| Background:Men who have sex with men（MSM）is the key population of HIV/AIDS prevention and control in China.Pre exposure prophylaxis（PrEP）,as a new global evidence-based biological intervention strategy,can effectively reduce the risk of HIV infection among HIV negative MSM by taking single or compound antiretroviral drugs.Currently,there are two ways of taking PrEP（daily and on-demand medication）.Daily medication needs to take one tablet of PrEP medicine every day,while on-demand medication needs to take PrEP medicine with"2-1-1"scheme at specific time points before and after the sexual behaviors.Previous large-scale clinical trials and real-world studies have shown that the efficacy of PrEP on preventing HIV infection relies on the medication adherence of PrEP users.PrEP could reduced the risk of new HIV infection by more than90%when MSM insist on taking TDF/FTC.The efficacy of PrEP decreased with the medication adherence reduced.When the medication adherence of PrEP was less than 40%,it was observed that there was no protective effect of preventing HIV infection.Therefore,it is necessary to timely monitor the PrEP medication adherence and identify the obstacles affecting the medication,with targeted intervention measures on PrEP medication adherence.There is no"gold standard"to evaluate the PrEP medication adherence in a quick,accuracy,and simple way.The new intelligent electronic drug monitoring device can collect the remote real-time data of PrEP medication adherence then provide with targeted intervention for non-compliance individuals.These real-world PrEP medication adherences will benefit the development of PrEP policy and guideline in China.Objective:To understand the willingness and influencing factors of using the intelligent electronic drug monitors among MSM via a cross-sectional survey.With a prospective cohort study to assess the consistence of PrEP medication adherence monitored by intelligent electronic drug monitors,self-report,pill count,and blood drug concentration.Conduct a RCT study to clarify the effect of intelligent electronic drug monitors with just-in-time monitoring and accurate intervention on PrEP medication adherence.Methods:From September to December 2019,we recruited participants to join the intelligent electronic drug monitoring study from PrEP users of CROPrEP in four clinics.The promotion from community opinion leaders and peers were the main strategies for recruitment.The inclusion criteria of eligible subjects included that they were male at birth and had anal sex;between 18-65 years old;subjects who reported one or more of the following risks within 6 months（unprotected insertional anal sex with male sexual partners,more than 2 male sexual partners,reported infectious sexually transmitted diseases,had a history of post exposure preventive medication,but did not receive post exposure preventive medication in recent 1 month）;the fourth generation HIV test is not reactive and HIV-1 RNA could not be detected;no serious liver and kidney function damage and other indexes are within the basic normal range;informed consent.The questionnaire is filled out by scanning the QR code of the"Gold data"platform questionnaire through a smart phone.The contents of the questionnaire include sociodemographic characteristics,sexual behaviors,PrEP related knowledge and attitude,PrEP missed pills,willingness of using intelligent electronic drug monitoring device and related social support,etc.Logistic regression analysis was used to analyze the factors affecting the willingness of using intelligent electronic drug monitors.The trend of high-risk behaviors’change among different PrEP type users were analyzed by?2trend test.The PrEP medication adherence was calculated at baseline,3 and 6 months of follow-up.The consistency between the results of different PrEP medication adherence measurement tools was analyzed by ROC curve and kappa coefficient.Eligible participants were randomly assigned to the intervention and the control group.For the intervention group,the intelligent electronic drug monitoring device was distributed,and the SMS channel system was opened.When there is a reminder of missed of dose detected by the intelligent electronic drug monitoring system,the system will automatically send real-time reminder information to the user’s mobile phone on condition of over time interval set by the user,when the set medication time is exceeded,and send it again in 30 minutes if no medication behavior occurs.For those who fail to show the medication refills in 30 mins after the second system reminder,the system will automatically send a reminder message to the responsible medical staff’s mobile phone.The responsible medical staff will check the missed dose and contact with the user to promote medication refills.If there is an observe of repeat medication,the medical staff will check with users with the reminding information from the system as well.For the control group,routine follow-up consultation will be provided.At the baseline,3 and 6-month follow-up points,all participants were required to complete an epidemiological questionnaire,which includes sociodemographic characteristics,sexual behaviors,PrEP related knowledge and attitude,missing dose of PrEP and related factors,social support,etc.During each follow-up,the medical staff counted the remaining tablets of each participant and collected 10ml blood samples to measure the concentration level of PrEP.The mixed linear model was used to evaluate the intervention effect of intelligent electronic drug monitors on PrEP medication adherence measured by self-report and pill count.The generalized linear mixed model was used to evaluate the intervention effect of intelligent electronic drug monitors on PrEP medication adherence measured by blood drug concentration.Results:1.The cross-sectional survey evaluated the willingness and related factors of using intelligent electronic drug