The Research of Site Supervision of Aids Screening Laboratory in Sichuan Province During 2011-2020: A Laboratory Capacity-based Continuity Study

Background: Expanding the scale of Human immunodeciency virus (HIV) testing is long-term strategy for acquired immune deciency syndrome (AIDS) prevention and control. This study analyzes the capacity of HIV screening laboratory operation to nd inuencing factors and guarantee quality of test. The result could also provide reference value for management of AIDS laboratories in other provinces and even abroad. Methods: Randomly checking AIDS screening laboratories in 21 cities and counties (districts) every year and also lling out evaluation form of site supervision. Analyzing the inuence factors of HIV screening laboratory operation though Logistic regression. Result: From 2011 to 2020, there were 68, 75, 81, 82, 87, 80, 33, 57, 85 and 87 HIV screening laboratories conducted site supervision respectively, of which 60(88.24%), 74 (98.67%), 76 (93.83%), 81(98.78%), 60(68.97%), 51(63.75%), 23(69.70%), 41(71.93%), 59(69.41%) and 60(68.97%) had excellent results. It was found that the excellence rate of each institution was relatively stable during 2011-2014, while the overall score of each regional laboratory in 2015 uctuated signicantly than 2015 before and all of excellence rate has declined. Hospitals and centers for disease control and prevention (CDC) were with higher frequency of assessment. Multivariate logistic regression analysis found these following variables were signicant inuencing factors of laboratory quality, including stang, standard operating procedure (SOP) and management system, periodic calibration of equipment, standardization of HIV testing, uniqueness of sample number, standardized use of quality control materials, standard drawing of quality control chart, biosafety facilities . Conclusion: The overall operation of HIV screening laboratories in the whole province is good and the quality management can normatively meet the requirements, which also meet the demand of expanding HIV testing. It also has lots of questions inuencing laboratory quality, laboratory work well.


Background
Since the rst AIDS case was reported in Sichuan Province in 1992, the number of HIV infected persons and cases in Sichuan Province is increasing annually, Sichuan Province has become one of the main epidemic areas in China [1] . The incidence and mortality of HIV have increased from 10.12 per 100,000 and 2.00 per 100 000 in 2011 to 31.76 per 100 000 and 5.92 per 100 000 in 2019, respectively [2][3][4] . The improvement of HIV detection technology and diagnostic reagent quality at home and abroad has promoted the progress of HIV prevention and cure over recent years. China's 13th Five Year Action Plan for HIV/AIDS Containment and Prevention requires accomplishing three goals, which including more than 90% of infected people and patients who has been diagnosed and aware of their own psysical condition. HIV testing is the rst step in AIDS prevention and expanding the scale of testing is also a long-term strategy for AIDS prevention and control. However, the expansion of testing work is closely related to the continuous improvement of the laboratory network, the number of HIV testing sites, screening and certi cation laboratories in Sichuan Province has increased from 1194, 552 and 27 in 2011 to 4885, 753 and 74 in 2020, respectively, which covering the whole province included 183 districts and counties. As of 31 December 2020, Sichuan Province has 5712 AIDS test institutions and the number of testing reached 37.7 million, an increase of 855.38 %from 2011 (Fig. 1). The testing quality of HIV screening laboratories has a great impact on the case detection of HIV. With the increasing of testing institutions and expanded testing, the guarantee of testing quality is extremely important. In order to strengthen the management of HIV testing laboratories, improve the testing level, and instantly nd and solve the problems, Sichuan Provincial Center for Disease Control and Prevention has started the site supervision of HIV testing laboratories in the whole province since 2009 and Sichuan Province is also the rst province in China to start the site supervision of AIDS testing laboratories. This paper analyzes the result of site supervision of AIDS screening laboratories during 2011-2020, which may provide reference value for the management of AIDS laboratories in other provinces and even abroad. Methods 1.1Objective From 2011 to 2020, randomly checking AIDS screening laboratories in 21 cities and counties (districts) every year, which included local CDC, medical institutions, maternal and child care centre and other institutions.
1.2 Assessment method Organized by the HIV / AIDS con rmation center laboratory of Sichuan Center for Disease Control and Prevention. The panel members of HIV / AIDS con rmation laboratories in 21 cities were selected as members of the site supervision expert group, who will check and score on HIV / AIDS screening laboratories. The members of the expert group did not participate in the site supervision of the screening laboratories in their own workplace. 1.3The assessment indexes Taking the assessment indexes as the analysis variables, including the quali cation of experimenter, the normalization of materials' ling, SOP, management system, quality management of surveillance area, standardization of laboratory network information lling, equipment management, standardization of HIV screening report and retest test sheet, uniqueness of HIV sample number, the quality control,laboratory area and personal protective equipment, biosafety facilities, reagent use and management. Speci c scoring plan may refer to "Supervision Program of AIDS Testing Laboratory in Sichuan Province" issued by Sichuan Center for Disease Control and Prevention. 1.4 Score standard Total score ≥ 90 was de ned as excellent and total score < 90 was de ned as non-excellent. 1.5 Statistical analysis Using EXCEL to establish a database and carry out description and statistical analysis by SPSS 25.0 software, the variables were analyzed by single factor logistic regression analysis, which P < 0.2 for multivariate regression analysis and P < 0.05 was considered as statistically signi cant. The map in this gure is designed by using the ArcMap 10.6 software.
During 2011-2020, perform site supervision institution covered hospitals, CDC, maternal and child care center, blood donation and supply institutions and the judiciary. The proportion of site supervision in hospital and CDC had increased gradually, and institution with higher frequency of supervision was in hospitals and CDC. The speci c distribution is shown in Fig. 3. The average scores of 21 cities in the past 10 years were analyzed and it can be seen that there was no signi cant difference in the laboratory conditions of cities before 2015. But the overall scores of laboratories in all regions in 2015 were uctuated than 2015 before. And the scores of Chengdu, Zigong, Panzhihua, Nanchong, Aba and Ganzi have obvious uctuations (Table  1). Note: "/" the site supervision mode of 2017-2018 was a round involved two years.

