethal dose(LD50)or maximum tol-erable dose(MTD)of Ginkgo Leaf Extract and Dipyridamole Injection,which were used to establish the method of abnormal toxicity experiment.The anaphylaxis of Ginkgo Leaf Extract and Dipyridamole Injection was evaluated by active systemic anaphylaxis test in guinea pigs,which was used to establish the method of allergic test.The hemoly-sis test of Ginkgo Leaf Extract and Dipyridamole Injection was studied by conventional tube method in vitro(macro-scopic observation)and improved hemolysis method in vitro(spectrophotometric method),which were used to establish the method of hemolysis and coagulation test.Results:① In manufacture A,the results of abnormal toxicity test were showed that LD50 was20.8 mL·kg-1and MTD was 16.5 mL·kg-1.No death or abnormal reac-tions were observed in mice tested for abnormal toxicity of 2 manufactures(B and C),and MTD was 50 and 40 mL·kg-1,respectively.②The no-observed-adverse-effect dose of Ginkgo Leaf Extract and Dipyridamole Injec-tion from 3 manufactures to guinea pig intravenous was 0.83 mL·kg-1,and no allergic reaction symptoms were observed when Ginkgo Leaf Extract and Dipyridamole Injection was diluted 4 times to challenge the sensitized guinea pigs(equivalent to human clinical dosage).③Differences were observed in the hemolytic effects of Ginkgo Leaf Extract and Dipyridamole Injection from 3 manufactures,but no obvious hemolytic reaction occurred when it was diluted 1.2 times(equivalent to 5%of the maximum clinical concentration).Conclusion:It is recommended to add abnormal toxicity test,allergic reaction test,hemolysis and coagulation test in the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection as safety test items to control the risk.The proposed method is diluting Ginkgo Leaf Extract and Dipyridamole Injection by 5 times,4 times and 1.2 times to perform abnormal toxicity test,allergic reaction test,hemolysis test and coagulation test respectively.

Objective:To explore the improvement of the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection and conduct safety tests including abnormal toxicity test,allergic reaction test,hemolysis and coagulation test.Methods:Ginkgo Leaf Extract and Dipyridamole Injection from 3 different manufactures(A,B and C)were tested respectively through abnormal toxicity test and acute toxicity test in mice,active systemic anaphylaxis test in guinea pigs and hemolysis test in vitro.Five mice were used in each batch for abnormal toxicity test according to the abnormal toxicity test method in general notice of the Chinese Pharmacopoeia 2020 Volume Ⅳ(1141),and 50 mice were selected in each batch for acute toxicity test to determine the median lethal dose(LD50)or maximum tol-erable dose(MTD)of Ginkgo Leaf Extract and Dipyridamole Injection,which were used to establish the method of abnormal toxicity experiment.The anaphylaxis of Ginkgo Leaf Extract and Dipyridamole Injection was evaluated by active systemic anaphylaxis test in guinea pigs,which was used to establish the method of allergic test.The hemoly-sis test of Ginkgo Leaf Extract and Dipyridamole Injection was studied by conventional tube method in vitro(macro-scopic observation)and improved hemolysis method in vitro(spectrophotometric method),which were used to establish the method of hemolysis and coagulation test.Results:① In manufacture A,the results of abnormal toxicity test were showed that LD50 was20.8 mL·kg-1and MTD was 16.5 mL·kg-1.No death or abnormal reac-tions were observed in mice tested for abnormal toxicity of 2 manufactures(B and C),and MTD was 50 and 40 mL·kg-1,respectively.②The no-observed-adverse-effect dose of Ginkgo Leaf Extract and Dipyridamole Injec-tion from 3 manufactures to guinea pig intravenous was 0.83 mL·kg-1,and no allergic reaction symptoms were observed when Ginkgo Leaf Extract and Dipyridamole Injection was diluted 4 times to challenge the sensitized guinea pigs(equivalent to human clinical dosage).③Differences were observed in the hemolytic effects of Ginkgo Leaf Extract and Dipyridamole Injection from 3 manufactures,but no obvious hemolytic reaction occurred when it was diluted 1.2 times(equivalent to 5%of the maximum clinical concentration).Conclusion:It is recommended to add abnormal toxicity test,allergic reaction test,hemolysis and coagulation test in the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection as safety test items to control the risk.The proposed method is diluting Ginkgo Leaf Extract and Dipyridamole Injection by 5 times,4 times and 1.2 times to perform abnormal toxicity test,allergic reaction test,hemolysis test and coagulation test respectively.

