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.

Online distribution of HIV self-testing kits to promote HIV testing among men who have sex with men discontinuing pre-exposure prophylaxis after demonstration project completion in China: a multicentre open-label randomized controlled trial.

Background: HIV self-testing (HIVST) offers potential solutions to challenges associated with site-based HIV testing (SBHT). However, the effectiveness of HIVST as an HIV prevention strategy for men who have sex with men (MSM) discontinuing pre-exposure prophylaxis (PrEP) after the completion of PrEP demonstration project has rarely been assessed. Methods: The China Real-world Study of Oral PrEP (CROPrEP) project was conducted in four cities in China. Participants were directed to community resources to continue their PrEP medication after the discontinuation of project-provided PrEP at the last CROPrEP visit. We conducted a multicentre open-label randomized controlled trial among MSM who had discontinued PrEP induced by the completion of CROPrEP. Eligible participants were randomly assigned to either the intervention group or the control group (1:1). Participants received regular health education and behavioural interventions throughout the trial. The intervention group was given a link to order free HIVST kits online, while the control group received information about free SBHT. Both groups completed internet-based follow-up surveys at three and six months. The primary outcome was the proportion of participants who underwent HIV testing during the six-month follow-up period. This trial was registered at chictr.org.cn (ChiCTR2000038416). Findings: Between November 2020 and January 2021, we recruited a total of 620 participants (300 in the intervention group and 320 in the control group). The follow-up completion rates were 99·0% and 95·0% in the intervention and control groups, respectively. At baseline, the median age of participants was 32 (interquartile range: 26-37), and 77·7% underwent HIV testing in the past three months. The proportion of participants who underwent HIV testing in the past three months was higher in the intervention group than in the control group at both the three-month (adjusted risk difference [RD]: 36·7, 95% confidence interval [CI]: 35·1-38·5, p < 0·001) and six-month (RD: 26·7, 95% CI: 24·6-28·7 p < 0·001) follow-up periods. Interpretation: Our study suggests that providing online distribution of HIVST kits for MSM with PrEP discontinuation induced by completion of the PrEP project effectively promoted HIV testing. This digital approach improves access to HIV testing for MSM and can be applicable to other settings where MSM turn to online public health services. Funding: The study was funded by the Fund of National Natural Science Foundation of China; the Mega-Projects of National Science Research for the 13th Five-Year Plan; and the Liaoning Revitalization Talents Program, China.

Effectiveness and safety of community-led assisted partner service among HIV-diagnosed men who have sex with men: a multicentre, randomized controlled trial in China.

Background: No randomized controlled trials have involved established HIV-diagnosed men who have sex with men (MSM) diagnosed for more than 6 months into the assisted partner service (aPS). We compared voluntary aPS involving community-based organizations (CBOs) and HIV self-testing (aPSST) with regular partner service (rPS) in HIV-diagnosed MSM irrespective of diagnosis time. Methods: In this unblinded, multicentre trial, we enrolled HIV-diagnosed MSM irrespective of diagnosis time in three cities in northern China. Index patients were randomly assigned to aPSST or rPS. Index patients in the aPSST group were additionally provided a comprehensive intervention package including HIV self-testing and CBO-based aPS compared with rPS group. The primary outcome was the number of index patients whose any sexual partner tested for HIV during the 6-month study. Completion of HIV testing was defined as sexual partners taking a clinic-based HIV test or HIV self-testing. Safety was assessed preliminary at the end of the 6-month follow-up. This study has been registered at chictr.org.cn (ChiCTR2000038784). Findings: From March to December 2021, 325 of HIV-diagnosed MSM were enrolled (90⋅2% were established HIV-diagnosed MSM) and randomly assigned to receive aPSST (n = 167) or rPS (n = 158). At 6 months, 110 (65⋅9%) index patients in the aPSST group had at least one sexual partner tested for HIV compared with 50 (31⋅6%) in the rPS group (hazard ratio 2⋅86; 95% confidence interval 2⋅03-4⋅03; p < 0⋅001). No significant difference was observed in effects of aPSST on HIV testing promotion between established and newly HIV-diagnosed MSM. Self-reported harms were infrequently observed in both groups (approximately 2⋅0%). Interpretation: Among HIV-diagnosed MSM regardless of diagnosis time, voluntary aPS involving CBOs and HIV self-testing was effective and safe for promoting partner HIV testing. Funding: This work was supported by the Mega-Projects of National Science Research, the National Natural Science Foundation of China and the Liaoning Revitalization Talents Program, China.

