Trajectories of anxiety and depression among Chinese men who have sex with men on pre-exposure prophylaxis: a group-based trajectory model approach.

BACKGROUND: Anxiety and depression can influence adherence to Pre-exposure Prophylaxis (PrEP). However, there is limited research on the temporal dynamics of anxiety and depression among men who have sex with men (MSM) using PrEP. METHODS: From December 2018 to November 2020, we administered the Hospital Anxiety and Depression Scale (HADS) to participants in the China Real-World Oral Intake of PrEP (CROPrEP) to measure their anxiety and depression levels. The group-based trajectory model (GBTM) depicted the dynamic changes of anxiety and depression scores over time. RESULTS: A total of 1023 MSM were included, with 4523 follow-up assessments. The GBTM categorized the trajectories into three distinct patterns: consistently low (54.8% for anxiety, 60.7% for depression), consistently moderate (39.3% for anxiety, 31.4% for depression), and high but bell-shaped (5.9% for anxiety, 7.9% for depression). Higher anxiety levels were associated with being aged 18-30 years old, earning less than US$619 per month, female-identifying, adopting the bottom sexual role with men, and having two or more anal sex partners in the past three months; similarly, higher depression levels correlated with a monthly income under US$619, female-identifying, sexual behavior as bottom and a positive syphilis at baseline. PrEP adherence was notably lower in the high but bell-shaped anxiety and depression group compared to the other groups, particularly at the 12th-month follow-up. CONCLUSIONS: Close monitoring of anxiety and depression levels in MSM on PrEP is crucial. Provision of targeted mental health support is essential to enhance PrEP effectiveness.

First complete-genome documentation of HIV-1 intersubtype superinfection with transmissions of diverse recombinants over time to five recipients.

Human immunodeficiency virus type 1 (HIV-1) recombinants in the world are believed to be generated through recombination between distinct HIV-1 strains among coinfection or superinfection cases. However, direct evidence to support transmission of HIV-1 recombinants from a coinfected/superinfected donor to putative recipient is lacking. Here, we report on the origin and evolutionary relationship between a set of recombinants from a CRF01_AE/CRF07_BC superinfected putative donor and diverse CRF01_AE/CRF07_BC recombinants from five putative recipients. Interviews on sociodemographic characteristics and sexual behaviors for these six HIV-1-infected men who have sex with men showed that they had similar ways of partner seeking: online dating sites and social circles. Phylogenetic and recombination analyses demonstrated that the near-full-length genome sequences from six patients formed a monophyletic cluster different from known HIV-1 genotypes in maximum likelihood phylogenetic trees, were all composed of CRF01_AE and CRF07_BC fragments with two common breakpoints on env, and shared 4-7 breakpoints with each other. Moreover, 3' half-genomes of recombinant strains from five recipients had identical/similar recombinant structures with strains at longitudinal samples from the superinfected donor. Recombinants from the donor were paraphyletic, whereas five recipients were monophyletic or polyphyletic in the maximum clade credibility tree. Bayesian analyses confirmed that the estimated time to the most recent common ancestor (tMRCA) of CRF01_AE and CRF07_BC strains of the donor was 2009.2 and 2010.7, respectively, and all were earlier than the emergence of recombinants from five recipients. Our results demonstrated that the closely related unique recombinant forms of HIV-1 might be the descendent of a series of recombinants generated gradually in a superinfected patient. This finding highlights the importance of early initiation of antiretroviral therapy as well as tracing and testing of partners in patients with multiple HIV-1 infection.

Molecular Network Analysis Discloses the Limited Contribution to HIV Transmission for Patients with Late HIV Diagnosis in Northeast China.

In the "treat all" era, the high rate of late HIV diagnosis (LHD) worldwide remains an impediment to ending the HIV epidemic. In this study, we analyzed LHD in newly diagnosed people living with HIV (PLWH) and its impact on HIV transmission in Northeast China. Sociodemographic information, baseline clinical data, and plasma samples obtained from all newly diagnosed PLWH in Shenyang, the largest city in Northeast China, between 2016 and 2019 were evaluated. Multivariate logistic regression analysis was performed to identify risk factors associated with LHD. A molecular network based on the HIV pol gene was constructed to assess the risk of HIV transmission with LHD. A total of 2882 PLWH, including 882 (30.6%) patients with LHD and 1390 (48.2%) patients with non-LHD, were enrolled. The risk factors for LHD were older age (≥ 30 years: p < .01) and diagnosis in the general population through physical examination (p < .0001). Moreover, the molecular network analysis revealed that the clustering rate (p < .0001), the fraction of individuals with ≥ 4 links (p = .0847), and the fraction of individuals linked to recent HIV infection (p < .0001) for LHD were significantly or marginally significantly lower than those recorded for non-LHD. Our study indicates the major risk factors associated with LHD in Shenyang and their limited contribution to HIV transmission, revealing that the peak of HIV transmission of LHD at diagnosis may have been missed. Early detection, diagnosis, and timely intervention for LHD may prevent HIV transmission.

