Trends Of Transmission Route,ART Regimen And Timing Of HIV/AIDS Patients In Guangzhou From 2004 To 2019,and Multivariate Failure Time Survival Analysis

Objectives:Acquired immunodeficiency syndrome(AIDS)caused by human immunodeficiency virus(HIV)infection is a serious global public health and social problem.Since the advent of highly active antiretroviral therapy(ART),benefiting from the progress of the times and the implementation of the national free antiretroviral therapy policy(NFA TP),more and more HIV/AIDS patients have received ART,and their life has been evidently prolonged.At the same time,the transmission routes,ART regimens and timing of the patients have also changed significantly.In this study,we intended to use the database of free antiretroviral treatment for AIDS in Guangzhou’s largest infectious diseases hospital from 2004 to 2019 to establish a retrospective cohort,describe the trendline of patients’ transmission routes,ART regimens and timing year by year.Futhermore,we are going to explore the impact of different transmission routes,ART regimens and timing on patients’ multiple outcomes,so as to understand the differences of patients’ prognosis with different transmission routes,analyze the differences of efficacy and safety among different ART regimens,and determine the risks that should be controlled while generalizing the "immediate initiation" strategy.This study can help the AIDS prevention and control institutions at all levels in Guangzhou to fully understand the characteristics and trend of change of the patient population in this city,and further carry out more efficient diagnosis and treatment according to the differences of comprehensive prognosis of people with different characteristics,and provide valuable reference for the adjustment of NFATP.Methods:In this study,a retrospective cohort was conducted to collect the baseline and follow-up data of 17,741 HIV/AIDS patients who newly received ART from 2004 to 2019 in Guangzhou’s largest infectious disease hospital.Firstly,the frequency tables are used to describe the distribution of patients’ baseline demography,diagnosis,transmission route,ART regimen and timing,and the percentage bar charts are used to describe the trend of patients’ transmission routes,ART regimens and timing year by year.Secondly,Kaplan-Meier and Log-rank test were used to compare the survival curve of six outcomes(including death,virological failure,lost to follow-up,drug resistance,drug-induced hepatotoxicity and drug-induced renaltoxicity)of different transmission routes,ART regimens and timing.The incidence density of each outcome of patients in each group was calculated.Cox marginal effect models are constructed to analyze the multiple outcomes,and the sandwich variance robust estimation is used to correct the influence of correlation among multiple outcomes on parameter estimation.Univariate analyses are performed for calculating the crude risk ratio(c HR)adjusted risk.The covariates with statistically significant influence on the multiple outcomes are selected for multivariate analysis,and adjusted risk ratio(a HR)of each outcome will be calculate.Subgroup analyses are conducted to figure out the influence of different ART regimens and timing on patients in the sub-population of homosexual and heterosexual transmission.Finally,sensitivity analysis is used to compare the results of Cox marginal effect model with those of classical Cox regression model,and to confirm the stability of multivariate failure time results.Results:1.A total of 16,946 HIV/AIDS patients were included in the study,with a total follow-up of 59,050.48 person-years.2.From 2004 to 2019,the proportion of intravenous drug users or blood transfusion infections in Guangzhou decreased year by year,and in recent years,it has approached to zero.Sexual transmission has become the route of most patients,among which the proportion of homosexual sexually transmitted infections is increasing rapidly year by year.From2004 to 2011,the main ART regimens used by patients in Guangzhou were D4T(DDI)+3TC+EFV(NVP/RPV/RAL)and TDF(AZT/ABC)+3TC+NVP(RPV),but after 2012,it decreased sharply,and TDF+3TC+EFV quickly became the most widely used ART scheme for patients.After2016,the amount of TDF(AZT/ABC)+3TC+DTG(RAL)and compound regimens users showed a slow increasing trend,but TDF+3TC+EFV was still the ART regimens chosen by most patients.From 2004 to 2019,the ART timing of patients in Guangzhou showed a trend of advancing year by year.The ratio of late initiation group decreased,while that of early initiation group increased.3.For patients with different transmission routes,when compared to homosexual transmission infection,patients infected with HIV through heterosexual transmission have a higher risk of death,lost to follow-up and drug-induced hepatotoxicity;patients infected with HIV through intravenous drug use or blood transfusion have a higher risk of death,virological failure,lost to follow-up,drug-induced hepatotoxicity and drug-induced renal toxicity;patients infected with HIV through other routes have a higher risk of death,lost to follow-up,drug resistance,drug-induced hepatotoxicity and drug-induced renaltoxicity.For patients with different ART regimens,when compared to TDF+3TC+EFV,patients who use TDF(AZT/ABC)+3TC+NVP(RPV)have higher risk of death,drug-induced hepatotoxicity and drug-induced renaltoxicity;the patients who use TDF(AZT/ABC)+3TC+LPV/r have a higher risk of death,lost to follow-up and drug-induced renaltoxicity.Patients who use TDF(AZT/ABC)+3TC+DTG(RAL)have a higher risk of death,lost to follow-up and drug-induced renaltoxicity.The patients who use D4T(DDI)+3TC+EFV(NVP/RPV/RAL)have a higher risk of death,drug-induced hepatotoxicity and drug-induced renaltoxicity,but a lower risk of treatment detachment and drug resistance.For patients with different ART timing,when compare to late initiation group,the risk of virological failure and drug resistance in the early initiation group,standard treatment,group mid-term initiation group is lower,while the risk of lost to follow-up is higher.Conclusions:1.Sexual transmission is the infection route of the most HIV/AIDS patients in Guangzhou,in which the proportion of homosexual transmitted infections is increasing year by year;TDF+3TC+EFV is the most frequently used ART regimens for patients in Guangzhou.In recent years,the number of users of NRTIs+ INSTI and compound regimens is increasing.The timing for patients to accept ART in Guangzhou is constantly earlier.The ratio of patients in the late initiation group decreased significantly,and the baseline immune status increased,but the overall level is still at a low level.2.Among the patients in Guangzhou,the risk of death,lost to follow-up and drug-induced hepatotoxicity and renaltoxicity of homosexuals is lower than that of those infected by other routes,and it is the population with the best comprehensive prognosis.TDF+3TC+EFV users have lower risk of death and kidney injury than other users of treatment,and it is the ART regimen with the best efficacy and safety among patients in Guangzhou.Early initiation of ART significantly reduced the risk of death,virological failure and drug resistance of patients in Guangzhou,but also increased the risk of lost to follow-up.3.Sexually transmitted infections are the key groups of HIV/AIDS prevention and control in Guangzhou,among which men who have sex with men(MSM)is the most important.AIDS prevention and control institutions at all levels should strengthen the education for the above groups,promote patients to accept ART as soon as possible after infection,and keep good compliance to avoid leaving the follow-up.In the choice of ART regimen,TDF+3TC+EFV should be the first choice as the combination of therapeutic drugs for patients,or NRTIs+INSTI or the compound regimen can be selected according to the characteristics of patients,so as to bring the greatest therapeutic benefits to patients,so as to delay the disease progression and improve the quality of life.