High Human Papillomavirus Vaccine Acceptability and Cost-Effectiveness of the Chinese 2-Valent Vaccine Among Men Who Have Sex With Men: A Cross-Sectional Study in Shenyang, China.

Background: Despite the insupportable burden caused by the human papillomavirus (HPV) and high vaccine acceptability, vaccination programs are not currently available for men who have sex with men (MSM). We aimed to assess HPV infection by examining the willingness for vaccination among MSM and cost-effectiveness of the Chinese 2-valent HPV vaccine. Methods: We recruited MSM in Shenyang, China between July and December 2020 to conduct anal HPV testing and an online survey regarding HPV-related knowledge and vaccine acceptability. We performed a cost-effectiveness analysis to evaluate the incremental cost-effectiveness ratios (ICERs) of the Chinese 2-valent HPV vaccine. Results: A total of 234 participants completed the online survey; of those, 203 were successfully tested for HPV. The median age was 30 years [interquartile range (IQR): 23-38 years]. Most participants had at least undergraduate education (136/234, 58.1%). The acceptability rate for the free HPV vaccine was 57.7% (135/234). The prevalence of HPV types 16 and 18 was 14.9% (18/121) and 26.8% (22/82) in the willing and unwilling to vaccinate groups, respectively (P > 0.05). The prevalence of high-risk HPV among participants aged <30 and ≥50 years was 48.6 and 38.9%, respectively. Using the Chinese per capita gross domestic product (GDP) as a threshold, the Chinese 2-valent HPV vaccine would be a "very cost-effective" strategy, with an ICER value of USD 4,411. This evidence showed that the Chinese 2-valent HPV vaccine was more cost-effective than other imported vaccines. Conclusions: Targeted strategies should be utilized in MSM with different rates of vaccine acceptability. A pilot HPV vaccination program based on the Chinese 2-valent HPV vaccine for MSM is urgently warranted to reduce the burden of HPV and anal cancer.

Prevention and control of HIV/AIDS in China: lessons from the past three decades.

ABSTRACT: In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

Assisted Partner Notification and Uptake of HIV Testing among Men Who Have Sex with Men: A Randomized Controlled Trial in China.

BACKGROUND: Assisted partner notification (PN) is an effective approach for increasing HIV testing among heterosexual partners. There is sparse evidence on its effect among sexual partners of men who have sex with men (MSM). METHODS: A randomized controlled trial was conducted to compare the effect of assisted PN and passive PN interventions on uptake of HIV testing among male and female sexual partners of newly HIV-diagnosed MSM. In the passive PN group, participants were encouraged to disclose their HIV status and refer and persuade sexual partners to access HIV testing services (HTS). In the assisted PN group, participants were further provided with HIV self-testing kits for sexual partners to take a test at home or allow a community health worker from MSM-serving community-based organization (CBO) to anonymously refer and persuade their sexual partners to access HTS. The primary outcome was the proportion of index cases who had any sexual partner accessing HTS within four months after randomization. This trial is registered with chictr.org.cn, ChiCTR1800017813. FINDINGS: Between August 2017 and January 2019, 187 MSM newly diagnosed with HIV in a large city Shenyang in northern China were enrolled in the study and randomly assigned to either passive PN (n=90) or assisted PN (n=97) study groups. The proportion of index cases who disclosed their HIV status to any sexual partners within three months of randomization was similar between passive PN (57%, 95% confidence interval [CI]: 46-67%) and assisted PN groups (58%, 95% CI: 48-68%). During four months of follow-up, the number of sexual partners named, referred to HTS, tested and testing positive per index case was 3•2, 0•7, 0•2 and 0•03 in the passive PN group, and 4•0, 1•0, 0•5 and 0•10 in the assisted PN group. Thirty-five percent of index cases in the assisted PN group had any sexual partners accessing HIV testing compared to 17% in the passive PN group (P = 0•004); 49% sexual partners who were disclosed by index cases in the assisted PN group had access HTS compared to 28% in the passive PN group (P = 0•007). INTERPRETATION: The assisted PN strategy incorporating HIV self-testing and CBO outreach can increase uptake of HIV testing among sexual partners of MSM who were recently diagnosed with HIV. FUNDING: National Science and Technology Major Project of China, National Natural Science Foundation of China, and Project for Overseas Visiting Research of Liaoning Province.

