Shift in New HIV/AIDS Epidemic and Factors Associated with False Positives for HIV Testing: A Retrospective Study from 2013 to 2018 in Xi’an, China

Objectives: In the study, rstly, the epidemic characteristics of new HIV/AIDS were investigated in order to provide evidence for the targeted interventions; Secondly, the major factors of false positives (FP) for HIV testing were also determined. Methods: A retrospective review was performed in a teaching hospital in Xi’an between 2013 and 2018. The overall characteristics and epidemiological trends of new HIV/AIDS were described. Moreover, the distributions of FP cases in the gender, age and department were analysed, and the major factors of FP were determined by the Pareto analysis. Results: During the study, a total of 469 new HIV/AIDS were diagnosed, with an increasing prevalence from 0.0626% in 2013 to 0.0827% in 2018. Of them, the majority occurred in the Hans (99.57%), males (88.50%), people aged 21-50 years (76.97%), migrants (60.98%) and sexual contact route (88.70%). A rapid increase in the annual number of new HIV/AIDS and multiple routes of HIV transmission were found. The epidemic showed increasing trends in groups of young individuals, students and homosexual mode, however, a downward trend in the percentage of injecting drug use was also observed. 67.81% of FP cases were over 50 years old. The departments of oncology, obstetrics, hepatobiliary surgery, nephrology, cardiology and infectious disease were major factors of FP by Pareto analysis. Conclusions: The HIV/AIDS epidemic in Xi’an is still evolving, therefore, effective strategies, appropriate education and scaling up HIV testing should be developed to control the spread of the epidemic. In addition, old adults and specic departments were associated with FP.


Background
Since the rst AIDS case was identi ed in 1985 in Beijing, the HIV/AIDS epidemic had reached all 31 provinces/autonomous regions/municipalities in China in 1998. [1][2][3] In China, the national prevalence is still low (less than 0.1%), 4,5 however, the epidemic varies geographically, and the newly HIV infections and AIDS cases increase annually. [6][7][8] By the end of september 2018, there were 849,602 people living with HIV (PLWH) in mainland China. 9 The epidemic is severe in some midwest provinces (Sichuan, Chongqing, Guizhou, Hunan, Henan) and border communities (Xinjiang, Guangxi, Guandong), with annual new HIV/AIDS cases more than 5000. 10 The rst HIV infection was reported in Shaanxi in 1994. 11 From then on, acceleration in the incidence of HIV/AIDS is evident. Comparing with 2004, Shaanxi had the top three highest relative increase in the incidence of HIV infection (Relative change: 1.40) and high relative increase in the incidence of AIDS ( Relative change: 1.43) in China in 2014. 12 The annual new HIV/AIDS cases were more than 1000 since 2015. 13 Up to present, the resident population of Xi'an city is more than 10 millions and accounts for nearly one third of the total population of Shaanxi Province.

Overall characteristics of HIV testing
During the study period, a total of 622,139 subjects were included, with a male/female ratio of 1.003 and a median age of 50 years (Rang: 9 days to 96 years). Among them, 469 new HIV/AIDS cases were diagnosed. With a sharp growth in the testing subjects, the number of newly diagnosed cases and prevalence rate for HIV/AIDS have shown an increasing trend every year. Since 2015, the 4 thgeneration assay has been the predominant method for HIV screening, which resulted in a drastic increasing in the false-positive ratio (FPR). In addition, among the reactive cases for HIV screening, the not-diagnosed ratio (NDR) of the subjects who were lost to follow-up or less than 18 months age remained relatively stable (Rang: 9.09% to 15.0%),

Features of false positives (FP)
Of the 292 false positives from 2013 to 2018, 55.82% were male and 44.18% were female with a median age of 51 years (range: 16-86 years). In terms of age-speci c distribution, 11.3%, 10.96%, 9.83% and 67.81% were at 30, 31-40, 41-50 and 51 years old, respectively. The Pareto analysis showed that 5.14%-27.74% were from the department of oncology, obstetrics, hepatobiliary surgery, nephrology, cardiology, infectious disease and rheumatology with a cumulative ratio of 83.56%, which can be categorized as class A (major factors) associated with FP,

