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.

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.

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.

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.

Undiagnosed HIV Infections May Drive HIV Transmission in the Era of "Treat All": A Deep-Sampling Molecular Network Study in Northeast China during 2016 to 2019.

Universal antiretroviral therapy (ART, "treat all") was recommended by the World Health Organization in 2015; however, HIV-1 transmission is still ongoing. This study characterizes the drivers of HIV transmission in the "treat all" era. Demographic and clinical information and HIV pol gene were collected from all newly diagnosed cases in Shenyang, the largest city in Northeast China, during 2016 to 2019. Molecular networks were constructed based on genetic distance and logistic regression analysis was used to assess potential transmission source characteristics. The cumulative ART coverage in Shenyang increased significantly from 77.0% (485/630) in 2016 to 93.0% (2598/2794) in 2019 (p < 0.001). Molecular networks showed that recent HIV infections linked to untreated individuals decreased from 61.6% in 2017 to 28.9% in 2019, while linking to individuals with viral suppression (VS) increased from 9.0% to 49.0% during the same time frame (p < 0.001). Undiagnosed people living with HIV (PLWH) hidden behind the links between index cases and individuals with VS were likely to be male, younger than 25 years of age, with Manchu nationality (p < 0.05). HIV transmission has declined significantly in the era of "treat all". Undiagnosed PLWH may drive HIV transmission and should be the target for early detection and intervention.

Antiretroviral therapy initiation within 7 and 8-30 days post-HIV diagnosis demonstrates similar benefits in resource-limited settings.

We estimated the optimum time to initiate antiretroviral therapy (ART) in a retrospective observational cohort. We observed that ART initiation 7 days or less ( n  = 817) and 8-30 days ( n  = 1009) were the most important factors with viral suppression, and had similar viral suppression rate, CD4 + T-cell count increase and fractions of individuals with links at least 4 and individuals linked to recent HIV infection in HIV molecular networks. This study provides real-world evidence on the benefits of rapid ART initiation in resource-limited setting.

Medication Non-adherence and Condomless Anal Intercourse Increased Substantially During the COVID-19 Pandemic Among MSM PrEP Users: A Retrospective Cohort Study in Four Chinese Metropolises.

Background: The coronavirus disease (COVID-19) pandemic has impacted HIV prevention strategies globally. However, changes in pre-exposure prophylaxis (PrEP) adherence and HIV-related behaviors, and their associations with medication adherence among men who have sex with men (MSM) PrEP users remain unclear since the onset of the COVID-19 pandemic. Methods: A Retrospective Cohort Study of HIV-negative MSM PrEP users was conducted in four Chinese metropolises from December 2018 to March 2020, assessing the changes in PrEP adherence and HIV-related behaviors before and during the COVID-19. The primary outcome was poor PrEP adherence determined from self-reported missing at least one PrEP dose in the previous month. We used multivariable logistic regression to determine factors correlated with poor adherence during COVID-19. Results: We enrolled 791 eligible participants (418 [52.8%] in daily PrEP and 373 [47.2%] in event-driven PrEP). Compared with the data conducted before the COVID-19, the proportion of PrEP users decreased from 97.9 to 64.3%, and the proportion of poor PrEP adherence increased from 23.6 to 50.1% during the COVID-19 [odds ratio (OR) 3.24, 95% confidence interval (CI) 2.62-4.02]. While the percentage of condomless anal intercourse (CAI) with regular partners (11.8 vs. 25.7%) and with casual partners (4.4 vs. 9.0%) both significantly increased. The proportion of those who were tested for HIV decreased from 50.1 to 25.9%. Factors correlated with poor PrEP adherence during the COVID-19 included not being tested for HIV (adjusted odds ratio [aOR] = 1.38 [95% CI: 1.00, 1.91]), using condoms consistently with regular partners (vs. never, aOR = 2.19 [95% CI: 1.16, 4.13]), and being married or cohabitating with a woman (vs. not married, aOR = 3.08 [95% CI: 1.60, 5.95]). Conclusions: Increased poor PrEP adherence and CAI along with the decrease in HIV testing can lead to an increase in HIV acquisition and drug resistance to PrEP. Targeted interventions are needed to improve PrEP adherence and HIV prevention strategies.

Association of HIV Preexposure Prophylaxis Use With HIV Incidence Among Men Who Have Sex With Men in China: A Nonrandomized Controlled Trial.