Preference for daily versus on-demand pre-exposure prophylaxis for HIV and correlates among men who have sex with men: the China Real-world Oral PrEP Demonstration study.

INTRODUCTION: This study explores the preference for daily versus on-demand pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in developing countries when both regimens are available. METHODS: From 11 December 2018 to 19 October 2019, we recruited MSM for an open-label real-world PrEP demonstration study in four major cities in China. Subjects selected their preferred PrEP (oral tenofovir/emtricitabine) regimen (daily vs. on-demand) at recruitment and underwent on-site screening before initiation of PrEP. We used logistic regression to assess preference for daily PrEP and correlates. RESULTS: Of 1933 recruited MSM, the median age was 29 years, 7.6% was currently married to or living with a female; the median number of male sexual partners was four and 6.1% had used post-exposure prophylaxis (PEP) in the previous six months. HIV infection risk was subjectively determined as very high (>75%) in 7.0% of subjects, high (50% to 75%) in 13.3%, moderate (25% to 49%) in 31.5% and low or none (0% to 24%) in 48.1%. On average, participants preferred on-demand PrEP over daily PrEP (1104 (57.1%) versus 829 (42.9%)) at recruitment. In multivariable analysis, currently being married to or living with a female was associated with 14.6 percentage points lower preference for daily PrEP (marginal effect = -0.146 [95% CI: -0.230, -0.062], p = 0.001); whereas the number of male sexual partners (marginal effect = 0.003 [95% CI: 0.000, 0.005], p = 0.034) and a subjective assessment of being very high risk of HIV infection (vs. low and no risk, marginal effect size = 0.105 [95% CI: 0.012, 0.198], p = 0.027) were associated with increased preference for daily versus on-demand PrEP. Among the 1933 potential participants, 721 (37.3%) did not attend the subsequent on-site screening. Lower-income, lower education level, lower subjective expected risk of HIV infection risk and younger age positively correlated with the absence of on-site screening. CONCLUSIONS: MSM in China prefer both daily and on-demand PrEP when both regimens are provided free. Social structural factors and subjective risk of HIV infection have significant impacts on PrEP preference and use. The upcoming national PrEP guideline should consider incorporating both regimens and the correlates to help implement PrEP in China.

The use of inappropriate anal douching tool associates with increased HIV infection among men who have sex with men: a cross-sectional study in Shenyang, China.

