The Effect Of HIV Self-testing On HIV Testing And Condom Use Among Men Who Have Sex With Men Who Discontinue Oral Intaking Pre-exposure Prophylaxis: A Randomized Controlled Trial In China

Background:The risk of HIV infection among MSM is 25 times than the general population.To fully control the HIV epidemic in MSM,pre-exposure prophylaxis(PrEP)is widely used to reduce the risk of HIV infection in HIV-negative groups.However,the discontinuation of PrEP use exists,and it increases with prolonged time of PrEP use.It is observed that the high-risk sexual behaviors including the exposure to HIV infected partners,or sexually transmitted infections(STIs)due to risk compensation continued after the discontinuation of PrEP use among MSM.The delays in HIV testing may cause the transmission of HIV and STIs among MSM,which reflected a crucial need of continuous monitoring of HIV/STIs.WHO recommended that HIV Self-testing(HIVST)was an alternative approach to expand HIV testing coverage among high-risk groups.It was also recommended that HIV testing among the sexual partners of high-risk groups via HIVST secondary distribution.HIVST makes up for the deficiency of site-based HIV Testing(SBHIV),and is highly accepted among MSM using PrEP,and can effectively promote its HIV testing proportion and testing frequency.Meanwhile,it was demonstrated that the HIVST secondary distribution could improve the safe sexual behaviors and serosorting among MSM and their partners.In addition,the HIVST was widely used in PrEP users.However,there are few studies on the intervention of HIVST kits to those who stopped taking PrEP and their sexual partners.The further information regarding the behaviors and HIV/STIs situation after PrEP discontinuation among high-risk MSM and their sexual partners were needed.To understand the high-risk behavior characteristics and HIV/STIs testing may help develop effectively target interventions and improve expert consensus or guidelines on PrEP.Objective:Based on the multicenter China Real World Study of Oral PrEP(CROPrEP),this study intends to determine the changes in HIV testing behaviors,condom use,and sexual behaviors characteristics of MSM after PrEP discontinuation,HIV and STIs prevalence and evaluate the effects of online distribution of HIVST on these behaviors.The feasibility of HIVST delivery among the sexual partners of MSM who discontinued the PrEP use.Methods:In the first chapter of this study,a longitudinal MSM cohort among MSM after PrEP discontinuation was developed through the We Chat platform.MSM who discontinued the PrEP use and did not take PrEP for nearly 3 months in the CROPrEP program in China through online and offline recruitment were recruited.Instructions of the study,the electronic informed consent,and 10 ml blood sample were required at the baseline.Online self-filled epidemiological questionnaire was required,which including social demographic information,sexual behaviors,HIV/STIs testing information,and other HIV-related behavior information within three months.Then it was compared with the last visit data of PrEP using.Generalized estimating equation(GEE model)was used to compare the frequency of sexual behavior,condom use,HIV testing rate,and frequency of Chinese MSM before and after PrEP discontinuation.The logistic regression model was used to analyze the factors of HIV testing within the past three months after PrEP discontinuation,and the multivariate regression model adjusted age,education,monthly income,and previous PrEP dose.A two-sided P<0.05 was defined as a statistical significance,and a two-sided P<0.1 was defined as marginal statistical significance.The second chapter of this study is a randomized controlled trial study of HIVST kits delivery among MSM after PrEP discontinuation.The recluded discontinued PrEP users were randomly divided into two groups using the random number,and their grouping information was announced to the investigator and study subjects by the envelope method.The intervention group received HIVST