Objective:To analyze the influencing factors of genotypic drug resistance mutations in people living with human immunodeficiency virus and acquired immunodeficiency syndrome(PLWHA) who failed anti-retroviral therapy (ART) in Henan Province, in order to provide a basis for adjusting ART regimens and reducing drug resistance.Methods:PLWHA with virological failure (human immunodeficiency virus (HIV) RNA≥500 copies/mL) after receiving ART for more than 24 weeks were included in Henan Province from January 2018 to December 2022. Baseline CD4 + T lymphocyte counts, ART regimens and other clinical data were collected. HIV-1 gene subtypes and their drug resistance sequence mutations were detected in the Sixth People′s Hospital of Zhengzhou, and the sequences were submitted to the HIV Drug Resistance Interpretation System of Stanford University for comparison of test results. Genotypic drug resistance to nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI) and integrase inhibitors (INSTI) was determined. Multivariate logistic regression was used to analyze the influencing factors of drug resistance in patients with ART failure. Results:Among 982 PLWHA, the sequences of 899 cases were successfully amplified, and drug resistance was detected in 737 cases, with the drug resistance rate of 81.98%(737/899). The rates of resistance to NRTIs, NNRTIs, PIs and INSTIs were 71.97%(647/899), 79.31%(713/899), 5.23%(47/899) and 2.72%(20/734), respectively.The largest number of those who developed concomitant resistance to two classes of drugs was 588 cases (79.78%), mainly NRTI and NNRTI concomitant resistance in 583 cases (79.10%). There were 99 cases (13.43%) who developed resistance to only one class of drugs, and those who developed concurrent resistance to three classes of drugs were 48 cases (6.51%), and two cases (0.27%) were found to be resistant to all four classes of drugs mentioned above. A total of 10 HIV genotypes were detected, among which subtype B accounted for the most (59.73%(537/899)), followed by circulating recombinant form (CRF)01_AE subtype (21.91%(197/899)) and CRF07_BC subtype (9.45%(85/899)). The risk factors affecting the development of drug resistance were baseline CD4 + T lymphocyte counts, ART regimens and HIV-1 genotypes. The risk of drug resistance in patients with baseline CD4 + T lymphocyte counts <100/μL was 4.55 times (95% confidence interval ( CI) 2.69 to 7.70) higher than patients with CD4 + T lymphocyte counts≥250/μL, the risk of drug resistance in patients using 2NRTIs+ NNRTI regimen was 4.51 times (95% CI 1.75 to 11.63) higer than those using 2NRTIs+ INSTI regimen, and patients infected with B and CRF01_AE subtype was 2.18 times (95% CI 1.10 to 4.29) and 2.70 times (95% CI 1.26 to 5.78) higer than those with CRF07_BC subtype, respectively. Conclusions:The incidence of genotypic drug resistance in PLWHA with ART failure in Henan Province is high. Low baseline CD4 + T lymphocyte counts, 2NRTIs+ NNRTI regimens, and genotype B and CRF01_AE are risk factors for drug resistance in PLWHA.