BACKGROUND: Rectal douching (RD) is widely practiced by men who have sex with men (MSM), and is associated with increased risk of HIV infection. However, the mechanism of how RD increases the risk of HIV infection is not well understood, and there is limited data on RD behavior in MSM practicing anal sex in China. We examine the purpose of RD, its timing in relation to anal sex, the types of RD products used, and risky sexual behaviors among MSM reporting anal sex. METHODS: Between August 2017 and December 2018, a cross-sectional study was conducted among adult MSM in Shenyang, China. Data were collected on demographics, sexual behaviors, and RD for the most recent sexual intercourse by means of interviewer-administered face-to-face questionnaires. Blood samples were collected to test for antibodies to HIV and syphilis. Multivariable logistic regression models were used to assess the risk factors associated with HIV infection. RESULTS: A total of 515 eligible MSM participated in this survey (median age: 31 years). During the most recent anal intercourse, 28.3% (146/515) had condomless receptive anal intercourse (CRAI), 21.4% (110/515) practiced serosorting, and more than half (61.6%, 317/515) reported RD before or after anal sex. Of those practicing RD, 96.8% (307/317) conducted RD before sex, while 62.5% (198/317) conducted RD after sex. The douching devices used were primarily shower hoses (85.3%, 262/307), and relatively few MSM used commercial RD products (8.1%, 25/307) before sex. The prevalence of HIV-1 and syphilis was 11.7% and 13.2%, respectively. HIV infection was positively associated with RD, practicing RD before sex, the interaction between RD and CRAI using a shower hose for RD and other risk factors, practicing RD after sex, CRAI, using nitrite inhalants, main sexual role with males as bottom and syphilis infection. CONCLUSIONS: RD is popular among Chinese MSM. Improper noncommercial RD tools use (such as shower hose), the interaction effect between RD and CRAI associated with HIV infection. Public health workers and the MSM community should publicize scientific knowledge and prevention approaches relating to RD and HIV transmission to MSM. We recommend that further studies should be conducted to understand the detailed mechanism between RD and increased HIV prevalence.

Disparity of human immunodeficiency virus incidence and drug resistance in college student, non-student youth and older men who have sex with men: a cross-sectional study from seven major cities of China.

BACKGROUND: Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM. METHODS: We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤ 168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, <25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance. RESULTS: Overall, 4,496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1,094 NSYM, and 2,837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100PY, 12.9 (95% CI: 9.8-16.1)/100PY, 6.8 (95% CI: 5.4-8.2)/100PY, and TDR prevalence were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age< 21-year-old, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (AOR: 2.5; 95% CI: 1.0-5.8). CONCLUSIONS: College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.

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.

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.

Intimate Partner Violence Correlates With A Higher HIV Incidence Among MSM: A 12-Month Prospective Cohort Study in Shenyang, China.

Intimate partner violence (IPV) and HIV are highly prevalent worldwide among MSM. However, the association between IPV and HIV seroconversion is virtually unknown. This 12-month prospective cohort study was conducted among MSM in Shenyang, China to explore the causality between IPV and the incidence of HIV. Adjusted Hazard Ratios (aHRs) of HIV acquisition were derived from a multivariate time-dependent Cox model and applied to calculate population attributable fractions (PAFs). Among 476 HIV-negative MSM subjects, 89(18.7%) reported being victims of IPV in the past 3 months (P3M). IPV was significantly correlated with lower education, having more condomless anal intercourse (CAI) and being depressed (each P < 0.05). The incidence of HIV among IPV victims was 11.3/100 PY compared to 3.8/100 PY in non-IPV-victims. Furthermore, IPV victimization was independently associated with HIV seroconversion (aHR = 4.1, PAF = 37.9%). Other predictors for seroconversion included non-local residence in Liaoning province (aHR = 3.9, PAF = 45.2%), engaging in condomless receptive anal intercourse (CRAI)(aHR = 3.1, PAF = 24.2%) or CAI with casual male partners (aHR = 3.8, PAF = 26.3%) in the P3M and syphilis infection (aHR = 4.7, PAF = 33.7%) (each P < 0.05). IPV increased the HIV seroconversion risk of MSM, with a high PAF. HIV prevention programs should integrate IPV screening and intervention, and MSM affected by IPV need to be preferentially enrolled in pre-exposure prophylaxis.

Poppers use and Sexual Partner Concurrency Increase the HIV Incidence of MSM: a 24-month Prospective Cohort Survey in Shenyang, China.