kits by mailing(they could continue to apply after feedback on the results as required),while the control group received free SBHIV.A total of 6 months of follow-up was conducted,and an online epidemiological survey was conducted every three months to collect information within the past three months,which including HIV/STIs testing and sexual behavior among those who discontinued the PrEP.Chi-square test was used to compare the differences in HIV/STIs testing rates,HIV infection status notification or information,partner-seeking characteristics,and CAI incidence between two groups at baseline and after the intervention.Then,the effect of HIVST on HIV testing behavior and condom use in MSM PrEP discontinuation was investigated.At the same time,the linear-by-Linear Association chi-square trend was used to analyze the trend of HIV/STIs testing rate and the incidence of CAI in the two groups during follow-up.The third chapter of this study explored a prospective cohort study that extrapolated the HIVST strategy to promote the feasibility of Partner HIV Testing(PHT)in the PrEP discontinuation MSM population.The MSM PrEP discontinuation population is regarded as the sharer of the HIVST kit.Two HIVST kits were provided and encouraged to conduct a couple testing or share with their sexual partners or can be used together with their partners.Partners who used the HIVST kits and with result feedback and epidemiological questionnaire completed were regarded as eligible recipients of HIVST.We also collected the geographic location,the serostatus of HIV,TP and HBV/HCV,and sexual behavior characteristics.After each sexual partner and his sharer are matched with each other,the distribution of HIVST strategy is regarded as successful.Frequency and proportion were used to describe the demographic information and behavioral characteristics.The participants needed to complete online follow-up for getting HIVST sharing and their own behavior information at 3 and 6 months after the enrollment.Mean±standard deviation were used to measure the central tendency.Generalized linear mixture model and generalized estimation equation were used to analyze the characteristics differences between sharers and unshared participants and the related factors.The geographic information of sharers and their sexual partners was collected to draw regional maps and flow maps to analyze the secondary transmission path of HIVST.Univariate and multivariate logistic regression models were used to analyze the factors with having HIV test among these sexual partners in the past six months,and multivariate regression was used to adjust age,education,and marital status.Results:1.From July 2020 to December2020,a total of 620 MSM who discontinued PrEP were recruited in four major cities of Shenyang,Beijing,Shenzhen,and Chongqing.(1)Social background information:The median age of the participants was 31 years old(IQR:26–37 years old),83.4%(511/620)of them had undergraduate or college degree,and above,42.4%(263/620)of the monthly income were more than 6000-yuan(RMB),77.6%(481/620)self-reported sexual orientation as homosexual,the previous doses of PrEP were51.8%(321/620)daily and 48.2%(299/620)event-driven.(2)Infection rates:the infection rates of HBV(1.3%vs.0.6%)and HCV(1.1%vs.0%)in MSM after PrEP discontinuation were higher than those before PrEP discontinuation,and the infection rate of TP was little reduced(2.4%vs.4.5%).(3)Differences in sexual behaviors before and after PrEP discontinuation:Compared with before PrEP discontinuation,the frequency of sexual acts“every week”increased(39.2%VS.32.6%,OR=1.1,95%CI:1.0-1.2,P=0.018),in the past three months after PrEP discontinuation.61.9%(384/620)of participants had sex with a regular partner,and the incidence of CAI was 56.5%(217/384);41.8%(259/620)of participants had sex with a casual partner,and the incidence of CAI was 47.1%(122/259).The proportion of group sex higher than before(15.2%VS.11.5%,OR=1.4,95%CI:1.0-1.9,P=0.050),and the incidence of group sex CAI was 36.2%(34/94).