Willingness to take long-acting injectable pre-exposure prophylaxis among men who have sex with men who participated in the CROPrEP study: a cross-sectional online study.

INTRODUCTION: Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. OBJECTIVE: The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. METHODS: MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. RESULTS: A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. CONCLUSION: LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.

Association between rectal douching and HIV acquisition: the mediating role of condom use and rectal bleeding in a national online sample of Chinese men who have sex with men.

OBJECTIVES: Previous studies have demonstrated that rectal douching (RD) is associated with HIV acquisition among men who have sex with men (MSM). However, the precise mechanism underlying the association between RD and HIV remains unclear. METHODS: We recruited participants over WeChat from October 2017 to October 2018. Respondents received mailed HIV self-testing kits, uploaded images of HIV self-test results and completed an online electronic questionnaire simultaneously. The questionnaire assessed sociodemographic characteristics, RD practices and sexual risk behaviours. HIV status was measured as the result of the HIV self-testing. The Baron and Kenny statistical method was used to assess the association between RD and HIV, controlling for condomless anal intercourse (CAI) and rectal bleeding. RESULTS: Of 1365 participants, 39.93% (545/1365) reported RD in the past 6 months, 60.07% had multiple male sexual partners and 43.08% had CAI in the past 6 months. The prevalence of HIV, based on self-testing, was 3.37% (46/1365). Multivariable logistic analysis showed RD was significantly associated with bottom sexual role (adjusted OR (aOR) 14.0; 95% CI 9.8 to 20.2), having multiple male sexual partners (aOR 1.8; 95% CI 1.4 to 2.2), CAI (aOR 1.3; 95% CI 1.0 to 1.6), rectal bleeding (aOR 2.0; 95% CI 1.6 to 2.6) and HIV infection (aOR 1.9; 95% CI 1.0 to 3.4). Baron and Kenny analysis found both CAI (aOR 2.2; 95% CI 1.2 to 4.1) and rectal bleeding (aOR 1.9; 95% CI 1.0 to 3.4) play a mediating role in the association between RD and HIV. CONCLUSIONS: Our study results confirmed the relationship between RD and HIV, and found CAI and rectal bleeding mediated HIV infection in Chinese MSM who douched. Strategies should be encouraged to strengthen health education and reduce high-risk sexual behaviour in order to reduce the risk of HIV in MSM who use enemas. Rectal microbicides may represent an efficient means of providing HIV prophylaxis among MSM.

Feasibility of Indirect Secondary Distribution of HIV Self-test Kits via WeChat Among Men Who Have Sex With Men: National Cross-sectional Study in China.

BACKGROUND: HIV self-testing (HIVST) kits are common in key sexually active populations. Direct secondary distribution of HIVST kits (DSDHK) is effective in improving the uptake of HIVST. However, there are concerns about the various limitations of DSDHK, including limited geographic reach, payment problems, and need for face-to-face interactions. OBJECTIVE: In this study, we aim to evaluate the feasibility and characteristics of indirect secondary distribution of HIVST kits (ISDHK) via WeChat (distributing HIVST application links and follow-up HIVST kits to partners) among men who have sex with men (MSM). METHODS: From October 2017 to September 2019, an HIVST recruitment advertisement was disseminated on the WeChat social media platform to invite MSM to apply for the HIVST kits (referred to as index participants [IPs]). All MSM participants were encouraged to distribute the HIVST application link to their friends and sexual partners (referred to as alters) through their social networks. All the alters were further encouraged to continue distributing the HIVST application link. All participants paid a deposit (US $7), which was refundable upon completion of the questionnaire, and uploaded the test results via a web-based survey system. RESULTS: A total of 2263 MSM met the criteria and successfully applied for HIVST. Of these, 1816 participants returned their HIVST results, including 1422 (88.3%) IPs and 394 (21.7%) alters. More alters had condomless anal intercourse, a higher proportion of them had never previously tested for HIV, and they showed a greater willingness to distribute HIVST kits to their sexual partners (P=.002) than the IPs. After controlling for age, education, and income, the alters had a greater proportion of MSM who had never tested for HIV before (adjusted odds ratio [aOR] 1.29, 95% CI 1.00-1.68), were more willing to distribute the HIVST application link (aOR 1.71, 95% CI 1.21-2.40), had a lower number of sexual partners (aOR 0.71, 95% CI 0.57-0.90), and were less likely to search for sexual partners on the web (aOR 0.78, 95% CI 0.60-1.02) than IPs. In comparison, the rates of reactive HIVST results, conducting HIV confirmatory tests, HIV seropositivity, and initiation of HIV antiretroviral therapy were similar for IPs and alters. CONCLUSIONS: The ISDHK model of distributing HIVST application links among the MSM population via social media is feasible. The ISDHK model should be used to supplement the DSDHK model to enable a greater proportion of the MSM population to know their HIV infection status.