The use of poppers is highly prevalent in MSM, but little is known about the association between their use and HIV incidence in China. A prospective cohort study was conducted from 2011 to 2013 in MSM in Shenyang. 475(79.6%) of eligible HIV-negative MSM participated in this prospective survey and near one fourth MSM (23.4%) ever used poppers. About one-third of the participants had condomless anal intercourse, half had multiple sexual partners and 10.5% were syphilis positive. The HIV incidence densities were15.5 (95% CI:9.4-23.4)/100 PY[person-years]) and 4.6 (95% CI:2.9-7.0)/100 PY in poppers-users and non-poppers-users, respectively. Predictors of HIV seroconversion included poppers-using-behavior, having had more than two male partners, practicing group sex, unprotected anal intercourse(UAI) with male partners, and baseline syphilis positivity (all P < 0.05). In conclusion, the use of poppers, high-risk-sexual behaviors and syphilis infection significantly increase the HIV incidence among Shenyang MSM. It is essential for policy makers to add poppers to the official controlled illicit drug list to reduce HIV transmission among the MSM community. A comprehensive strategy should also be implemented to control both their high-risk-sexual behaviors and risk of syphilis infection, since these may represent novel ways to prevent new HIV infections in these MSM.

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.

Deregulated MicroRNA-21 Expression in Monocytes from HIV-Infected Patients Contributes to Elevated IP-10 Secretion in HIV Infection.

Persistent activation and inflammation impair immune response and trigger disease progression in HIV infection. Emerging evidence supports the supposition that excessive production of interferon-inducible protein 10 (IP-10), a critical inflammatory cytokine, leads to immune dysfunction and disease progression in HIV infection. In this study, we sought to elucidate the cause of the upregulated production of IP-10 in HIV infection and explore the underlying mechanisms. Bolstering miR-21 levels using mimics resulted in the obvious suppression of lipopolysaccharide (LPS)-induced IP-10 in monocyte leukemia cells THP-1 and vice versa. The analysis of the primary monocytes of HIV patients revealed significantly less miR-21 than in healthy controls; this was opposite to the tendency of IP-10 levels in plasma. The secretion of IP-10 due to LPS stimulation was not affected by miR-21 modulation in the differentiated THP-1 macrophages (THP-1-MA). We found a novel switch, IFN-stimulated gene 15 (ISG15), which triggers the expression of IP-10 and is significantly upregulated during the differentiation of THP-1 into THP-1-MA. The inhibition of ISG15 can restore the regulation of IP-10 by miR-21. In summary, IP-10 expression in monocytes is regulated by miR-21, whereas in macrophages, this fine-tuning is attenuated by the enhanced expression of ISG15. This study paves the way to a comprehensive understanding of the molecular regulatory mechanism of IP-10, a key point in immune intervention strategy.

Myeloid-Derived Suppressor Cells Associated With Disease Progression in Primary HIV Infection: PD-L1 Blockade Attenuates Inhibition.

OBJECTIVE: Events occurring during the initial phase of human immunodeficiency virus (HIV) infection are intriguing because of their dramatic impact on the subsequent course of the disease. In particular, the relationship between myeloid-derived suppressor cells (MDSCs) and HIV pathogenesis in primary infection remains unknown and the mechanism of MDSCs in HIV infection are incompletely defined. METHODS: The frequency of MDSC expression in patients with primary HIV infection (PHI) and chronic HIV infection was measured, and the association with disease progression was studied. Programmed death-ligand 1 (PD-L1) and galectin-9 (Gal-9) expression on MDSCs was measured and in vitro blocking experiments were performed to study the role of PD-L1 in MDSCs' inhibition. RESULTS: We found increased levels of HLA-DRCD14CD33CD11b granulocytic(G)-MDSCs in PHI individuals compared with normal controls, which correlated with viral loads and was negatively related to CD4 T-cell levels. When cocultured with purified G-MDSCs, both proliferation and interferon-γ secretion by T cell receptor (TCR)-stimulated CD8 T cells from HIV-infected patients were significantly inhibited. We also demonstrated that PD-L1, but not Gal-9, expression on HLA-DRCD14CD33CD11b cells increased during HIV infection. The suppressive activity of G-MDSCs from HIV-infected patients was attenuated by PD-L1 blockade. CONCLUSIONS: We found a significant increase in G-MDSCs in PHI patients that was related to disease progression and PD-L1 was used by MDSCs to inhibit CD8 T cells in HIV infection. Our data improve the understanding of HIV pathogenesis in PHI.