The analysis of excellence rate of different institutions during 2011-2020
Through the analysis of the excellence rate of different types of assessment laboratories from 2011 to 2020, it was found that the excellence rate of each institution was relatively stable during 2011-2014, while the overall score of each regional laboratory in 2015 uctuated signi cantly than 2015 before and all of excellent rate has declined (Table 2).  Standardized use of quality control materials Note: *P value < 0.2, **P value < 0.05, ***P value < 0.001.
Item which without judgement: these were not required to site supervision in 2011 included uniqueness of HIV sample number, thermostatic facilities, laboratory area and personal protective equipment. Standardized use of quality control materials, batch inspection and batch inspection with reagents used were not required to site supervision during 2011-2012. Item both outer quality control and quality control of rapid diagnosis were not asked to site supervision in 2011-2013. Laboratory SOP and management and quality control and on-site evaluation of HIV testing sites in the jurisdiction were not required to site supervision before 2015. Item both Standardization of laboratory network information lling and review the correctness of HIV laboratory test data in the jurisdiction were not judged because Laboratory network information system was shut down during 2016-2019.

Discussion
Sichuan Provincial Center for Disease Control and Prevention organized and carried out site supervision of HIV screening laboratories in the past 10 years, which found the overall operation of HIV screening laboratories in the whole province is good and the quality management can normatively meet the requirements of Management Measures for National AIDS Testing and National AIDS Testing Standards ( 2009 and 2015 versions ) [7][8][9] . During 2011-2020, laboratory supervised covers 173 districts and counties included hospitals, CDC, blood donation and supply institutions, the judiciary and other institutions each year. The excellent rate before 2015 is more than 85%. With the revision and update of National AIDS testing technical speci cation, the requirements for laboratory testing and management are more rigorous and the de ciency of laboratories are also found. Which also resulted in the overall excellent rate of laboratories in 2015 was decreased, such as Chengdu, Zigong, Panzhihua, Nanchong, Aba, Ganzi. After continuous recti cation in recent years, the excellent rate has also begun to improve every year.
This analysis found that the actual operators are quali ed was an important factor affecting the quality of HIV screening laboratories. A total of 469 times of site supervision laboratory had sample testing problems included HIV screening and testing original records are not standardized, such as over altered, the original records and double test records are inconsistent, the experiment did not correspond with the reagent instructions and standard process, and did not add negative and positive control according to the kit instructions. It is suggested that each laboratory should strictly follow the reagent instructions, standardize the record lling, and reduce the frequency of modi cation. Similarly, some laboratories also have some problem, included did not have the uniform rules of sample number and not established database, no timely backup and place document on le, did not establish security measure. The above problems are also crucial to affect the experiment results. Therefore, laboratories should formulate uni ed numbering rules from sampling to detection, update the database in time and take con dentiality measures. In addition, both outer quality control and standard drawing of quality control chart are the vital factors affecting the normal operation of laboratories. The main problems included the quality control chart was not normative, not analyzed and corrected timely when it out of control. some laboratories did not do external quality control during rapid testing or only do positive quality control [10] . Laboratories could set up position which is specially responsible for the quality control chart. Meanwhile, Laboratories also should formulate the quality control rules are t for own laboratory, clarify the solutions when quality control chart changed and out-of-control, strengthen the learning of quality control and regularly conduct quality control analysis seminars and assessment [11] . There are still some problems in the integrity and management of SOP documents, such as incomplete and untimely update of SOP and some laboratories even existed direct errors in SOP. Each laboratory should establish and update the SOP rules suitable for the laboratory to standardize the operation and management of the laboratory, make it easy to the experimenter follow the rules. Moreover, we could strengthen assessment effort of the sample and implement the disquali cation mechanism of laboratories in the future work [12] .