Internet-Based HIV Self-Testing Among Men Who Have Sex With Men Through Pre-exposure Prophylaxis: 3-Month Prospective Cohort Analysis From China.

BACKGROUND: Routine HIV testing accompanied with pre-exposure prophylaxis (PrEP) requires innovative support in a real-world setting. OBJECTIVE: This study aimed to determine the usage of HIV self-testing (HIVST) kits and their secondary distribution to partners among men who have sex with men (MSM) in China, who use PrEP, in an observational study between 2018 and 2019. METHODS: In 4 major cities in China, we prospectively followed-up MSM from the China Real-world oral PrEP demonstration study, which provides daily or on-demand PrEP for 12 months, to assess the usage and secondary distribution of HIVST on quarterly follow-ups. Half of the PrEP users were randomized to receive 2 HIVSTs per month in addition to quarterly facility-based HIV testing. We evaluated the feasibility of providing HIVST to PrEP users. RESULTS: We recruited 939 MSM and randomized 471 to receive HIVST, among whom 235 (49.9%) were daily and 236 (50.1%) were on-demand PrEP users. At baseline, the median age was 29 years, 390 (82.0%) men had at least college-level education, and 119 (25.3%) had never undergone facility-based HIV testing before. Three months after PrEP initiation, 341 (74.5%) men had used the HIVST provided to them and found it very easy to use. Among them, 180 of 341 (52.8%) men had distributed the HIVST kits it to other MSM, and 132 (51.6%) among the 256 men who returned HIVST results reported that used it with their sexual partners at the onset of intercourse. Participants on daily PrEP were more likely to use HIVST (adjusted hazard ratio=1.3, 95% CI 1.0-1.6) and distribute HIVST kits (adjusted hazard ratio=1.3, 95% CI 1.1-1.7) than those using on-demand PrEP. CONCLUSIONS: MSM who used PrEP had a high rate of usage and secondary distribution of HIVST kits, especially among those on daily PrEP, which suggested high feasibility and necessity for HIVST after PrEP initiation. Assuming that fourth-generation HIVST kits are available, HIVST may be able to replace facility-based HIV testing to a certain extent. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800020374; https://www.chictr.org.cn/showprojen.aspx?proj=32481. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-036231.

Increasing Condomless Anal Intercourse and HIV Prevalence Among Men Who Have Sex with Men Who Have Never Been Tested for HIV Before: A Serial Cross-Sectional Study in Shenyang, China from 2012 to 2016.

Despite the high HIV incidence among men who have sex with men (MSM) in China, over half of MSM have never been tested for HIV before (MSMNT). Through a serial cross-sectional study from 2012 to 2016 in Shenyang, China, we studied 1036 MSMNT, and diagnosed 16.2% (168/1036) with HIV. The percentage of MSMNT who had condomless anal intercourse (CAI) in the past year increased from 42.1% (130/309) in 2012 to 63.4% (102/161) in 2016 (P < 0.001). 61.9% (104/168) of HIV-positive MSMNT had CAI and this percentage remained constant for the study period (P = 0.593). 53.3% (463/868) of HIV-negative MSMNT had CAI and this percentage significantly increased over the study period (P < 0.001). Encouraging HIV testing in this key subset through online HIV risk self-evaluation tools and HIV self-testing kits may help mitigate the overall MSM HIV incidence.

