Analysis on the associated factors of drop-out from HIV antiviral treatment in Kunming City

Background: With the implementation of national anti-viral and expanded treatment policies, the number of HIV-infected people receiving anti-viral treatment is increasing, and the number of people drop out of ART is also increasing year by year in Kunming. Thus,the aim of this study was to investigate the causes and influencing factors of drop out in treatment of HIV infection in Kunming and to explore the countermeasures to reduce the rate of drop out. Methods: Using convenient sampling method, the HIV infected people found in Kunming as of August 31, 2018 were selected.187 patients who had received antiviral treatment were treated as the treatment group, and 252 patients who had received antiviral treatment but drop out were treated as the drop out group. Results: Multivariate analysis shows that geographical division, monthly income, whether or not to receive minimum living allowance, and referral methods of follow-up institutions are the factors that affect the drop out of antiviral treatment of HIV infected persons. Conclusion: To increase the attention of vulnerable patients in ART, patients with adverse reactions to treatment drugs should be treated or replaced in a timely manner, and AIDS-related medical services and government support should be strengthened in order to reduce the rate of drop out.

completely treatment success are the common goals of the country, health-care workers and HIV infected patients [3]. In 2015, UNAIDS is embarking on a fast-track strategy to end the AIDS epidemic by 2030 [4]. Since the implementation of the national free anti-viral treatment and expanding treatment policies, the number of HIV infected people receiving ART is increasing [5,6], the number of people dropping out of ART is also increasing year by year [6,7]. Controlling the dropout rate of antiretroviral therapy can effectively reduce the mortality rate of AIDS, contribute to the implementation of the fast track strategy and to realize of the three 90% goals.This article analyzes the reasons and influencing factors of HIV-infected people dropping out of antiretroviral therapy in Kunming city, and explores the methods to reduce the rate of drop out.

Study setting, design, and population
The epidemic situation database and antiretroviral therapy database were derived from the National AIDS Integrated Prevention and Control Information System, deadline is August 31, 2018.
HIV-infected people receiving antiretroviral therapy in the database were selected as the treatment group, those who had received antiretroviral therapy but are currently drop out as the drop out group.
The types of drop out in this study includes drop out of follow-up and stop taking ART medicine.
HIV-infections from 14 counties of Kunming City were selected to participate in the survey.
Kunming Center for Disease Control and Prevention were designed and conducted a questionnaire survey.Conducted a pre-inverstigation of qualitative interviews to control bias in the design stage of the project, then further revised and improved the questionnaire. After the questionnaire was formulated, the reliability of the questionnaire was assessed by retest method, and the consistency rate of the questionnaire was 0.86. Experts were asked to test the content and structure validity of questionnaire, experts believed the validity was good. According to the definition, inclusion and exclusion criteria to selected the subjects to control the selection bias.A questionnaire survey is conducted by trained investigators to make one-to-one interviews in order to control information bias.The contents of the questionnaire include demo graphical, services related to HIV treatment, etc.
In this study, strictly quality control was carried out in different stages of project design, data collection and data analysis.

Definitions
Drop out of follow-up refers to after the appointed follow-up period more than 90 days, the patients do not actively contact the follow-up doctors or doctors could not contact the patient, and did not know the reasons for the discontinuation of treatment. Discontinuation refers to patients discontinuation of treatment for toxic side effects or various reasons, even doctors can contact patients, but patients no longer want to receive treatment [8].

Inclusion and exclusion criteria
Inclusion criteria for the drop out group were: (1) age 18-75; (2) those who dropped out of follow-up or stopped taking ART medicine after treatment; (3) those who cooperated with the investigators with informed consent; (4) those who without major diseases or mental disorders.
Exclusion criteria in the treatment group were: (1) age 18-75; (2) adherence to treatment after initiating antiretroviral therapy; (3) those who cooperated with the investigators with informed consent; (4) those who without major diseases or mental disorders.

Statistical analysis
When the questionnaire data were entered, verification documents were set to reduce the input errors. Double data entry consistency checks were carried out to detect and correct the input errors in time. Stata version 11.0 software was used for statistical data analysis. Univariate analysis was performed by Chi-square test, P value 0.05 was considered statistically significant.Meaningful factors in single-factor analysis were incorporated into multi-factor analysis. Logistic regression was used to analyze the influencing factors of the drop out of antiretroviral therapy.
The level of significance was defined at P < 0.05.