Objective:To understand the clinical characteristics of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients with renal injury after antiviral therapy in Henan Province, and to explore the risk factors of renal injury.Methods:A cross-sectional study was conducted to investigate HIV infection/AIDS patients receiving antiviral therapy in Zhengzhou Sixth People′s Hospital, Anyang Fifth People′s Hospital, Hebi Third People′s Hospital, Luo Yang Zhoushan Hospital and Lankao Central Hospital in Henan Province from April 1 to September 30, 2023. The clinical information including basic data, antiviral therapy regimens and comorbidities, and laboratory test results (blood urea nitrogen, serum creatinine, blood uric acid, urine routine, urine microalbumin, urine α 1-microglobulin (α 1-MG), urine β 2-microglobulin (β 2-MG), urine retinol binding protein (RBP), urine creatinine, HIV viral load, CD4 + T lymphocyte count) were collected. Multivariate binary logistic regression was used to analyze independent risk factors for renal injury. Results:A total of 2 526 HIV infection/AIDS patients were included, with the age of (45.52±14.28) years and 2 156 (85.4%) males. The main route of transmission was sexual transmission (91.6%, 2 314/2 526). The duration of antiviral therapy was 5.00(2.92, 8.00) years. Tenofovir (TDF)+ lamivudine (3TC)+ non-nucleoside reverse transcriptase inhibitors (NNRTI) accounted for 55.3%(1 396/2 526) of the current antiviral therapy regimen. The percentage of HIV viral load <50 copies/mL was 93.0%(2 350/2 526). The CD4 + T lymphocyte count was 476(337, 645)/μL. There were 156 patients (6.2%) complicated with hepatitis B and/or hepatitis C, 205 patients (8.1%) with diabetes, 379 patients (15.0%) with hyperlipidemia, and 189 patients (7.5%) with hyperuricemia. A total of 1 040 patients (41.2%) with renal injury were found through renal function test, including 355 cases (14.1%) with estimated glomerular filtration rate (eGFR) <60 mL/(min·1.73 m 2) or urine protein positive or urine albumin creatine ratio (UACR) ≥30 mg/g, 682 patients (27.0%) with pure tubular injury presented with only positive for urinary α 1-MG, urinary β 2-MG, or urinary RBP. eGFR< 60 mL/(min·1.73 m 2) was found in 71 cases (2.8%), eGFR from 60 to 89 mL/(min·1.73 m 2) was found in 509 cases (20.2%), and eGFR≥90 mL/(min·1.73 m 2) was found in 1 946 cases (77.0%). A total of 138 patients (5.5%) were identified as having combined chronic kidney disease (CKD). Among them, 110 patients (79.7%) were in CKD stages 1 to 2, and 117 patients (84.8%) were in urinary albumin A2 grade. Multivariate analysis of 355 patients with renal injury who had eGFR<60 mL/(min·1.73 m 2) or positive urine protein in urine routine or UACR ≥30 mg/g showed that ages of 50 to 69 years old (odds ratio( OR)=2.189, 95% confidence interval ( CI) 1.333 to 3.596, P=0.002)), ≥70 years old ( OR=5.190, 95% CI 2.912 to 9.248, P<0.001), female ( OR=1.685, 95% CI 1.241 to 2.286, P=0.001), combined opportunistic infection ( OR=2.521, 95% CI 1.567 to 4.056, P<0.001), combined hepatitis B ( OR=1.962, 95% CI 1.110 to 3.467, P=0.020), combined hepatitis C ( OR=1.883, 95% CI 1.043 to 3.400, P=0.036), combined diabetes ( OR=2.703, 95% CI 1.911 to 3.821, P<0.001), using TDF for two to four years ( OR=1.674, 95% CI 1.103 to 2.459, P=0.015), using TDF for greater than or equal to five years ( OR=1.880, 95% CI 1.287 to 2.746, P=0.001), using TDF combined with lopinavir/ritonavir (LPV/r) ( OR=3.610, 95% CI 2.273 to 5.734, P<0.001) and using TDF combined with non-LPV/r ( OR=1.495, 95% CI 1.036 to 2.157, P=0.031) were the risk factors of renal injury. Conclusions:There is a high proportion of renal injury among HIV infection/AIDS patients after antiviral therapy in Henan Province, including CKD and simple renal tubular injury. Older age, female, comorbidities, and long-term use of TDF are risk factors for renal injury.

