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.

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.

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

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.

Objective:To investigate the drug resistance of patients with acquired immunodeficiency syndrome (AIDS) who failed antiviral therapy.Methods:A total of 156 AIDS patients with antiviral therapy failure at the Sixth People′s Hospital of Zhengzhou from October 2017 to December 2018 were selected. The human immunodeficiency virus (HIV)-1 ViroSeq? genotyping method was used for the detection of HIV resistance, and Stanford University HIV drug resistance database (http: ∥hivdb.stanford.edu/) was used for testing results comparison.Results:Among the 156 AIDS patients with antiviral therapy failure, 122(78.21%) developed drug resistance. One hundred and six (67.95%) cases were multi-resistant to nucleoside reverse transcriptase inhibitor (NRTI), among which, 104 (66.67%) were resistant to lamivudine, emtricitabine and abacavir. One hundred and eighteen (75.64%) were resistant to non-nucleoside reverse transcriptase inhibitor (NNRTI), and 118 (75.64%) were multi-resistant to efavirenz and nevirapine. And seven (4.49%) were resistant to protease inhibitor (PI). There were 16 resistant sites for NRTI, with 87 (71.31%) most frequent M184V/I mutations. There were 13 resistant sites for NNRTI, with 49 (40.16%) K103N/R mutations. There were 11 resistant sites for PI, with 49 (40.16%) A71V/T mutations. The antiviral drugs lamivudine and emtricitabine were moderately and highly resistant in 102 (83.61%) cases, efavirenz and nevirapine were moderately and highly resistant in 117 (95.90%) cases. Once drug resistance developed, these drugs were likely to be moderate or high resistance. There were 29 (23.77%), 48 (39.34%), and five (4.10%) cases were resistant to zidovudine, tenofovir and lopinavir/ritonavir, respectively. The resistance barrier of these drugs was relatively high.Conclusion:The incidence of drug resistance in patients with AIDS treatment failure is high, and multi-drug resistance is serious with various sites of drug resistance.

Objective To study the survival status and the prognostic factors of aquired immune deficiency syndrome (AIDS) patients under the highly active antiretroviral therapy (HAART) in He'nan Province.Methods Survival data of AIDS patients were collected from the National HAART reporting system between 2005 and 2015,and analyzed using SPSS 23.0 software.Results A total of 38 143 AIDS cases were enrolled in this study.The cumulative survival rate of patients under antiretroviral therapy after 1-5 years were 95％,91％,89％,86％ and 85％,respectively.The cumulative death cases were 5 704 and the total mortality was 3.68/100 person years (5 704/155 060 person years).A total of 1 975 cases died within a year with a percentage of 34.62％.Cox proportional hazard regression model analysis indicated that the hazard ratioc (HR [95％CI]) of death in patients with age of 40-49 years,50-59 yrears,60-69 yrears and ≥70 years groups compared to those with age ＜30 years group were 1.49 (1.22-1.80),1.88 (1.55-2.28),2.82 (2.32 3.42) and 4.60 (3.75-5.65),respectively.The HR (95％ CI) of death in patients with CD4 T cell counts ＜50 cells/μL,50-199 cells/μL,200-349 cells/μL groups compared to those of ≥350 cells/μL group were 3.28 (2.98-3.61),2.30 (2.09-2.53) and 1.39 (1.25-1.54),respectively.Male (HR-1.35,95％CI:1.28-1.42) and not switching to second line therapy (HR=4.41,95％CI:4.12-4.73) were the risk factors of death.Compared to sex transmission,blood transmission was the risk factors of death in AIDS patients.Conclusions The initiation of early HAART and timely switching to second line therapy for AIDS patients are key to prolong the survival time and to reduce AIDS related death.

Objective To discuss the epidemiology and clinical characteristics of AIDS in some part of Henan regions.Methods Retrospective analysis was conducted based on the clinical and epidemic information collected from AIDS patients who were treated in the Sixth People's Hospital of Zhengzhou between 2006 and 2015 in He'nan province.Results Between 2006 and 2015,the number of hospitalization increased every year.The average growth rate was 20.31％.The average age of patients was (43.91 ± 13.56) years old.The patients from 40 to 60 years old group occupied 54.06％ of total patients,and 71.12％ of patients were farmers.During 2006 to 2015,the propagation path changed a lot.Before 2008,blood transmission was the major propagation path (72.72％),but after 2013,the major propagation path was sexual activity (59.69％).40.41％ of patients were infected by two or more opportunistic infections.The top five opportunistic infections were bacterial pneumonia (32.68％),tuberculosis (19.29％),fungal infection (18.65％),pneumocystis carinii pneumonia (12.96％),extra pulmonary tuberculosis (7.45％).The death rate was 5.79％.The number of CD4 cells in peripheral blood was closely related to the severity of illness.Conclusion Early anti-virus treatment and opportunistic infection control are key factors to relieve the severity of illness and reduce the death rate.

Objective To evaluate the effect of second-line antiretroviral treatment (ART) on human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and provide reference for subsequent HIV/AIDS treatment.Methods Two hundred and twenty-eight HIV/AIDS patients received second-line ART during January 2011 and December 2015 in Zhengzhou were included.Two hundred and forty-eight who received first-line ART during this period were randomly enrolled as control group.CD4+ T cell count and HIV RNA load before and after treatment were compared with x2 test and t test when appropriate.Results There were 228 patients (137 male and 91 female) in the second-line ART group and 248 patients (176 male and 72 female) in the control group.In second-line ART group, CD4+ T cells increased from (274±200)/μL to (476±261)/μL after an average treatment of (39.5±18.8) months.The difference was statistically significant (t=12.91, P<0.05).In control group, CD4+T cells increased from (251±199)/μL to (470±233)/μL after an average treatment of (35.7±14.7) months.The difference was statistically significant (t=14.60, P<0.05).CD4+ T cells showed no statistical difference between two groups regardless of treatment (t=1.25 and 0.26, respectively, both P>0.05).During the treatment, the rates of immunological failure were 9.6% (22/228) in second-line ART group and 12.9% (32/248) in the control group.There was no statistical difference between two groups (x2=1.251, P>0.05).Complete viral inhibition rates were 83.3% (190/228) in second-line ART group and 88.7% (220/248) in control group with no statistical difference (x2=2.881, P>0.05).Conclusions Second-line ART regimen has equivalent treatment efficacy with first-line ART.To achieve a better outcome, second-line ART regimen should be selected as an alternative option when first-line regimen fails.Compliance is the key to guarantee the success of antiviral therapy.