Importance: Evidence on HIV preexposure prophylaxis (PrEP) among Chinese men who have sex with men (MSM) is critical to guide its large-scale implementation in low- and middle-income countries. Objective: To evaluate incident HIV infection, adherence, safety, and changes in sexual behaviors among MSM using daily PrEP (D-PrEP) and event-driven PrEP (ED-PrEP) in 4 cities in China. Design, Setting, and Participants: This nonrandomized controlled trial was conducted among HIV-seronegative MSM from December 11, 2018, to November 30, 2020, in Beijing, Shenyang, Chongqing, and Shenzhen. Participants self-chose D-PrEP or ED-PrEP regimens at baseline and could switch regimens during the 12-month study period. HIV-negative MSM who declined to initiate PrEP (nonusers) in the same cities joined a separate parallel prospective cohort and served as control individuals. Interventions: PrEP consisted of coformulated tenofovir disoproxil fumarate, 300 mg, and emtricitabine, 200 mg. Main Outcomes and Measures: The main outcome was incident HIV infection. Poisson regression was used to obtain the HIV incidence rate ratio (IRR). Results: A total of 1530 MSM were included in the analysis (median age, 30 [IQR, 25-37] years). At baseline, 520 MSM chose D-PrEP (median age, 29 [IQR, 25-35] years) and 503 chose ED-PrEP (median age, 29 [IQR, 25-36] years). The median HIV Risk Index score was 18 (IQR, 12-22) among D-PrEP users and 18 (IQR, 11-22) among ED-PrEP users. Among 507 PrEP nonusers, the median age was 33 (IQR, 27-43) years, and the median HIV Risk Index score was 12 (IQR, 7-18). Although PrEP users had more baseline behaviors associated with HIV risk, the HIV incidence was lower among all PrEP users (adjusted IRR, 0.09 [95% CI, 0.04-0.21]), ED-PrEP users (adjusted IRR, 0.05 [95% CI, 0.01-0.22]), and D-PrEP users (adjusted IRR, 0.12 [95% CI, 0.04-0.33]) compared with PrEP nonusers. There was no difference in HIV incidence between D-PrEP users and ED-PrEP users (IRR, 0.33 [95% CI, 0.06-2.04]). Event-driven PrEP users consumed 40% fewer tablets than D-PrEP users during the study period. Adherence, defined as the proportion of self-reported days with sexual intercourse in which PrEP was taken according to prescription of at least 90%, increased over time among ED-PrEP users (from 57.4% to 77.8%; P < .001 for trend) and decreased over time among D-PrEP users (from 75.1% to 72.1%; P = .02 for trend). Daily PrEP users reported fewer adverse events than ED-PrEP users (193 of 520 [37.1%] vs 241 of 503 [47.9%]). Conclusions and Relevance: The findings of this study suggest that D-PrEP and ED-PrEP regimens are associated with lower incidence of HIV and a good safety profile among high-risk MSM in China. Trial Registration: Chinese Clinical Trial Registry number: ChiCTR-IIN-17013762.

Remnant Lipoprotein Cholesterol as a Factor Related to Adult Fatty Liver Disease.

CONTEXT: Dyslipidemia is related to fatty liver disease (FLD), whose relationship with remnant lipoprotein cholesterol (RLP-C), a component of blood lipids, remains unclear. OBJECTIVE: To clarify the correlation between RLP-C and the occurrence and severity of FLD and establish an FLD discriminant model based on health check indicators. METHODS: Retrospective study of participants who underwent health check-up in the First Affiliated Hospital of China Medical University (Shenyang, China) between January and December 2019. We categorized participants according to liver ultrasound results and analyzed the correlation between RLP-C and occurrence of FLD (n = 38 885) through logistic regression, restricted cubic spline, and receiver operating characteristic curve. We categorized the severity of FLD according to the control attenuation parameter and analyzed the correlation between RLP-C and FLD severity through multiple logistic regression; only males were included (n = 564). RESULTS: The adjusted OR (aOR) per SD between RLP-C and FLD was 2.33 (95% CI 2.21-2.46, P < .001), indicating a dose-response relationship (P < .0001). The optimal cut-off value of RLP-C was 0.45 mmol/L and the area under the curve (AUC) was 0.79. The AUC of the 8-variable model was 0.89 in both the training and the validation sets. FLD severity was related to the level of RLP-C (aOR per SD = 1.29, 95% CI 1.07-1.55, P = .008). CONCLUSION: RLP-C has a strong positive correlation with FLD occurrence and FLD severity. These results may help clinicians identify and implement interventions in individuals with high FLD risk and reduce FLD prevalence.

The Viral Founder Effect and Economic-Driven Human Mobility Shaped the Distinct Epidemic Pattern of HIV-1 CRF01_AE in Northeast China.

