Riemerella anatipestifer UvrC is required for iron utilization, biofilm formation and virulence.

UvrC is a subunit of excinuclease ABC, which mediates nucleotide excision repair (NER) in bacteria. Our previous studies showed that transposon Tn4531 insertion in the UvrC encoding gene Riean_1413 results in reduced biofilm formation by Riemerella anatipestifer strain CH3 and attenuates virulence of strain YZb1. In this study, whether R. anatipestifer UvrC has some biological functions other than NER was investigated. Firstly, the uvrC of R. anatipestifer strain Yb2 was in-frame deleted by homologous recombination, generating deletion mutant ΔuvrC, and its complemented strain cΔuvrC was constructed based on Escherichia coli - R. anatipestifer shuttle plasmid pRES. Compared to the wild-type (WT) R. anatipestifer strain Yb2, uvrC deleted mutant ΔuvrC significantly reduced biofilm formation, tolerance to H2O2- and HOCl-induced oxidative stress, iron utilization, and adhesion to and invasion of duck embryonic hepatocytes, but not its growth curve and proteolytic activity. In addition, animal experiments showed that the LD50 value of ΔuvrC in ducklings was about 13-fold higher than that of the WT, and the bacterial loads in ΔuvrC infected ducklings were significantly lower than those in Yb2-infected ducklings, indicating uvrC deletion in R. anatipestifer attenuated virulence. Taken together, the results of this study indicate that R. anatipestifer UvrC is required for iron utilization, biofilm formation, oxidative stress tolerance and virulence of strain Yb2, demonstrating multiple functions of UvrC.RESEARCH HIGHLIGHTSDeletion of uvrC in R. anatipestfer Yb2 significantly reduced its biofilm formation.uvrC deletion led to reduced tolerance to H2O2- and HOCl-induced oxidative stress.The iron utilization of uvrC deleted mutant was significantly reduced.The uvrC deletion in R. anatipestifer Yb2 attenuated its virulence.

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.

DEAD Box Protein DhR1 Is a Global Regulator Involved in the Bacterial Fitness and Virulence of Riemerella anatipestifer.

DEAD box proteins perform diverse cellular functions in bacteria. Our group previously reported that the transposon Tn4531 insertion in Riean_0395 (designated dhR1), which encodes a putative DEAD box helicase, attenuated the virulence of R. anatipestifer strain YZb1. Here, we show that, compared to the wild-type (WT) R. anatipestifer strain Yb2, the growth or survival of the ΔdhR1 mutant in tryptic soy broth (TSB) was significantly decreased in response to cold, pH, osmotic stress, ethanol, Triton X-100, and oxidative stress, and the dhR1 deletion significantly reduced biofilm formation and the adhesion capacity to Vero cells, whereas the growth of ΔdhR1 was less impaired in iron-limited TSB. Moreover, the virulence of ΔdhR1 in ducklings was attenuated by about 80-fold, compared to the WT. In addition, a transcriptome analysis showed that the dhR1 deletion in the strain Yb2 affected the expression of 58 upregulated genes and 98 downregulated genes that are responsible for various functions. Overall, our work reveals that the deletion of DhR1 results in a broad effect on the bacterial fitness, biofilm formation, iron utilization, and virulence of R. anatipestifer, which makes it a global regulator. IMPORTANCE R. anatipestifer infection has been a continued and serious problem in many duck farms, but little is known about the mechanism underlying the pathogenesis of R. anatipestifer and how R. anatipestifer adapts to the external environment and thereby persists in duck farms. The results of this study demonstrate that the DEAD box protein DhR1 is required for the tolerance of R. anatipestifer to cold, pH, and other stresses, and it is also necessary for biofilm formation, iron utilization, and virulence in ducklings, demonstrating multiple functions of DhR1.

Inhibitory receptor CD47 binding to plasma TSP1 suppresses NK-cell IFN-γ production via activating the JAK/STAT3 pathway during HIV infection.

BACKGROUND: Natural killer (NK) cells play an important first-line role against tumour and viral infections and are regulated by inhibitory receptor expression. Among these inhibitory receptors, the expression, function, and mechanism of cluster of differentiation 47 (CD47) on NK cells during human immunodeficiency virus (HIV) infection remain unclear. METHODS: Fresh peripheral blood mononuclear cells (PBMCs) were collected from people living with HIV (PLWH) and HIV negative controls (NC) subjects. Soluble ligand expression levels of CD47 were measured using ELISA. HIV viral proteins or Toll-like receptor 7/8 (TLR7/8) agonist was used to investigate the mechanisms underlying the upregulation of CD47 expression. The effect of CD47 on NK cell activation, proliferation, and function were evaluated by flow cytometry. RNA-seq was used to identify downstream pathways for CD47 and its ligand interactions. A small molecule inhibitor was used to restore the inhibition of NK cell function by CD47 signalling. RESULTS: CD47 expression was highly upregulated on the NK cells from PLWH, which could be due to activation of the Toll-like receptor 7/8 (TLR7/8) pathway. Compared with NC subjects, PLWH subjects exhibited elevated levels of CD47 ligands, thrombospondin-1 (TSP1), and counter ligand signal regulatory protein-α (SIRPα). The TSP1-CD47 axis drives the suppression of interferon gamma (IFN-γ) production and the activation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway in NK cells. After treatment with a STAT3 inhibitor, the NK cells from PLWH showed significantly improved IFN-γ production. CONCLUSIONS: The current data indicate that the binding of the inhibitory receptor CD47 to plasma TSP1 suppresses NK cell IFN-γ production by activating the JAK/STAT3 pathway during HIV infection. Our results suggest that CD47 and its related signalling pathways could be targets for improving NK cell function in people living with HIV.

