Diagnostic performance evaluation of urine HIV-1 antibody rapid test kits in a real-life routine care setting in China.

OBJECTIVES: To evaluate the diagnostic performance of urine HIV antibody rapid test kits in screening diverse populations and to analyse subjects' willingness regarding reagent types, purchase channels, acceptable prices, and self-testing. DESIGNS: Diagnostic accuracy studies PARTICIPANTS: A total of 2606 valid and eligible samples were collected in the study, including 202 samples from female sex workers (FSWs), 304 persons with injection drug use (IDU), 1000 pregnant women (PW), 100 subjects undergoing voluntary HIV counselling and testing (VCT) and 1000 students in higher education schools or colleges (STUs). Subjects should simultaneously meet the following inclusion criteria: (1) being at least 18 years old and in full civil capacity, (2) signing an informed consent form and (3) providing truthful identifying information to ensure that the subjects and their samples are unique. RESULTS: The sensitivity, specificity and area under the curve (AUC) of the urine HIV-1 antibody rapid test kits were 92.16%, 99.92% and 0.960 (95% CI: 0.952 to 0.968, p<0.001), respectively, among 2606 samples collected during on-site screenings. The kits showed good diagnostic performance in persons with IDU (AUC, 1.000; 95% CI, 1.000 to 1.000, p<0.001), PW (AUC, 0.999; 95% CI, 0.999 to 1.000, p<0.001) and FSWs (AUC, 1.000; 95% CI, 1.000 to 1.000, p<0.001). The AUC of the urine reagent kits in subjects undergoing VCT was 0.941 (95% CI: 0.876 to 0.978, p<0.001). The 'acceptable price' had the greatest influence on STUs (Pi=1.000) and PW (Pi=1.000), the 'purchase channel' had the greatest influence on subjects undergoing VCT (Pi=1.000) and persons with IDU (Pi=1.000) and the 'reagent types' had the greatest influence on FSWs (Pi=1.000). CONCLUSIONS: The rapid urine test kits showed good diagnostic validity in practical applications, despite a few cases involving misdiagnosis and underdiagnosis.

[Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi].

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.

Short-term toxicity assessment of combined use of zidovudine, lamivudine and lopinavir/ritonavir in vitro and in vivo.

INTRODUCTION: A combination of zidovudine (AZT), lamivudine (3TC) and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother-to-child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity. METHOD: An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28-day feeding test was conducted to assess the potential subacute toxicity. RESULTS: In mice, the LD50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose-dependent manner in mice (P < 0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high-dose group was lower than that in the control group (P < 0.05); the relative weights of the liver, kidney, spleen and brain increased (P < 0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high-dose group. The haemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high-dose group increased (P < 0.05). The total protein, albumin, cholesterol and blood glucose levels of male and female rats in the high-dose group were significantly decreased (P < 0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium- and high-dose groups increased significantly (P < 0.05). CONCLUSION: The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions.

Distinct Rates and Transmission Patterns of Major HIV-1 Subtypes among Men who Have Sex with Men in Guangxi, China.

The diversity and transmission patterns of major HIV-1 subtypes among MSM population in Guangxi remains unknown. Understanding the characteristics is crucial for effective intervention strategies. Between 2016 and 2021, we recruited individuals newly diagnosed with HIV-1 from MSM population in Guangxi. HIV-1 pol region was amplified and sequenced, and constructed molecular network, assessed clustering rate, cluster growth rate, spatial clustering, and calculating the basic reproductive number (R0) based on sequences data. We identified 16 prevalent HIV-1 subtypes among Guangxi MSM, with CRF07_BC (53.1%), CRF01_AE (26.23%), and CRF55_01B (12.96%) predominating. In the network, 618 individuals (66.17%) formed 59 clusters. Factors contributing to clustering included age < 30 years (AOR = 1.35), unmarried status (AOR = 1.67), CRF07_BC subtype (AOR = 3.21), and high viral load (AOR = 1.43). CRF07_BC had a higher likelihood of forming larger clusters and having higher degree than CRF01_AE and CRF55_01B. Notably, CRF07_BC has higher cluster growth rate and higher basic reproductive number than CRF01_AE and CRF55_01B. Our findings underscore CRF07_BC as a prominent driver of HIV-1 spread among Guangxi's MSM population, highlighting the viability of targeted interventions directed at specific subtypes and super clusters to control HIV-1 transmission within this population.