Humans ; Mutation/genetics* ; HIV Infections/drug therapy* ; Drug Resistance ; Treatment Failure ; China ; Drug Resistance, Viral/genetics*

ObjectiveTo evaluate the lipid-lowering activity of Quansanqi tablets（QSQ）， an innovative new drug of Panax notoginseng. MethodMice and golden hamsters were used to establish a hyperlipidemia model by injecting egg yolk milk and feeding high-fat diets. The levels of total cholesterol （TC），triglyceride （TG），low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected， and liver function indicators ［alanine aminotransferase （ALT）， aspartate amino-transferase （AST）， and alkaline phosphatase （ALP）］ of golden hamsters were detected. Hematoxylin-eosin （HE） staining was used to observe the degree of liver injury. In the experiments， a normal group， a model group， an atorvastatin calcium group， and low-， medium-， and high-dose QSQ groups （0.32， 0.64， 1.28 g·kg^-1 for mice， and 0.16， 0.32， 0.64 g·kg^-1 for golden hamsters） were set up. ResultCompared with the normal group， the acute hyperlipidemia model mice showed increased TC， TG， and LDL-C levels （P<0.01）， and the hyperlipidemia model mice showed increased TC and LDL-C levels （P<0.01）. Additionally， the hyperlipidemia model golden hamsters showed increased serum TC， TG， LDL-C， ALT， AST， and ALP levels （P<0.05， P<0.01）. HE staining indicated the presence of fat accumulation in the liver， accompanied by inflammatory reactions. Compared with the model group， QSQ of various doses could reduce TC， TG， and LDL-C levels in acute hyperlipidemia model mice （P<0.05， P<0.01）， and the high-dose QSQ could reduce TC and LDL-C levels （P<0.01） and increase HDL-C level （P<0.05） in hyperlipidemia model mice， as well as reduce TC， TG， and LDL-C levels in hyperlipidemia model golden hamsters （P<0.05， P<0.01）， especially in the first two weeks. In addition， atorvastatin calcium could further increase ALT， AST， and ALP levels （P<0.05， P<0.01） and aggravate liver function damage， while low-dose QSQ could reduce ALT， AST， and ALP （P<0.05）， and medium- and high-dose QSQ did not cause further liver function damage. ConclusionQSQ have a significant lipid-lowering effect on different hyperlipidemia model animals and can improve liver function and liver injury.

Objective:To analyze the drug resistance characteristics of HIV/AIDS patients in Henan Province with antiretroviral treatment (ART) failure through the genotypic drug resistance detection.Methods:Blood samples were collected from HIV/AIDS patients who received ART for more than 6 months with viral loads ≥1 000 copies/ml in 18 cities of Henan from January 2018 to May 2021. The genotypic drug resistance detection was conducted by using an In-house drug resistance detection method. The drug resistance mutation (DRM) and antiretroviral susceptibility were analyzed by submitting the determined sequences to the Stanford HIV-1 drug resistance database. The information about patients' demographic characteristics and antiviral treatment data were collected.Results:A total of 887 HIV/AIDS patients with ART failure, 812 sequences were successfully amplified with the success rate of 91.54%. In the 812 patients, 676 were drug resistant (83.25%, 676/812). The drug resistance ratesto nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) were 73.40% (596/812), 80.54% (654/812), 5.54% (45/812), and 2.56% (17/663), respectively. There were significant differences in drug resistance rates among four types of drugs ( χ2=1 686.34, P<0.001). The drug resistance rate to two drugs was 66.38% (539/812), and the drug resistance rate to three drugs was 5.79% (47/812). A total of 9 subtypes of HIV-1were detected, in which subtype B accounted for 59.61%(484/812), followed by subtype CRF01_AE (22.17%, 180/812) and subtype CRF07_BC (9.48%, 77/812). There were significant differences in drug resistance rate among different subtypes ( χ2=21.33, P=0.001). Among NRTIs related mutation sites, the DRM rate of M184V/I was highest (63.42%, 515/812), followed by K65R (27.46%, 223/812). The top three DRM rates were detected for K103N/S (34.98%, 284/812), G190A/S (26.11%, 212/812) and V106M/I (24.63%, 200/812) among NNRTIs related mutation sites, and M46I (4.31%, 35/812), V82A/F (3.82%, 31/812), and I54V/MV (3.69%, 30/812) among PIs related mutation sites. While among INSTIs related mutation sites, E157Q/EQ had the highest DRM rate (3.47%, 23/663), followed by R263K (0.75%, 5/663) and G140A (0.75%, 5/663). The resistance to lamivudine and emtricitabine of NRTIs was at high-level (65.52%, 532/812), and the resistance to nevirapine (77.46%, 629/812) and efavirenz (71.18%, 578/812) of NNRTIs was also at high-level. The medium/high-level resistance to lopinavir/ritonavir of PIs was only 4.19% (34/812), the medium/high-level resistance to elvitegravir and raltegravir of INSTIs was 1.66% (11/663) and 1.21% (8/663), respectively, and no high-level resistance to bictegravir or dolutegravir was found. Conclusions:The drug resistance in HIV/AIDS patients with ART failure was high in Henan, characterized by high drug resistance rates to NRTIs and NNRTIs, and diverse and complex resistance mutations. So high resistance barrier ART-regimens were recommended, and the viral load monitoring and drug resistance testing after ART should be strengthened.