Discussion
The research data was from 622,139 subjects in Xi'an, and the MAIN FINDINGS OF THIS STUDY WERE: (1) The new HIV/AIDS cases and constituent ratios of students and young people increased yearly, however, the HIV prevalence remained still low; (2) Most of the HIV infections occurred in the Hans, males, young and middle-aged populations and migrants; meanwhile, the HIV/AIDS epidemic had spread across Shaanxi. The local infections were concentrated in Changan, Yanta and Beilin districts, however, most the infections of other areas in Shaanxi province were from Xianyang, Weinan and Ankang cities; (3) Multiple routes of HIV transmission were co-existent, in which the sexual contact was predominant and IDU route had decreased, however, the blood and vertical transmission were rarely observed; (4) The old adults and speci c departments , i.e., oncology, obstetrics, hepatobiliary surgery, nephrology, cardiology and infectious disease, were associated with FP.
Xi'an is not only a famous tourist city, but also an important central city in Western China. In addition, more than 30 universities with nearly a million students are located here. The large numbers of migrant workers, tourists, students play a "bridge"for the HIV/AIDS transmitting. 14 With the implementation of testing-based prevention for infectious diseases (HIV, HBV, HCV and Syphilis) for pregnant women, 15 before operation, interventional examination or treatment, the testing and con rmed cases for HIV increase yearly in China. 12,16 In addition, substantial intervention initiatives, such as "Four Free One Care" 17 and "prevention of mother-to-child transmission (PMTCT) programme", 18 have been introduced since 2003. which result in an obvious decrease in the proportion of HIV cases attributed to vertical transmission in China. 19 A rapid increase in the testing number and low constituent ratio of mother-tochild transmission for HIV/AIDS were also observed in the study.
China's HIV/AIDS epidemic began in the 1990s among injecting heroin users and commercial plasma donors. 20 Quite a few control policies, i.e., "law against drug use", 21 "voluntary and compulsory detoxi cation", 22 "methadone maintenance treatment (MMT) program", 23 and "commercial blood/plasma collection stations shut down and blood donors must be tested for HIV since 1995", 24 HAVE BEEN MADE AND PERFORMED EFFECTIVELY IN CHINA, which lead to the ratios of both IDU and blood routes among new infections decrease yearly. 5, 25 Simultaneously, there is a remarkable rise in both commercial sexual work at entertainment and extramarital sex via social apps in recent years. Thus, unsafe sexual behaviors have been the major cause of HIV infection in China. 26 In the study, the sexual contact was the most prominent route of HIV transmission in Xi'an, accounting for 88.6% of the cases, which was similar to other studies in China. [3][4][5] Recently, it is notable that the HIV/AIDS epidemic in adolescents/students and older adults is signi cant increase in China. 3,5,27 However, they are not usually considered as the high-risk population and are less likely to be tested for HIV. During the study period, the proportion of students among HIV cases increased yearly. In addition, the constituent ratios of HIV cases that were attributed to the students,-20 and 51-years age groups were 13.36%, 6.24% and 16.7%, respectively. Therefore, scaling up HIV prevention education and testing should be covered in both the high-risk population and the general population.
Another emerging theme in China is that a large number of PLWH are unaware of their infection status. 28,29 Owing to be in poor economic condition, fear of privacy being leaked and being STIGMATIZED , many high-risk people do not visit the hospital for HIV testing, which results in a high percentage of PLWH that can not been diagnosed. In the study, heterosexuality was the dominant transmission route (63.92%) , however, the proportion of HIV cases attributed to female was only 14.48%. Meanwhile, the notdiagnosed ratio of the reactive cases for screening test uctuated between 9.09% and 14.92%.
In China, people are sensitive to the HIV/AIDS topics, thus, more attention should also be paid to false positives (FP) for HIV screening test. In the study, 47.69% of FP cases were over 60 years of age. By department distribution, the oncology, obstetrics, hepatobiliary surgery, nephrology, cardiology, infectious disease and rheumatology were major factors associated with FP, with a cumulative ratio of 83.56%.

Conclusions
In Xi'an city, the HIV/AIDS prevalence is still low, and dramatic reductions in the HIV infections via IDU, blood and vertical transmission have also been achieved. However, the annual number of new HIV infections has increased rapidly. The targeted interventions for HIV/AIDS epidemic in Xi'an should be implemented as followings: First, the awareness of transmission routes, prevention for HIV infection should be strengthened further among the public to increase the using of condoms; Second, the HIV epidemic in migrants, adolescents/students and older individuals should be more concerned, and scaling up HIV testing should be covered in both the high-risk population and the general population to improve the diagnostic rate of HIV infection and reduc the risk for further transmission.

Years
Testing cases   The department distributions of the false-positive cases