Association of nitrite inhalants use and unprotected anal intercourse and HIV/syphilis infection among MSM in China: a systematic review and meta-analysis.

BACKGROUND: Nitrite inhalant use is very common among men who have sex with men (MSM) in China. However, there is lack of national representative data on use among Chinese MSM, and the mechanism of how nitrite inhalant use impacts HIV infection in MSM is unclear. This meta-analysis aims to understand the characteristics of Chinese MSM nitrite inhalant users and to determine the associations between nitrite inhalant use and sexual behaviors, the prevalence of HIV, and the prevalence of syphilis. METHODS: We searched PubMed, Web of Science, Chinese National Knowledge Infrastructure, Chinese Wanfang Data, and VIP Chinese Journal Database for relevant literature published from January 1985 to December 2017. RESULTS: Fifteen eligible studies, with a total of 18,981 Chinese MSM participants, were included. Compared with nitrite inhalant nonusers, users were more likely to be younger, have a higher level of education, and seek sexual partners using the Internet. Nitrite inhalant users were more likely to engage in high-risk sexual behaviors, including condomless anal intercourse (odds ratio [OR] = 1.33), group sex (OR = 2.26), and commercial intercourse (OR = 1.50). Nitrite inhalants users had a higher prevalence of HIV (OR = 1.83), higher prevalence of syphilis (OR = 1.38) and had higher lifetime HIV testing rates (OR = 1.33) compared with nonusers (each p < 0.05). CONCLUSIONS: Nitrite inhalant users have higher HIV and syphilis prevalence by increasing levels of high-risk sexual behaviors. China should expand HIV testing, treatment as prevention (TasP), and Pre-exposure prophylaxis (PrEP) among MSM, especially among nitrite inhalants using MSM, to reduce their risk of HIV infection and transmission.

Real-time monitoring and just-in-time intervention for adherence to pre-exposure prophylaxis among men who have sex with men in China: a multicentre RCT study protocol.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is an effective biomedical strategy to prevent transmission of HIV infection, although medication adherence remains a challenge. We present the protocol for a multicentre randomised controlled trial to measure the effectiveness of a real-time monitoring and just-in-time intervention on medication adherence among PrEP users in China. METHODS: Study participants will include 1000 men who have sex with men (MSM) from four cites in China (Shenyang, Beijing, Chongqing and Shenzhen) attending a tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) PrEP project as part of a real-world, prospective multicentre cohort study (CROPrEP). Participants will be randomised into the intervention and control arms in a 1:1 ratio. Participants in the intervention arm will be provided with remote real-time monitoring equipment that triggers twice just-in-time SMS (Short Messaging Service) medication reminders to PrEP users every half an hour when a scheduled dosage is missed, and followed with just-in-time SMS medication reminders to clinicians half an hour when there is no supplement after the second just-in-time SMS reminder to PrEP users. Clinicians will initiate individualised telephone intervention as soon as possible upon receipt of the just-in-time SMS missed dose alert. Those in the control arm will only receive generic weekly SMS reminders. The study will last 6 months. Participants will be seen at follow-up visits at three and 6 months. Trial outcomes to be measured include self-reported adherence assessed via questionnaire and pill counts, as well as drug concentration test results. DISCUSSION: Medication adherence is critical to achieve optimal benefits from PrEP. This study will be the first individualised behaviour intervention using real-time technology to increase adherence among MSM PrEP users globally. If found effective, a real-time monitoring and just-in-time intervention system may be utilized for improving adherence and thus effectiveness of global PrEP application. TRIAL REGISTRATION: This study registered at ClinicalTrials.gov ( ChiCTR1900025604 ) on September 2, 2019.

Correction: Risk-Taking Behaviors and Adherence to HIV Pre-Exposure Prophylaxis in Users of Geosocial Networking Apps: Real-World, Multicenter Study.

[This corrects the article DOI: 10.2196/22388.].

Risk-Taking Behaviors and Adherence to HIV Pre-Exposure Prophylaxis in Users of Geosocial Networking Apps: Real-World, Multicenter Study.