[Effects of Human Immunodeficiency Virus-positive Mothers Receiving Antiretroviral Therapy to Prevent Mother-to-child Transmission on the Growth and Development of 18-month-old Children in Lingshan County of Guangxi].

Objective To evaluate the effects of antiretroviral therapy(ART)for the prevention of mother-to-child transmission(PMTCT)of acquired immune deficiency syndrome(AIDS)on the growth and development of 18-month-old children born by human immunodeficiency virus(HIV)-positive pregnant women in Lingshan County,Guangxi Zhuang Autonomous Region,and provide scientific evidence for improving the ART medication plan for PMTCT.Methods Lingshan County,ranking the first in the HIV-epidemic counties of Guangxi,was selected as the research site.According to the design of retrospective case-control study,we assigned all the subjects into the case group and the control group:(1)The case group included the HIV-positive pregnant women who had received ART for PMTCT and their HIV-negative infants in Lingshan County from 2010 to 2017.The historical cards and PMTCT data of them were collected from the national PMTCT database.(2)The control group included the healthy pregnant women and their healthy babies born in the Lingshan Maternity and Infant Hospital in 2017,and the children's growth and development data were collected.The stunted growth in children was defined as at least one of the three main indicators of body height,body weight,and head circumference below the normal range.Results The number of HIV-positive mothers and their infants in the case group was 391 and 368,respectively,and 87.21%(341/391)and 95.38%(351/368)of mothers and infants respectively received ART medication.The HIV positive rate,mortality rate,and mother-to-child transmission rate of 18-month-old children were 1.36%(5/368),4.35%(16/368),and 2.01%(5/249),respectively.The incidence of stunted growth of 18-month-old children in the case group and the control group was 42.12%(155/368)and 23.06%(101/438),respectively,with significant difference(χ2=33.520,P<0.001).Conclusion After HIV-positive mothers in Lingshan County of Guangxi received ART for PMTCT,the incidence of growth stunting in 18-month-old children increased.

Small molecule STAT3 inhibitor, 6Br-6a suppresses breast cancer growth in vitro and in vivo.

Signal transducer and activator of transcription 3 (STAT3) protein frequently overexpressed in many malignancies and plays an essential role in regulating proliferation, apoptosis, migration and invasion in cancer cells. However, No STAT3 inhibitor was used clinically. In this study, we evaluated the toxic potential of a novel STAT3 inhibitor, 6Br-6a in breast cancer cell lines. The anti-cancer effect and underlying mechanism of 6Br-6a on MDA-MB-231 and MCF-7 cells were determined in vitro and in xenograft mouse model. Our data demonstrated that 6Br-6a significantly induced cell cycle arrest and cell apoptosis in breast cancer via blocking the activation of STAT3. Finally, we verified these inhibitory effects of 6Br-6a in the MDA-MB-231 xenograft mouse model. In conclusion, 6Br-6a effectively inhibited activation of STAT3 and induced cell cycle arrest and apoptosis via regulating cyclin D1 and Bcl-2 expression. All of these data indicate that 6Br-6a could be a potential candidate for the treatment of breast cancer.

Testing and linkage to HIV care in China: a cluster-randomised trial.

