OBJECTIVE: This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China. METHODS: A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database. RESULTS: A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs. CONCLUSION The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
Humans ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV-1/genetics* ; Cross-Sectional Studies ; Phylogeny ; Anti-HIV Agents/therapeutic use* ; Drug Resistance, Viral/genetics* ; HIV Infections/epidemiology* ; Mutation ; China/epidemiology* ; Prevalence ; Genotype

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 investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ²=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ²=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology* ; Cities ; Drug Resistance ; Drug Resistance, Viral/genetics* ; Female ; Genotype ; HIV Infections/epidemiology* ; HIV Seropositivity/drug therapy* ; HIV-1/genetics* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Reverse Transcriptase Inhibitors/therapeutic use* ; Sexual and Gender Minorities

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

Objective: To understand the epidemiological characteristics of one large HIV molecular transmission cluster in Jiaxing city, Zhejiang province, 2017 in order to select those people under high-risk and providing basis for programs on prevention. Methods: During 2017, newly diagnosed HIV/AIDS cases in this city were recruited. Plasma samples were collected from subjects, followed by RNA extraction, RT-PCR and nest-PCR for pol gene amplification, before being sequenced and aligned. Mega 6.0 software was used to construct phylogenetic tree, and Cytoscape 3.6.0 software was used to identify HIV molecular transmission clusters. Cases within the large transmission clusters were investigated, using a field-epidemiology-questionnaire. Data related to socio-demographics and previous sexual behaviors were collected and EpiData 3.0 and SPSS 20.0 software were used. Results: In the large transmission cluster with subtype identified as CRF07_BC, in Jiaxing, 2017, 26 cases of the total 30 cases were investigated. A total of 80.8% (21/26) could be identified as newly infected within the last two years and 30.8%(8/26) could be identified as newly infected within the last one year, including 22 cases infected locally. Among several infected cases who were at age 45 years or older, they admitted that they had experienced unprotected sexual contacts in local city for long time and having had more than 10 disclosed sexual contacts within the last two years at the local venues. Conclusions: This molecular cluster had been formed and scaled up quickly in recent two years, it has played an important role in promoting and scaling up the HIV transmission. Three cases identificed as high risk played an importantrde role in scaling up this cluster.
Amplified Fragment Length Polymorphism Analysis ; China/epidemiology* ; Genes, pol ; Genotype ; HIV Infections/transmission* ; HIV-1/isolation & purification* ; Humans ; Molecular Epidemiology ; Phylogeny ; Polymerase Chain Reaction ; RNA, Viral/blood* ; Sexual Behavior ; pol Gene Products, Human Immunodeficiency Virus

To determine the inhibitory effect of endophytic fungi from Dysosma versipellis on HIV-1 IN-LEDGF/p75 interaction,the protein-protein interaction between human immunodeficiency virus type 1( HIV-1) integrase and lens epithelial growth factor p75 protein( LEDGF/p75) was used as a target. The homogeneous time-resolved fluorescence( HTRF) technique was used in the inhibitory activity assay. The results showed that eight endophytic fungi with anti-IN-LEDGF/p75 interaction activity were screened out from fifty-three strains with different morphological characteristic. Among them,106 strain showed strong inhibitory activity against HIV-1 IN-LEDGF/p75 interaction with IC50 value of 5. 23 mg·L-1,and was identified as a potential novel species of Magnaporthaceae family by the analyses of ITS-rDNA,LSU and RPB2 sequences data. This study demonstrated that potential natural active ingredients against the HIV-1 IN-LEDGF/p75 interaction exist in the endophytic fungi of D. versipellis. These results may provide available candidate strain resources for the research and development of new anti-acquired immunodeficiency syndrome drugs.
Berberidaceae ; microbiology ; Endophytes ; Fungi ; chemistry ; HIV Integrase ; metabolism ; HIV-1 ; drug effects ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Protein Binding