BACKGROUND: Over half of men who have sex with men (MSM) use geosocial networking (GSN) apps to encounter sex partners. GSN apps' users have become a unique large subpopulation among MSM for interventions concerning HIV prevention and control. Pre-exposure prophylaxis (PrEP) is a promising measure for HIV prevention, especially for MSM, but its effectiveness largely depends on medication adherence. However, little is known about PrEP adherence among GSN apps' users, which is critical to addressing the overall optimization of PrEP compliance outside of clinical trials in the context of large-scale implementation. OBJECTIVE: The objective of this study is to understand the correlation between GSN apps' use and medication adherence among MSM receiving PrEP, with the aim to increase their awareness about PrEP use in order to increase adherence. METHODS: This study based on the China Real-world Oral intake of PrEP (CROPrEP) project, a multicenter, real-world study of Chinese MSM on daily and event-driven PrEP. Eligible participants completed a detailed computer-assisted self-interview on sociodemographic, GSN apps' use, and sexual behavior. Then participants were followed up for 12 months and assessed for various characteristics (eg, PrEP delivery, adherence assessment, PrEP coverage of sexual activities, and regimens switch). A generalized estimation equation was used to analyze the predictors of medication adherence and regimen conversion among GSN apps' users and nonusers. RESULTS: At baseline, 756 of the 1023 eligible participants (73.90%) reported primarily using GSN apps to seek sexual partners, and GSN apps' users are more likely to have high-risk behaviors such as multiple sex partners and condomless anal intercourse than other nonusers (all P<.05). During follow-up, GSN apps' users had a significantly low level of pill-counting adherence than nonusers (adjusted odds ratio [aOR] 0.8, 95% CI 0.6-1.0, P=.038). In the event-driven group, GSN apps' users had marginally lower levels of self-reported adherence (aOR 0.7, 95% CI 0.4-1.0, P=.060) and lower PrEP coverage of sexual practices (aOR 0.6, 95% CI 0.4-1.0, P=.038). Additionally, GSN apps' users seemed more likely to switch from event-driven to daily regimen (aOR 1.8, 95% CI 0.9-3.3, P=.084). CONCLUSIONS: GSN apps' users are highly prevalent among MSM, despite their higher sexual risk and lower adherence levels, suggesting that eHealth needs to be introduced to the GSN platform to promote PrEP adherence. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IIN-17013762; https://tinyurl.com/yy2mhrv4. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12879-019-4355-y.

The combination of CXCL9, CXCL10 and CXCL11 levels during primary HIV infection predicts HIV disease progression.

BACKGROUND: Chemokines are small chemotactic cytokines involved in inflammation, cell migration, and immune regulation in both physiological and pathological contexts. Here, we investigated the profile of chemokines during primary HIV infection (PHI). METHODS: Fifty-four participants with blood samples before and during HIV infection and clinical information available were selected from an HIV-negative man who have sex with men (MSM) prospective cohort. Thirty chemokines and 10 cytokines were measured pre- and post-HIV infection in the same individuals using a Bio-Plex Pro™ Human Chemokine Panel. RESULTS: Levels of 18 chemokines/cytokines changed significantly during PHI relative to pre-HIV infection levels; 14 were up-regulated and 4 down-regulated. Among them, CXCL9, CXCL10, and CXCL11 were the most prominently raised. Levels of CXCL9 and CXCL10 were much higher in the high-set point group (log viral load (lgVL) ≥ 4.5) than those in the low-set point group (lgVL < 4.5) and levels of CXCL9, CXCL10, and CXCL11 were higher in the low-CD4+ T-cell count group (CD4+ T-cell count ≥ 500). A formula to predict HIV disease progression using a combination panel comprising CXCL9, CXCL10, and CXCL11 was developed, where risk score = 0.007 × CXCL9 + 0.004 × CXCL10 - 0.033 × CXCL11 - 1.724, with risk score values higher than the cutoff threshold (0.5211) indicating more rapid HIV disease progression. CONCLUSIONS: A panel of plasma CXCL9, CXCL10, and CXCL11 measured during primary HIV-1 infection could predict long-term HIV disease prognosis in an MSM group and has potential as a novel biomarker in the clinic.

Protocol for a multicenter, real-world study of HIV pre-exposure prophylaxis among men who have sex with men in China (CROPrEP).