(4)Difference in HIV testing behavior in the past three months:Compared with before PrEP discontinuation,the HIV testing rate decreased significantly(68.0%VS.74.5%,OR=0.7,95%CI:0.6-0.9,P=0.015),HIVST use rate decreased significantly(48.7%VS.68.5%,OR=0.4,95%CI:0.6-0.5,P<0.001),and HIVST use times“>2”decreased(29.5%VS.38.4%,OR=0.9,95%CI:0.8-1.0,P=0.022);The proportion of TP testing times“≥2”decreased after PrEP discontinuation,and the difference was marginally statistically significant(51.1%VS.59.0%,OR=1.4,95%CI=1.0-2.0,P=0.089).(5)The related factors with HIV testing in the past three months after PrEP discontinuation are as follow:High frequency of sexual acts(weekly sexual activity VS.no sex)(AOR=1.9,95%CI:1.0-3.5),having STIs test(VS.not tested)(OR=1.7,95%CI:1.2-2.4),having TP test(VS.not tested)(OR=1.7,95%CI:1.2-2.4),willing to accept HIVST(VS.unwilling to accept)(AOR=2.0,95%CI:1.0-3.8).2.In the RCT study,we found that the effect of HIVST on HIV testing behavior,condom use,and knowing partners HIV status behavior in PrEP-discontinued MSM.Between December 2020-July 2021,a total of 620 PrEP-discontinued MSM at baseline,and 601 of them completed the last follow-up online visit(6 month after enrollment),the retention rate was 96.9%(601/620),and the cumulative was 404.68 person-years(PY).During the follow-up period,six people had HIV-1 positive conversion,and the cumulative incidence density was1.5(95%CI:0.6-3.4)/100PY,and 13 people had TP seroconversion,and the cumulative incidence density was 3.2(95%CI:0.6-3.4)/100PY.1.8-5.6)/100PY.A total of 1490 HIVST reagents were mailed,of which 1235 received correct feedback,with a feedback rate of 82.9%(1235/1490).(1)The effect of HIVST intervention:Compared with the control group,the HIVST intervention group had higher HIV testing rate in the past three months(87.2%VS.60.5%,P<0.001),and the HIV testing frequency was higher(3.1±2.3 times VS.1.9±2.2 times,P<0.001),the HIVST usage rate was higher(80.8%VS.46.4%,P<0.001);(2)The effect of informed HIV status behavior:The proportion of knowing the HIV testing results each other was higher than the control group(38.7%VS.20.1%,P<0.001),while the HIV results of inform partners(36.7%VS.22.8%,P<0.001)and the HIV results of partners(68.0%VS.55.6%,P=0.002),the HIVST intervention group was significantly higher than the control group.(3)Sexual behavior:Compared with the control group,the HIVST intervention group had a lower proportion of“every week”sexual behavior frequency(34.7%VS.48.0%,P<0.001),and the incidence of CAI was lower(58.9%VS.62.1%,P<0.001),the rate of group sex CAI(35.7%VS.78.0%,P<0.001),anal bleeding(17.5%VS.26.0%,P=0.012),and enema was lower(54.2%VS.74.0%,P<0.001).Linear chi-square trend analysis showed that the proportion of HIV testing rate(χ~2=31.166,P<0.001)and HIVST usage rate(χ~2=82.107,P<0.001)in the HIVST intervention group showed a significant increasing trend with time.In the control group,STIs(χ~2=6.174,P=0.013)and TP testing rate(χ~2=5.863,P=0.015)showed a significant downward trend with time,while the incidence of group intercourse CAI showed a significant upward trend with time(χ~2=1.671,P=0.001).3.During the 3rd-month and 6th-month follow-up,300 and 297 participants reported sharing HIVST kits with their partners respectively,and the sharing rates were 47.0%(141/300)and 35.0%(104/297)respectively.In sum,245 of the 597 participants successfully shared,and the cumulative sharing rate was 41.0%(245/597).167 of the 301partners who successfully shared reported the HIVST results,with a feedback rate of 55.5%(167/301).The satisfaction rate for this Internet-based HIVST secondary distribution strategy is as high as 100%,of which 89.2%(149/167)are very satisfied.During the period,the positive rates of HIV and TP were 2.4%(4/167)and 4.2%(7/167).(1)Characteristics of sharer:the rate of HIV testing of sharer and sexual partner was 63.2%higher than that of non-sharer(sharer VS.Unshared.79.5%VS.16.3%,P<0.001),the rate of HIV awareness of partners was 82.2%higher than that of non-sharer(sharer VS.non-sharer,84.6%vs.2.3%,P<0.001),and the difference was statistically significant.