Background: In China, two distinct lineages shaped the epidemic of HIV-1 CRF01_AE among men who have sex with men (MSM), of which the uneven distributions were observed geographically. One lineage spread across China, while another dominated in Northeast China. Understanding the drivers of viral diffusion would provide guidelines for identifying the source and hotspots of HIV transmission among MSM to target interventions in China. Methods: We collected the pol sequences between 2002-2017 to reconstruct the spatiotemporal history of CRF01_AE lineages in Shenyang, one economic center of Northeast China, using the Bayesian phylogeographic and phylodynamic approaches. Importantly, for the datasets with the high sample density, we did the down-sampling to avoid the sampling bias. Results: Two lineages accounted for 97%, including 426 and 1516 sequences, and homosexuals and bisexuals were above 80%. One lineage appeared earlier 7 years than another (1993 vs. 2002) among homosexuals and bisexuals, whereas among heterosexuals, both lineages were observed firstly in 2002. 96% viral migrations within one lineage were from homosexuals toward bisexuals (49%) and male-heterosexuals (46%). Within another, except for homosexuals (72%), bisexuals (23%) served as the top second source, and female-heterosexuals (11%) were the third recipients following bisexuals (44%) and male-heterosexuals (39%). Although the basic reproduction number (R0) of two lineages were similar and both of the effective production number (Re) fell below 1 at the most recent sampling time, the starts of the Re declining varied. Conclusions: Our findings revealed that throughout the viral national spread chain, Shenyang is the source for the initial expanding of one lineage, where is only a sink of another, proving that the viral founder effect and regional human mobility contributed to the uneven distribution of two lineages, and emphasizing the important roles of the area where the virus originated and economy-driven migrants in HIV transmission.

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.

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.

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.

IP-10 Promotes Latent HIV Infection in Resting Memory CD4+ T Cells via LIMK-Cofilin Pathway.

A major barrier to HIV eradication is the persistence of viral reservoirs. Resting CD4+ T cells are thought to be one of the major viral reservoirs, However, the underlying mechanism regulating HIV infection and the establishment of viral reservoir in T cells remain poorly understood. We have investigated the role of IP-10 in the establishment of HIV reservoirs in CD4+ T cells, and found that in HIV-infected individuals, plasma IP-10 was elevated, and positively correlated with HIV viral load and viral reservoir size. In addition, we found that binding of IP-10 to CXCR3 enhanced HIV latent infection of resting CD4+ T cells in vitro. Mechanistically, IP-10 stimulation promoted cofilin activity and actin dynamics, facilitating HIV entry and DNA integration. Moreover, treatment of resting CD4+ T cells with a LIM kinase inhibitor R10015 blocked cofilin phosphorylation and abrogated IP-10-mediated enhancement of HIV latent infection. These results suggest that IP-10 is a critical factor involved in HIV latent infection, and that therapeutic targeting of IP-10 may be a potential strategy for inhibiting HIV latent infection.

Rapid Clinical Progression and Its Correlates Among Acute HIV Infected Men Who Have Sex With Men in China： Findings From a 5-Year Multicenter Prospective Cohort Study.

Background: In the "treat all" era, there are few data on the nature of HIV clinical progression in middle-income countries. The aim of the current study was to prospectively analyze the clinical progression of HIV and its indicators among men in China with acute HIV who have sex with men. Methods: From 2009-2014 a total of 400 men with acute HIV infection (AHI) were identified among 7,893 men who have sex with men via periodic pooled nucleic acid amplification testing, and they were assigned to an AHI prospective cohort in Beijing and Shenyang, China. Rapid progression was defined as two consecutive CD4+ T cell counts < 350/µL within 3-24 months post-infection. Kaplan-Meier and Cox-regression analyses were conducted to identify predictors of rapid progression. Results: Among 400 men with AHI 46.5% were rapid progressors, 35.1% reached rapid progressor status by 12 months post-infection, and 63.9% reached rapid progressor status by 24 months. Rapid progression was associated with herpes simplex-2 virus coinfection (adjusted hazard ratio [aHR] 1.7, 95% confidence interval [CI] 1.2-2.3], depression (aHR 1.9, 95% CI 1.5-2.6), baseline CD4+ T cell count < 500/µL (aHR 3.5, 95% CI 2.4-5.1), higher baseline HIV viral load (aHR 1.6, 95% CI 1.2-2.3), acute symptoms lasting ≥ 2 weeks (aHR 1.6, 95% CI 1.1-2.2), higher body mass index (aHR 0.9, 95% CI 0.9-1.0), higher HIV viral load (aHR 1.7, 95% CI 1.4-2.1), set point viral load at 3 months (aHR 2.0, 95% CI 1.6-2.5), each 100-cell/µL decrease in CD4+ T cell count at 3 months (aHR 2.2, 95% CI 1.9-2.5), and baseline routine blood tests including white blood cell count < 5.32, hemoglobin ≥ 151, mean corpuscular hemoglobin ≥ 30.5, hemoglobin concentration ≥ 342, mean platelet count ≥ 342, lymphocytes ≥ 1.98, and mixed cell count ≥ 0.4 (all p < 0.05). Conclusion: Almost half of the patients underwent rapid clinical progression within 2 years after HIV infection. A treat-all policy is necessary and should be strengthened globally. Rapid progression was correlated with herpes simplex-2 virus coinfection, depression, low CD4+ T cell counts, and high set point viral load in acute infection stage. Rapid progression can be identified via simple indicators such as body mass index and routine blood test parameters in low and middle-income countries.

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.