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a promising and effective tool to prevent human immunodeficiency virus (HIV) transmission; however, context-specific data to guide optimal implementation are currently lacking in China. This study aims to systematically collect comprehensive, empirical data to determine effective ways to implement PrEP among at-risk men who have sex with men (MSM) in China. METHODS: The CROPrEP project, a real-world study of PrEP use, will recruit 1000 high-risk HIV-negative MSM participants from four cities in China, who will be able to choose between daily or event-driven dosing regimens, according to their preference. Participants will be followed up at months 1, 3, 6, 9, and 12 for PrEP provision, clinical evaluation, laboratory testing (e.g., emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) concentrations, and HIV/sexually transmitted infections), alongside detailed, self-administered online questionnaires regarding sexual behaviors, adherence, and attitudes. Online weekly notes will be used to record pill use and sexual practice. Various measurements will be triangulated to assess adherence, including: self-reported adherence, pill count, and drug concentration. A propensity score matching model will be fitted to examine the effectiveness of PrEP use in HIV seroconversion compared with non-PrEP users selected from a local expanding cohort study of HIV-1-negative MSM at participating research centers. Analyses using a generalized estimating equation model will focus on elucidation of the cascade of PrEP implementation, effectiveness, safety, and possible effects of PrEP use on sexual behaviors. This study will provide a comprehensive assessment of real-world PrEP use among Chinese MSM, to develop guidelines and strategies for PrEP implementation in China. DISCUSSION: The CROPrEP project is the first study of the TDF/FTC combination as PrEP in China, which will provide primary data on PrEP implementation, including: the cascade of PrEP use, "real-world" effectiveness, adherence, and safety. The findings from this study have potential to be vital for promoting the integration of PrEP within the portfolio of HIV prevention interventions and developing guidance on PrEP implementation in China. TRIAL REGISTRATION: ChiCTR-IIN-17013762 (Chinese Clinical Trial Registry). Date of registration: 8 December 2017.

Efficacy and cost-effectiveness of early antiretroviral therapy and partners' pre-exposure prophylaxis among men who have sex with men in Shenyang, China: a prospective cohort and costing study.

BACKGROUND: Biomedical interventions such as antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are highly effective for prevention of human immunodeficiency virus (HIV) infection. However, China has not released national PrEP guidelines, and HIV incidence among men who have sex with men (MSM) is unchanged despite substantial scale-up of ART. We evaluated reductions in HIV transmission that may be achieved through early initiation of ART plus partners' PrEP. METHODS: Six intervention scenarios were evaluated in terms of their impact on HIV transmission and their cost-effectiveness for 36 months post-infection. Three scenarios were based on observed data: non-ART, standard-ART, and early-ART. Another three scenarios were based on observed and hypothetical data: non-ART plus partners' PrEP, standard-ART plus partners' PrEP, and early-ART plus partners' PrEP. The number of onward transmissions was calculated according to viral load and self-reported sexual behaviors, and calibrated by the prevalence and incidence of HIV among Chinese MSM. Cost-effectiveness outcomes were quality-adjusted life-years (QALYs) and cost-utility ratio (CUR). RESULTS: The estimated number of onward transmissions by every 100 HIV-positive cases 36 months post-infection was 41.83 (95% credible interval: 30.75-57.69) in the non-ART scenario, 7.95 (5.85-10.95) in the early-ART scenario, and 0.79 (0.58-1.09) in the early-ART plus partners' PrEP scenario. Compared with non-ART, the early-ART and early-ART plus partners' PrEP scenarios were associated with an 81.0 and 98.1% reduction in HIV transmission, and had a CUR of $12,864/QALY and $16,817/QALY, respectively. CONCLUSIONS: Integrated delivery of early ART and sexual partners' PrEP could nearly eliminate HIV transmission and reduce costs during the first 36 months of HIV infection. Our results suggest a feasible and cost-effective strategy for reversing the HIV epidemic among MSM in China.

Development and Validation of a Personalized Social Media Platform-Based HIV Incidence Risk Assessment Tool for Men Who Have Sex With Men in China.

BACKGROUND: Personalized risk assessments can help medical providers determine targeted populations for counseling and risk reduction interventions. OBJECTIVE: The objective of this study was to develop a social media platform-based HIV risk prediction tool for men who have sex with men (MSM) in China based on an independent MSM cohort to help medical providers determine target populations for counseling and risk reduction treatments. METHODS: A prospective cohort of MSM from Shenyang, China, followed from 2009 to 2016, was used to develop and validate the prediction model. The eligible MSM were randomly assigned to the training and validation dataset, and Cox proportional hazards regression modeling was conducted using predictors for HIV seroconversion selected by the training dataset. Discrimination and calibration were performed, and the related nomogram and social media platform-based HIV risk assessment tool were constructed. RESULTS: The characteristics of the sample between the training dataset and the validation dataset were similar. The risk prediction model identified the following predictors for HIV seroconversion: the main venue used to find male sexual partners, had condomless receptive or insertive anal intercourse, and used rush poppers. The model was well calibrated. The bootstrap C-index was 0.75 (95% CI 0.65-0.85) in the training dataset, and 0.60 (95% CI 0.45-0.74) in the validation dataset. The calibration plots showed good agreement between predicted risk and the actual proportion of no HIV infection in both the training and validation datasets. Nomogram and WeChat-based HIV incidence risk assessment tools for MSM were developed. CONCLUSIONS: This social media platform-based HIV infection risk prediction tool can be distributed easily, improve awareness of personal HIV infection risk, and stratify the MSM population based on HIV risk, thus informing targeted interventions for MSM at greatest risk for HIV infection.