Prevalence and Determinants of Herpes Simplex Virus Type 2 (HSV-2)/Syphilis Co-Infection and HSV-2 Mono-Infection among Human Immunodeficiency Virus Positive Men Who Have Sex with Men: a Cross-Sectional Study in Northeast China.

This study assessed the prevalence and determinants of herpes simplex virus type 2 (HSV-2)/syphilis co-infection and HSV-2 mono-infection in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) in China. A cross-sectional study was conducted of 545 HIV-positive MSM in Shenyang between February 2009 and October 2014. Participants underwent physical examinations and serological tests for HSV-2 and syphilis. A multinomial logistic regression was used to identify the risk factors associated with HSV-2/syphilis co-infection and HSV-2 mono-infection. The prevalence of HSV-2 mono-infection, syphilis mono-infection, and HSV-2/syphilis co-infection (95% confidence interval) was 48.6% (44.4-52.8%), 34.3% (30.3-38.3%), and 22.9% (19.4-26.5%), respectively. After controlling within HSV-2/syphilis-seropositive cases, regression analysis revealed that the related factors for HSV-2/syphilis co-infection included age (25-50 vs. ≤ 24 years: adjusted odds ratio [aOR], 4.55; > 50 vs. ≤ 24 years: aOR, 43.02), having regular female sexual partner(s) in the past 6 months (aOR, 0.43), and age at first MSM experience (≤ 18 vs. > 18 years: aOR, 2.59) (all P < 0.05). The high prevalence of HSV-2 mono infection and HSV-2/syphilis co-infection in HIV-positive MSM indicates a high secondary HIV transmission risk. A campaign for detection and treatment of HSV-2 and syphilis is urgently required for HIV-positive MSM in China.

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.

Internet-Based Sex-Seeking Behavior Promotes HIV Infection Risk: A 6-Year Serial Cross-Sectional Survey to MSM in Shenyang, China.

HIV prevalence is still rapidly increasing among Chinese men who have sex with men (MSM). The Internet also makes it easier for MSM to have casual partners. This study aims to evaluate the trend of Internet-based sex-seeking behavior of MSM and its impact on HIV prevalence, the distribution of HIV subtype strains, and transmitted drug resistance rates. A serial cross-sectional study was conducted from 2009 to 2014. Of the 1,981 MSM, 50.5% (1,000/1,981) mainly sought homosexual partners through the Internet (Internet-based MSM, IBM). The proportion of IBM among total MSM subjects increased from 43.3% to 61.5% (p < 0.001). HIV prevalence of IBM increased from 5.7% to 20.7%, while that of non-Internet-based MSM (NIBM) increased from 7.0% to 14.7%. A relative higher proportion of NIBM were infected with HIV CRF01_AE subtype than IBM (79.5% versus 72.2%, p = 0.52). Multivariable analysis found IBM had a significantly higher HIV prevalence than NIBM (13.2% versus 10.5%, aOR = 1.4, 95% CI [1.0-1.9]). Being a migrant non-Shenyang resident MSM (aOR = 1.9, 95% CI [1.3-2.9]) and occasionally/never using condoms with casual homosexual partners (aOR = 1.7, 95% CI [1.1-2.6]) were two distinct risk factors for HIV infection in IBM. More efforts should be targeted towards developing interventions aimed at IBM, particularly migrant MSM and who engage in UAI with casual homosexual partners.