Results
A total of 439 valid questionnaires were collected, of which 252 were in the drop out group and Single factor analysis of antiretroviral therapy services Through the single factor analysis of anti-virus treatment services provided by HIV/AIDS prevention and control institutions, it was found that referral methods provided by follow-up institutions and ART information provided by follow-up institutions were the influencing factors of dropping out of treatment (P < 0.05).

Reasons for drop out of antiretroviral therapy in HIV-infected patients
The top three reasons for the drop out of antiretroviral therapy in HIV-infected patients were: serious side effects; need to persist in taking medicine regularly; Medication interruption due to imprisonment. Medication interruption due to imprisonment 67 Treatment information is asynchronous due to the change of current address 60 No need to continue taking medicine for better health 39 Consider that the treatment is ineffective 25 Family members do not support treating 14

Discussion
Since China implemented the policy of four frees and one care, the drop out of ART has been an important issue affecting the therapeutic effect [9]. Drop out or not is an important index to measure the patient's treatment status and the success of treatment. Studies have shown that young, male, single or divorced [10], illiterate [11], the proportion of dropping out of treatment is higher. This study did not show that men were more likely to drop out. The higher the level of education is, the more difficult it is to drop out, which was consistent with the results of Mison Dahhab et al [12].
This study found that intravenous drug users were more prone to drop out, which was consistent with previous studies on the impact of injecting drug use on drop out [13]. Drug addicts are often managed by different institutions and departments, such as detoxification centers, prisons, methadone clinics, community antiretroviral therapy services institutions and so on. Job coherence among institutions should be strengthened to ensure that patients can receive sustained care and antiretroviral therapy in all institutions.
Multivariate analysis shows that regional division is the factor influencing the drop out of ART.
The HIV patients who come from rural areas was more easily to drop out of ART than that in urban areas. On the one hand, because of the concentration of antiretroviral therapy institutions in cities or towns, the availability of antiretroviral drugs for HIV-infected patients in rural areas was not high due to long journeys or transportation costs. Foreign studies also showed that too long distance to get drugs in hospitals was one of the factors affecting the maintenance treatment of patients [14]. This study includes a survey of antiretroviral therapy related medical services in the questionnaire. It is found that the mode of referral provided by follow-up agencies is an important factor affecting the drop out of antiretroviral therapy. Accompanied referral can greatly reduce the drop out rate of antiretroviral therapy, which is rarely mentioned in other studies. By establishing a bridge between follow-up agencies and antiretroviral therapy points, the time from receiving their HIV diagnosis to timely treatment can be significantly shortened, the treatments of HIV-infected patients can be promoted, and the drop out of ART can be reduced [15]. It is suggested that further study should be conducted on the role of accompany referral in reducing the drop out rate.
This study found that HIV-infected patients believed that the main reason for the drop out was drug side effects. 34.5% of HIV-infected patients drop out of ART because drug side effects, which was consistent with the results of other domestic studies [16,17]. Therefore, health workers are required to carry out effective compliance education before antiretroviral therapy, increase the number of early follow-up visits. Once adverse drug reactions were found, psychological counseling should be given to the patients in time. And serious adverse drug reactions should be deal with in time, treatment plans should be adjusted as appropriate.

Limitations
Our study has some limitations. Firstly, due to the cross-sectional study with small sample size.
And all the influencing factors are not included in the analysis, such as whether there are opportunistic infections before treatment, virological failure and other factors, which may cause bias.
Therefore, it is necessary to track the drop out of treatment of HIV-infected patients in the future's study.

Conclusion
This study indicated that we should strengthen the treatment and education for HIV-infected patients who is injecting drug use, low educational level or low economic level. Strengthen intervention measures, give financial supports and care assistance services.Strengthen AIDS-related medical services and government supports, so as to effectively improve the treatment retention rate and reduce the drop out rate of ART.

Declarations
Abbreviations ART: Antiretroviral therapy;UNAIDS:United Nations Programme on HIV/AIDS;HIV: Human