BACKGROUND: Multistage, stepwise HIV testing and treatment procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete engagement of patients along the care cascade translates into high preventable mortality. We aimed to identify whether a structural intervention to streamline testing and linkage to HIV health care would improve testing completeness, ART initiation, and viral suppression and reduce mortality. METHODS: We did a cluster-randomised, controlled trial in 12 hospitals in Guangxi, China. All hospitals were required to be level 2A county general hospitals and ART delivery sites. We selected the 12 most similar hospitals in terms of structural characteristics, past patient caseloads, and testing procedures. Hospitals were randomly assigned (1:1) to either the One4All intervention or standard of care. Hospitals were randomised in a block design and stratified by the historical rate of testing completeness of the individual hospital during the first 6 months of 2013. We enrolled patients aged 18 years or older who were identified as HIV-reactive during screening in study hospitals, who sought inpatient or outpatient care in a study hospital, and who resided in the study catchment area. The One4All strategy incorporated rapid, point-of-care HIV screening and CD4 counts, and in-parallel viral load testing, to promote fast and complete diagnosis and staging and provide immediate ART to eligible patients. Participants in control hospitals received standard care services. All enrolled patients were assessed for the primary outcome, which was testing completeness within 30 days, defined as completion of three required tests and their post-test counselling. Safety assessments were hospital admissions for the first 90 days and deaths up to 12 months after enrolment. This trial is registered with ClinicalTrials.gov, number NCT02084316. FINDINGS: Between Feb 24 and Nov 25, 2014, we enrolled 478 patients (232 in One4All, 246 in standard of care). In the One4All group, 177 (76%) of 232 achieved testing completeness within 30 days versus 63 (26%) of 246 in the standard-of-care group (odds ratio 19·94, 95% CI 3·86-103·04, p=0·0004). Although no difference was observed between study groups in the number of hospital admissions at 90 days, by 12 months there were 65 deaths (28%) in the in the One4All group compared with 115 (47%) in the standard-of-care group (Cox proportional hazard ratio 0·44, 0·19-1·01, p=0·0531). INTERPRETATION: Our study provides strong evidence for the benefits of a patient-centred approach to streamlined HIV testing and treatment that could help China change the trajectory of its HIV epidemic, and help to achieve the goal of an end to AIDS. FUNDING: US National Institute on Drug Abuse Clinical Trials Network and China's National Health and Family Planning Commission.

[Investigation of current cognition of occupational exposure to HIV in healthcare workers in Liuzhou, China].

OBJECTIVE: To investigate the current cognition of occupational exposure to human immunodeficiency virus (HIV) and the personal occupational protection awareness in healthcare workers in Liuzhou, China. METHODS: A total of 270 healthcare workers were selected from 10 hospitals in Liuzhou by stratified random sampling for a cross-sectional study. And a self-administered questionnaire of occupational exposure to HIV was designed to conduct a survey. The descriptive analysis of data was carried out by Excel. And a logistic regression analysis was done to analyze the effects of different factors on healthcare workers' cognition of occupational exposure to HIV using the statistical analysis software SPSS 19.0. RESULTS: A total of 260 usable questionnaires (96.3%) were returned. Among them, 220 healthcare workers (84.6%) had received the trainings on occupational exposure to HIV; 223 healthcare wofkers (85.8%) were aware of the rules and regulations on prevention of occupational exposure to HIV and the operation procedures in their hospitals. The healthcare workers who had not received the trainings or had not known the rules and regulations and the operation procedures were mainly from primary or secondary hospitals. A total of 106 healthcare workers (40.8%) had directly contacted patients' blood or body fluids; 154 healthcare workers (59.2%) were injured by sharp instruments, and most were hollow needle stick injuries (98/154, 63.6%). A total of 168 healthcare workers (68.08%) had better cognitive awareness of occupational exposure to HIV, and 76 healthcare workers (29.2%) had moderate cognitive awareness. Some healthcare workers had poor knowledge in the common sense of AIDS/HIV and occupational exposure to HIV, the personal protection awareness of occupational exposure, or the disposal measures after occupational exposure. The univariate analysis using chi-square test showed that occupation and professional title were significantly correlated with the cognition (P<0.05). The multivariate logistic regression analysis showed that the doctors (OR3.8; P<0.05), nurses (OR3.04, P<0.05), and laboratory technicians (OR=9.51, P<0.05) had better awareness compared with the others. The healthcare workers with a primary or lower professional title had poorer awareness compared with the healthcare workers with a higher professional title (OR=0.47, P<0.05). CONCLUSION: Healthcare workers have the risk of occupational exposure to HIT. They do not have comprehensive and systematic knowledge related to occupational exposure to HIV, and they have a high demand for training.

Simplified HIV Testing and Treatment in China: Analysis of Mortality Rates Before and After a Structural Intervention.