(2)Analysis of factors:Having HIV testing in the last 3 months(VS.Not testing)(AOR=4.1,95%CI:2.1-8.4,P<0.001),use the HIVST(VS.unused)(AOR=6.5,95%CI:3.4-12.8,P<0.001),with STIs related symptoms(VS.no symptoms)(AOR=2.5,95%CI:1.5-4.1,P<0.001),CAI with a regular partner(VS.consistent condom use with a regular partner)(AOR=1.6,95%CI:1.1-2.5,P=0.031)were associated with HIVST sharing among PrEP discontinuation participants during cohort follow-up(3)The coverage of PHT is more extensive:According to the map of the geographical location,HIVST kits are transmitted to 19 provinces and cities across China,and concentrated in Liaoning,Beijing,Chongqing,and Guangdong.The shortest transmission route is intra-provincial transmission,with a transmission rate of 15.9%(26/167).The longest transmission route is from Shenzhen,Guangdong,to Changchun,Jilin,with a total distance of about3073.69km.(4)Partners information:the median age was 27(IQR:23-32),76.0%(127/167)self-reported sexual orientation was homosexual,and 40.7%(68/167)had an intimate relationship status with men.In the past three months,35.5%(59/167)of the sexual partners had sex every week,and 52.1%(87/167)searched for sexual partners via the Internet,with an average of 2.3±2.1 sexual partners,42.7%(61/167)had multiple sexual partners.70.1%(117/167)of sexual partners reported having anal or oral sex with their regular partners,and the incidence of CAI was 51.4%(60/117).And 25.7%(43/167)of sexual partners reported having sex with their casual partners,of which the incidence of CAI was 27.9%(12/43);77.8%(130/167)self-assessed the risk of HIV infection as no risk or low risk.In the past six months(except for this time),31.7%(53/167)of partners did not have HIV testing,and the HIVST usage rate was 61.1%(102/167),24.0%(40/167)of MSM sexual partners had never been tested via HIVST before.Through the secondary distribution of HIVST,85.0%(142/167)knew the HIVST result of the sharer,and 96.4%(161/167)of the MSM sexual partners also informed the sharer of their test results,and79.0%(132/167)of the sexual partners use HIVST together with their sharers and inform each other about the results.(5)The related factors of not being tested for HIV with a partner in the past six months are group sex(AOR=3.6,95%CI:1.5-8.3,P=0.003)and only oral sex with regular partners(AOR=9.8,95%CI:1.1-91.0,P=0.045).Conclusion:1.Among MSM who discontinued the PrEP use,the proportion of CAI is high while the HIV testing proportion is low,which may increase the risk of HIV transmission.It is recommended that targeted and active sentences regarding health knowledge and condoms use via internet platforms such as phone calls,text messages,and We Chat are necessary to improve the performance PrEP continuation.The combination of STIs/HIV self-testing is as an effective approach for expanding the testing coverage.The in-depth understanding of the behavioral characteristics of Chinese MSM after PrEP discontinuation could be used as a reference to provide scientific evidence to PrEP intervention time or post-cessation evaluation.2.The online distribution of HIVST kits in high-risk PrEP-discontinued MSM significantly improve the HIV/STIs testing coverage and condom use.Meanwhile,the online distribution of HIVST could reduce the high-risk behaviors and the usage of serosorting.HIVST would be an effective way to increase HIV testing and reduce the risk behaviors in the implementation of PrEP program.3.In this study,the HIVST strategy was extrapolated to the sexual partners group of PrEP-discontinued MSM populations to verify the feasibility,effectiveness,and coverage of this testing model.High-risk MSM hidden partners were captured through the non-contact HIVST secondary distribution strategy,which effectively promoted the mutual testing and serosorting between MSM and their sexual partners,which provide favorable evidence for implementing of PrEP discontinuation.