Secondly, AIDS laboratory sta ng is one of the important factors to ensure the quality of testing, and the rate of institutional excellence with su cient sta ng is 3.12 times than poor sta ng. Thus, AIDS laboratory should be equipped with personnel to ensure the normal and orderly operation of the experiment. We also found that the biosafety awareness of laboratory personnel was still inadequate, such as no eye washing device, non-standard of biological waste treatment and incomplete records. Some laboratory disinfectants did not match the requirements of Technical speci cation for disinfection of medical institutions (2012 version) [13] and even not used biological waste bags, others used sharps and glassware. Besides the need of increasing the laboratory sta ng, regular and learning should be carried out. Furthermore, it could set further study spot by the local municipal CDC to evaluate regular work of experimenters [14] . While improving the testing technology level of AIDS screening laboratories, we should also strengthen the biosafety awareness and reduce the occurrence of occupational exposure accidents [15] . When an accident occurs, it shall be strictly enforced in accordance with the requirements of Pocedures for occupational exposure to HIV infection [16] .
Finally, the normal operation of the equipment is of great signi cance to prerequisite for the quality assurance of experiment. The calibration of equipment was not in time may affect the accuracy of sample testing, such as the sampling error of pipettors, the systematic error caused by the inaccurate reading of the ELISA, the inaccurate measurement of the thermometer could result in reduction of quality of sample and reagent, inaccurate pressure of autoclave pressure gauge leads to incomplete sterilization and even biosafety hidden danger. It is suggested that worked out the plan of maintenance and calibration of each equipment and completed the archive les. The calibration of equipment should carry out and record on time [17] .
At present, AIDS publicity and education is not limited to its prevention, diagnosis and therapy, but also includes HIV testing. Now, colleges and universities have build HIV testing methods and testing processes into the curriculum and the government has incorporated the construction of laboratories into the annual check, so particular emphasis is placed on the laboratory testing. Through the site-assessment of HIV screening laboratories in Sichuan Province from 2011 to 2020, it can be seen that many factors such as sta ng, quality of instruments and equipment, testing process, quality control and biosafety determine the normal operation of the laboratory. In recent year, the detection ability of most laboratories is gradually improved and management mode is steadily standardized, but each part is still strictly required to ensure operation of the laboratory work well. This survey also proved the necessity of site supervision, which can timely nd, solve and reduce the possible risks in the operation of the laboratory and guarantee the accuracy of the test results. Each laboratory should strengthen technical training and guidance step by step. This paper also provides new ideas for the management mode of HIV laboratories in other provinces and even abroad.
This paper also has limitation. Firstly, this site supervision does not cover 100% of the districts and counties and the problem may be found insu ciently. Secondly, because of the revision of National AIDS testing technical speci cation and the adjustment of strategies for AIDS prevention and control, some indicators in the site supervision are accordingly changed, which may affect the comparability of results per year. Finally, the differences of both personal competence and understanding of various norms made this result is a certain subjectivity.

Conclusions
This study describes and analyzes operation quality of HIV screening laboratory in Sichuan, which nds in uencing factors to ensure quality of testing. It also demonstrates the importance of site supervision. We suggest HIV screening laboratories should follow strictly HIV testing procedure and manage normatively. This paper also provides new ideas for the management mode of HIV laboratories in other provinces and even abroad.