Female and younger subjects have lower adherence in PrEP trials: a meta-analysis with implications for the uptake of PrEP service to prevent HIV.

OBJECTIVE: To estimate the medicine-taking compliance (MTC) level, explore its facilitators and barriers, and quantify the association between MTC level and pre-exposure prophylaxis (PrEP) protective efficacy in individuals at risk of acquiring HIV being administered oral PrEP. DESIGN: Meta-analysis. DATA SOURCES: We searched PubMed, Cochrane and Embase databases for published randomized controlled trials (RCTs) pertaining to MTC of oral PrEP for HIV prevention up to 16 January 2017. REVIEW METHODS: The pooled proportion of MTC and risk ratio (RR) of HIV incidences between intervention group and control group were estimated. RESULTS: We identified 10 eligible studies with 24 193 participants. The overall pooled MTC for oral HIV PrEP was 59.9% (95% CI 43.1% to 74.6%). Subgroup analyses revealed that the MTC level of participants aged <30 years was lower than those equal or older than 30 years (34.9% vs 69.6%, p<0.001); those studies that enrolled only women as participants had lower MTC than those only recruiting either only men or both men and women (31.3% vs 71.7% and 31.3% vs 71.0%, all p<0.01). Additionally, the HIV infection risk increased as the MTC level declines, with the incidence RRs being 0.28 (95% CI 0.19 to 0.41), 0.42 (95% CI 0.29 to 0.62) and 0.75 (95% CI 0.45 to 1.25) in the good (≥80%), moderate (60%~80%) and poor (<60%) MTC subgroups, respectively (linear trend test p<0.01). CONCLUSION: According to the pooled proportion, the MTC of oral HIV PrEP is almost moderate, and its proportion in women and younger participants was relatively low. The protective efficacy of oral PrEP for HIV prevention increased with MTC level. These findings indicated that it is necessary to identify measures to enhance MTC of oral PrEP in future clinical usage, especially in women and younger participants with high HIV infection risk.

HIV Incidence and Care Linkage among MSM First-Time-Testers in Shenyang, China 2012-2014.

HIV testing is the first step to the fulfillment of Treat as Prevention (TasP) and reaching the 90-90-90 goal in HIV control. However, there are still a large number of Men who have Sex with Men (MSM) have never been tested for HIV before, and little is known about the HIV incidence and care linkage among this population. A Mixed method was used to recruit MSM who had never tested for HIV before from January 2012 to December 2014 in Shenyang, China. Potential MSM participants were invited to attend the enrollment for HIV and syphilis testing at a general hospital-based voluntary counseling and test (VCT). HIV confirmed positive subjects were further tested by BED HIV-1 capture enzyme immunoassay (BED-CEIA) to determine the HIV incidence. Syphilis was screened by the rapid plasma reagent test (RPR) and confirmed by Treponema pallidum particle assay (TPPA). All the HIV positive subjects were referred to the local Center for Disease Control and Prevention (CDC) and clinics for HIV primary care and follow-ups. In total 646 HIV first-time-testers of MSM (FMSM) attended this study, 73.4% (474/646) were aged under 31-year-old and 57.3% (370/646) and used the Internet as their major cruising avenue for seeking male sexual partners. The average prevalence of HIV and current syphilis infection was 10.8% (70/646) and 11.0% (71/646), respectively. The HIV incidence was 10.3 (95% confidence interval [CI] 6.1-14.5)/100PY. Multivariate logistic analysis showed that factors such as use of the Internet as the major cruising avenue (adjusted OR [AOR] 2.7, 95% CI 0.9-7.6) and having a current syphilis infection (AOR 4.2, 95% CI 1.8-12.2) were independent correlates of a recent HIV infection. Of the 95 HIV screening test positive FMSM, 73.7% (70/95) returned and be confirmed positive, 92.9% (65/70) of confirmed patients were linked to care. Among those retained and underwent CD4+ T cell test, 76.3% (42/55) started HIV antiretroviral therapy. Among the unconfirmed, 84.0% (21/25) were non-local migrants. The HIV incidence of FMSM in Shenyang was high. Future HIV testing program needs to keep on expanding among the MSM who have never been tested for HIV yet. The Internet-based campaigns and syphilis testing and treatment could represent an opportunity to get access to this hard-to-reach population and link them to HIV care. Future linkage to HIV care of this population should underscore the usage of HIV rapid diagnostic tests to prevent lost at early steps of linkage.