Objective: To understand prevalence and transmission of transmitted drug resistance (TDR) among HIV infected men who have sex with men (MSM) in Tianjin from 2014 to 2017. Methods: A total of 225 blood samples were collected from HIV infected MSM in Tianjin from 2014 to 2017. Pol gene fragments were obtained by viral RNA extraction and nested PCR amplification. Phylogenetic and drug resistance analyses were conducted. Results: A total of 205 samples were successfully sequenced and analyzed. Based on pol sequences, 53.2% (109/205), 28.8% (59/205), 10.2% (21/205), 4.9% (10/205) and 2.9% (6/205) of the samples were positive for HIV subtypes CRF01_AE, CRF07_BC, B, CRF55_01B and unique recombinant forms (URFs). Twenty transmission clusters, including 75 sequences, were identified and 62.5% (10/16) of sequences with TDR were in 5 clusters. The prevalence of TDR was 7.8% between 2014 and 2017. The annual prevalence rate increased from 3.9% (2/51) in 2014, 5.7% (3/53) in 2015, 9.6% (5/52) in 2016 to 12.2%(6/49) in 2017, the difference was not significant (χ(2)=2.504, P=0.127). CRF01_AE and B strains had high TDR prevalence (3.4%, 7/205) and (2.9%, 6/205), respectively. The TDR mutation was mainly NNRTIs, the TDR prevalence was 6.3% (13/205). In contract, the TDR prevalence of NRTIs and PIs were 1.5% (3/205) and 1.0% (2/205) respectively. Conclusion: Results from this study suggested that the prevalence of HIV-1 TDR strains in MSM was serious in Tianjin. It is necessary to take effective prevention and control measures.
China ; Drug Resistance, Viral/genetics* ; Genes, pol ; Genotype ; HIV Infections/transmission* ; HIV Reverse Transcriptase/genetics* ; HIV Seropositivity/genetics* ; HIV-1/isolation & purification* ; Homosexuality, Male/statistics & numerical data* ; Humans ; Male ; Mutation ; Phylogeny ; Polymerase Chain Reaction ; Prevalence ; RNA, Viral/genetics* ; pol Gene Products, Human Immunodeficiency Virus/genetics*

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*

BACKGROUND: Dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG/DRV/c) is reasonable alternative option for patients with existing resistance and/or intolerance to nucleoside reverse transcriptase inhibitors (NRTIs). MATERIAL AND METHODS: All patients who switched to DTG/DRV/c among treatment-experienced patients with human immunodeficiency virus (HIV) in a tertiary university hospital were selected. We analyzed the effectiveness, safety, and tolerability based on serial laboratory data and clinical findings. The primary endpoint was defined as the proportion of patients with plasma HIV RNA below 50 copies/mL at week 48 after switch. Secondary endpoints included evaluation of safety and tolerability. RESULTS: Thirty-one patients were retrospectively analyzed. The main reasons for the change to DTG/DRV/c were treatment failure in 13 patients (41.9%), simplification in 12 patients (38.7%), and adverse drug reaction in 6 patients (19.4%). Among the 13 patients who switched owing to treatment failure, the proportion of patients in whom the viral loads were suppressed to less than 50 copies/mL increased from 0% at baseline to 45% at 4 weeks, 50% at 12 weeks, 50% at 24 weeks, and 66.7% at 48 weeks. HIV virus levels decreased and CD4⁺ T cell counts increased during the follow-up period. In non-treatment failure patients (18 patients), the levels of viral suppression and CD4⁺ T cells were maintained. There were no significant differences in renal function, liver function, glucose levels, and lipid profile before and after regimen changes. The tolerability was very good: 30 patients (96.8%) tolerated the drugs well and only 1 patient discontinued owing to no improvement in renal insufficiency. Two patients (6.4%) in treatment failure group failed to reach viral suppression. CONCLUSION: The use of DTG/DRV/c in HIV treatment-experienced patients appears to be a very good regimen for switch therapy that is effective and well tolerated, without significant adverse drug reaction.
Cell Count ; Cobicistat ; Darunavir* ; Drug-Related Side Effects and Adverse Reactions ; Follow-Up Studies ; Glucose ; HIV* ; Humans ; Humans* ; Liver ; Plasma ; Renal Insufficiency ; Retrospective Studies ; Reverse Transcriptase Inhibitors ; RNA ; T-Lymphocytes ; Treatment Failure ; Viral Load