Objective:To analyze the correlation between human immunodeficiency virus (HIV)-1 reservoir and poor immune reconstitution of HIV/acquired immunodeficiency syndrome (AIDS) patients, and to investigate the influence of HIV-1 reservoir on the immune reconstitution.Methods:Cross-sectional survey was conducted to measure HIV-1 RNA and T lymphocyte subsets from 219 patients with HIV/AIDS who had been treated with anti-retroviral therapy (ART) for more than two years with HIV RNA lower than the limit of detection. Among them, there are 195 patients from the Sixth People′s Hospital of Zhengzhou, 12 patients from Shangqiu Municipal Hospital and 12 patients from Zhoukou Infectious Diseases Hospital. Peripheral blood mononuclear cells (PBMC) were collected and HIV-1 DNA was detected. The measurement data of normal distribution were analyzed by two independent sample t-test. The measurement data of skewness distribution were analyzed by rank sum test. Spearman′s rank correlation was used for correlation analysis. Receiver operating characteristic curve (ROC) was used to predict the predictive value of occurrence of poor immune reconstitution AIDS patients. Results:There were 121 patients with poor immune reconstitution and 98 patients with healthy immune reconstitution. HIV-1 DNA was (2.50±0.52) copies/1×10 6 PBMC in the group with poor immune reconstitution, which was significantly higher than the healthy immune reconstitution group ((2.11±0.66) copies/1×10 6 PBMC, t=4.78, P<0.001). The CD4 + T lymphocyte counts in the group with poor immune reconstitution was 192(139, 227)/μL, which was lower than that in the healthy immune reconstitution group (573(457, 730)/μL). The difference was statistically significant ( Z=12.68, P<0.001). HIV-1 DNA was reversely correlated with CD4 + T lymphocyte counts and CD4 + /CD8 + T lymphocyte ratio (after adjusting the influence of age and ART time, r=-0.277 and -0.316, respectively, both P<0.001). The area of ROC curve for HIV-1 DNA to predict poor immune reconstitution was 0.679(95% confidence interval ( CI) 0.604 to 0.750). The HIV-1 DNA threshold value was 100 copies/1×10 6 PBMC with the sensitivity of 90.13% and specificity of 42.91%. The area of ROC curve of CD4 + /CD8 + T lymphocyte ratio to predict poor immune reconstitution was 0.905 (95% CI 0.863 to 0.942). The threshold value of CD4 + /CD8 + T lymphocyte ratio was 0.536 with the sensitivity of 77.68% and specificity of 89.84%. Conclusions:There is correlation between HIV-1 DNA and poor immune reconstitution in HIV/AIDS patients. The value of HIV-1 DNA higher than 100 copies/1×10 6 PBMC and CD4 + /CD8 + T lymphocyte ratio lower than 0.536 could be used as predictor of poor immune reconstitution.