monitoring device to monitor the PrEP medication adherence among MSM.A total of 572 MSM PrEP users were recruited.Among the eligible 560 MSM,312 cases were daily PrEP users,and 248 cases were on-demand PrEP users.The median age of the participants was 31（IQR 25-35）,80.0%（448/560）had a university degree or above,and 56.8%（318/560）were single.In the past three months,more than half of PrEP users had homosexual casual partners,and the proportion of condomless anal intercourse（CAI）was more than 40%;Nearly half of PrEP users have used new drugs.89.1%of PrEP users were willing to use the intelligent electronic drug monitoring device to monitor the PrEP medication adherence.Married or cohabiting with women（OR=3.64,95%CI:1.48-8.95）,little or no support from regular partners（OR=3.49,95%CI:1.57-7.73）and family members（OR=5.99,95%CI:1.31-27.35）,were obstacles to the unwillingness to use the intelligent electronic drug monitors to monitor the PrEP medication adherence.2.The prospective follow-up of the intelligent electronic drug monitors project obtained the PrEP medication adherence measured by different tools.Among the 442 PrEP users,255 cases were daily PrEP users,and 187 cases were on-demand PrEP users.The median age of the participants was 31 years old（IQR 25-35 years old）,81.7%（361/442）had a university degree or above,and 52.5%（232/442）were single.Among the 442 PrEP users who participated in the follow-up study at baseline,390（88.2%）PrEP users completed the third month follow-up,427（96.6%）PrEP users completed the sixth month follow-up.With the measurement of intelligent electronic drug monitors,it was found that the PrEP medication adherence of daily users increased from 87.5%（95%CI:85.1-90.0）at baseline to 92.8%（95%CI:90.0-95.6）at 3-momth follow up and 93.7%（95%CI:90.5-96.9）at 6-month follow up;the PrEP medication adherence of on-demand users was 83.7%（95%CI:78.8-88.6）at baseline,and 83.5%（95%CI:77.8-89.3）at 3-momth follow up and 85.7%（95%CI:78.7-92.7）at 6-momth follow up,respectively.Compared with the PrEP medication adherence measured by blood drug concentration,the intelligent electronic drug monitors showed a greater consistency of PrEP medication adherence than measured by self-report and pill count.Moreover,the unit cost of the intelligent electronic drug monitors was less（1,050 RMB）than half that of the unit cost of blood drug concentration（2,497 RMB）.3.The RCT study assessed the effect of the intelligent electronic drug monitor’s intervention on the medication adherence of MSM who use daily and on-demand PrEP.Among the eligible 516 PrEP users,255 cases were daily PrEP users,and 187 cases are on-demand PrEP users.The median age of the subjects was 31（IQR 25-35）,81.7%（361/442）had a university degree or above,and 52.5%（232/442）were single.During the study period,1,659 missed reminders were recorded by the intelligent electronic drug monitoring system,including 1,358 effective missed reminders（81.9%）,and 301 times invalid reminders from on demand group because there was no sexual activity after checking with the participants（18.1%）.In the recorded 1,346 effective missed reminders among daily PrEP users,530 missed doses were remedied through systematic intervention and 275 missed doses were remedied through medical staff.There were still 541 missed doses in the daily PrEP users.In the recorded 12 effective missed reminders among on-demand PrEP users,10 missed doses were remedied through systematic intervention and none from medical staff.There were still 2 missed doses in the on-demand PrEP users.Through the measurement of blood concentration,the proportion of good PrEP medication adherence（no less than 90%）in the control group of daily users was 70.9%（95%CI=64.9%-76.2%）,while the proportion of good PrEP medication adherence in the intervention group of daily users was 85.8%（95%CI=81.9%-89.0%）.There was significant difference between the two groups of daily users（p<0.0001）.The proportion of good PrEP medication adherence in the control group of on-demand users was 68.0%（95%CI=60.1%-74.9%）,and the proportion of good PrEP medication adherence in the intervention group of on-demand users was 80.5%（95%CI=74.0%-85.7%）.There was significant difference between the two groups of daily users（p=0.010）.The results of measuring by pill count were consistent with the results of blood drug concentration,and the proportion of PrEP medication adherence in the intervention group was higher than that in the control group（p<0.001）.For self-report,only the proportion of PrEP medication adherence in the intervention group of daily users was higher than that in the control group（p<0.05）,while there was no significant difference of PrEP medication adherence between the two groups among on-demand users（p>0.05）.Conclusion:1 The intelligent electronic drug monitoring device is a feasible and acceptable method to improve the PrEP medication adherence among MSM.Lack of support from family members and sexual partners are important obstacles to use the intelligent electronic drug monitoring device.In our study,we found that MSM realized the importance of PrEP medication adherence to reduce HIV new infections,but their high-risk sexual behaviors and self-reported missed dose exist.2.Self-report and pill count have an overreport of PrEP medication adherence.The PrEP medication adherence measured by blood drug concentration was costly and not suitable for clinical implementation.The PrEP medication adherence measured by intelligent electronic drug monitors was in a great consistency with PrEP medication adherence measured by blood drug concentration.3.The intelligent electronic drug monitoring with just-in-time monitoring and precise intervention functions can effectively improve the PrEP medication adherence for daily PrEP users and on demand PrEP users.There was no significant change of high-risk behaviors of MSM who are using PrEP. |
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