BACKGROUND: Multistage stepwise HIV testing and treatment initiation procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete patient engagement along the continuum of HIV care translates into high levels of preventable mortality. We aimed to evaluate the ability of a simplified test and treat structural intervention to reduce mortality. METHODS AND FINDINGS: In the "pre-intervention 2010" (from January 2010 to December 2010) and "pre-intervention 2011" (from January 2011 to December 2011) phases, patients who screened HIV-positive at health care facilities in Zhongshan and Pubei counties in Guangxi, China, followed the standard-of-care process. In the "post-intervention 2012" (from July 2012 to June 2013) and "post-intervention 2013" (from July 2013 to June 2014) phases, patients who screened HIV-positive at the same facilities were offered a simplified test and treat intervention, i.e., concurrent HIV confirmatory and CD4 testing and immediate initiation of ART, irrespective of CD4 count. Participants were followed for 6-18 mo until the end of their study phase period. Mortality rates in the pre-intervention and post-intervention phases were compared for all HIV cases and for treatment-eligible HIV cases. A total of 1,034 HIV-positive participants (281 and 339 in the two pre-intervention phases respectively, and 215 and 199 in the two post-intervention phases respectively) were enrolled. Following the structural intervention, receipt of baseline CD4 testing within 30 d of HIV confirmation increased from 67%/61% (pre-intervention 2010/pre-intervention 2011) to 98%/97% (post-intervention 2012/post-intervention 2013) (all p < 0.001 [i.e., for all comparisons between a pre- and post-intervention phase]), and the time from HIV confirmation to ART initiation decreased from 53 d (interquartile range [IQR] 27-141)/43 d (IQR 15-113) to 5 d (IQR 2-12)/5 d (IQR 2-13) (all p < 0.001). Initiation of ART increased from 27%/49% to 91%/89% among all cases (all p < 0.001) and from 39%/62% to 94%/90% among individuals with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). Mortality decreased from 27%/27% to 10%/10% for all cases (all p < 0.001) and from 40%/35% to 13%/13% for cases with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). The simplified test and treat intervention was significantly associated with decreased mortality rates compared to pre-intervention 2011 (adjusted hazard ratio [aHR] 0.385 [95% CI 0.239-0.620] and 0.380 [95% CI 0.233-0.618] for the two post-intervention phases, respectively, for all newly diagnosed HIV cases [both p < 0.001], and aHR 0.369 [95% CI 0.226-0.603] and 0.361 [95% CI 0.221-0.590] for newly diagnosed treatment-eligible HIV cases [both p < 0.001]). The unit cost of an additional patient receiving ART attributable to the intervention was US$83.80. The unit cost of a death prevented because of the intervention was US$234.52. CONCLUSIONS: Our results demonstrate that the simplified HIV test and treat intervention promoted successful engagement in care and was associated with a 62% reduction in mortality. Our findings support the implementation of integrated HIV testing and immediate access to ART irrespective of CD4 count, in order to optimize the impact of ART.

[Pathological observation of lung injury in experimental animals induced by non-ferrous metal (tin) dusts].

OBJECTIVE: To explore the characters of lung injury induced by tin dusts and to provide the diagnosis evidence of tin pneumoconiosis. METHODS: Forty SD rats were randomly divided into four groups: the group exposed to tin dusts from smelting workshop, the group exposed to tin dusts from tin refining workshop, the positive control group exposed to standard quartz dusts and the negative control group exposed to saline. The pathological changes of rat lungs were observed dynamically. RESULTS: In rats exposed to tin dusts, on the 30th day after exposure to tin dusts, the scattered hoar tip size of the spots in surface and section of the lungs were observed, the scattered focal granulomatous inflammation around the small bronchi and dust particles in lung tissue were observed under microscope; on the 90th day after exposure to tin dusts, the granulomatous inflammation increase, the fibroblasts proliferation, collagen fibers formation and positive VG staining were found. There were significant differences, as compared with positive or negative controls (P < 0.05). These pathological changes were basically the characters of specific pathological changes in early tin pneumoconiosis. CONCLUSION: Non-ferrous metal tin dusts can induce the specific lung injury (granuloma formation) in lung tissue of rats exposed to tin dusts, which fulfilled the diagnostic criteria of specific pathological changes in early tin pneumoconiosis.