Multi-layered Gag-specific immunodominant responses contribute to improved viral control in the CRF01_AE subtype of HIV-1-infected MSM subjects.

BACKGROUND: The purpose of this study was to characterize specific cytotoxic T-cell (CTL) responses in men who have sex with men (MSM) subjects infected with the human immunodeficiency virus type 1 (HIV-1) CRF01_AE subtype during the first year of infection and impacts on viral control and evolution. RESULTS: Fifteen HIV-1 primary infected cases were recruited from Liaoning MSM prospective cohort. CTL responses to Gag, Pol and Nef proteins at 3 month and 1 year post infection were detected with Gamma interferon enzyme-linked immunospot (ELISPOT) assay using optimized consensus overlapping peptides, as well as the viral quasispecies sequences from the synchronous plasma. Gag and Nef proteins were the main targets of CTL responses during the first year of HIV-1 infection, and this was evident from the data after adjusting for the length of amino acids by dividing the amino acids number of the corresponding protein and multiplying by 100. Additionally, relative magnitudes of Gag at both 3 months and 1 year post infection were significantly negatively correlated with the viral set point (p = 0.002, r = -0.726; p = 0.025, r = -0.574). While the relative magnitude of Nef at 1 year post infection were significantly positively correlated with viral set point (p = 0.004, r = 0.697). Subjects with multi-layered Gag immunodominant responses during the first year of infection had significantly lower viral set points than subjects without such responses (p = 0.002). CONCLUSION: Multi-layered Gag immunodominant responses during the first year of infection were correlated with viral control, which provides a theoretical basis for vaccine design targeting MSM subjects with the CRF01_AE subtype.

Commercial sex and risk of HIV, syphilis, and herpes simplex virus-2 among men who have sex with men in six Chinese cities.

BACKGROUND: Men who have sex with men (MSM) are at high risk of HIV and sexually transmitted infections (STIs) in China and globally. Engaging in commercial sex put them at even greater risk. This study estimated the prevalence of HIV/STIs among three subgroups of MSM: MSM who sold sex (MSM-selling), MSM who bought sex (MSM-buying), and non-commercial MSM (NC-MSM) and evaluated the relationship between commercial sex and HIV/STIs. METHODS: We conducted a cross-sectional survey among MSM in six Chinese cities (Shenyang, Ji'nan, Changsha, Zhengzhou, Nanjing, and Kunming) from 2012 to 2013. Data on socio-demographics and sexual behaviors were collected. Serological tests were conducted to detect HIV, syphilis, and human simplex virus type 2 (HSV-2). RESULTS: Of 3717 MSM, 6.8% were engaged in commercial sex. The overall prevalence of HIV, syphilis and HSV-2 infections was 11.1, 8.8 and 12.1%, respectively. MSM-selling had higher prevalence of HIV (13.4%), syphilis (12.1%) and HSV-2 (17.9%) than NC-MSM (10.9, 8.7 and 11.9% for HIV, syphilis and HSV-2, respectively), though the differences are not statistically significant. Among MSM-selling, HIV prevalence was significantly higher for those who found sex partners via Internet than those did not (19.4% vs. 8.1%, P = 0.04). Compared to NC-MSM, MSM-selling were more likely to use recreation drugs (59.3% vs. 26.3%), have unprotected anal intercourse (77.9% vs. 61.7%), and have ≥10 male sex partners (46.2% vs. 6.2%) in the past 6 months (each P < 0.05). CONCLUSIONS: All three subgroups of MSM in six large Chinese cities have high prevalence of HIV/STIs. Those who sell sex only have a particularly high risk of acquiring and transmitting disease, and therefore, they should be considered as a priority group in HIV/STIs surveillance and intervention programs.