Impact of different industrial activities on heavy metals in floodplain soil and ecological risk assessment based on bioavailability: A case study from the Middle Yellow River Basin, northern China.

Understanding the impact of different industrial activities on heavy metals and conducting scientific ecological risk assessments are critical to the management of heavy metal pollution. The present study compared soils affected by different industrial activities in three types of industrial cities (coal city, oil-gas city, and economic city) to control samples and examined the ecological risk based on bioavailability in the Middle Yellow River Basin. The findings revealed that the impact characteristics of different industrial activities on soil heavy metals in the research area were different. Both coal-based and oil-gas industry activities had a minor impact on soil heavy metals, whereas economic industry activities in the southern part had a major impact, as evidenced by significant enrichment of Cd, Hg, Cu, Pb, and Zn. In principal component analysis, the soil heavy metals affected by economic industry activities designated a distinct source from the control samples, particularly the anthropogenic sources represented by Hg and Cd. In the context of heavy metals in chemical form, three types of industrial activities all had an effect on bioavailability (0.72-24.27%) and could increase migratory activity in the environment. Furthermore, both traditional and improved assessments, based on total content and bioavailability, showed a low ecological risk near coal cities and oil-gas cities in the middle and northern parts, while there was a medium-high ecological risk near economically developed cities in the south, particularly Tianshui, Baoji, Qishan, Xianyang, Xi'an, and Tongchuan. In comparison, improved risk assessment based on bioavailability tends to not only compensate for an overestimation in traditional risk assessment from the perspective of total content, but additionally achieve a more reasonable, effective, and advanced assessment of heavy metal risks in scientific research. The outcome of this study has significance for the ecological conservation and high-quality development of the Yellow River Basin.

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.

Identification of genetic determinants of hemolytic activity of Riemerella anatipestifer using random transposon mutagenesis.

Riemerella anatipestifer causes epizootic infectious disease in poultry resulting in serious economic losses especially to the duck industry. In our previous study, R. anatipestifer was found to lyse duck erythrocytes in vitro. In the present study, a random Tn4351 mutagenesis library of hemolytic R. anatipestifer strain SX containing 4000 mutants was constructed to investigate the genetic basis of hemolytic activity. Thirty mutants with reduced hemolytic activity and one with increased hemolytic activity were screened and insertions in 24 genes were identified. Of these genes, four were predicted to encode outer membrane proteins, one encoded a cytoplasmic membrane protein, 11 encoded cytoplasmic proteins, and eight encoded proteins with unknown locations. Based on current annotations of the R. anatipestifer genomes, of the 24 genes, 7 (29.17%) were involved in iron utilization. The hemolytic activities of the complemented strains M2 (pRES-Riean_0790) and M18 (pRES-Riean_0653) were restored, indicating that both Riean_0653 and Riean_0790 are involved in the hemolytic activity of strain SX. However, the recombinant proteins rRiean_0317, rRiean_0790, rRiean_0653, rRiean_1027, rRiean_1143, and rRiean_1561 had no hemolytic activity, suggesting that none were hemolysins.

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.

Use of multiple recreational drugs is associated with new HIV infections among men who have sex with men in China: a multicenter cross-sectional survey.

BACKGROUND: There is limited information about the types of recreational drugs used by men who have sex with men (MSM) in China or the consequent impact on sexual health and human immunodeficiency virus (HIV) acquisition. METHODS: We recruited MSM from seven cities in China between 2012 and 2013 using multiple approaches including advertisements on gay websites, collaborating with local MSM community-based organizations, peer referrals, and venues such as gay bars and bathrooms visited by MSM. We divided participants into four subgroups based on the number of recreational drugs (RDs) used in the previous 6 months. We defined use of multiple RDs as use of ≥2 types of RDs. Demographics and HIV-related high-risk behaviors were collected, and blood samples were tested for recent HIV infection by the HIV-1 subtypes B, E, and D immunoglobulin G capture enzyme immunoassay (BED-CEIA). We used multivariable logistic regression adjusted for sociodemographics to determine the adjusted odds ratios (aORs) and associated 95% confidence intervals (CIs) of the subgroups of RD use for recent or established HIV infection. RESULTS: A total of 4496 Chinese MSM participated; 28.4% used RDs, and 5% used multiple types of RDs. The prevalence of each RD use was as follows: poppers (25.9%), ecstasy (2.4%), ketamine (1.2%), amphetamine (0.6%), tramadol (0.4%), methamphetamine (3.8%), and codeine (1.9%). Users of multiple RDs commonly used poppers combined with one or more other types of RDs. Multiple RD users were likely to be aged 26-30 years (vs. 18-25 and > 30 years), live in non-local cities (vs. local cities), never married (vs. married), have a high monthly income (vs. no income and 1-599 USD), use versatile positions during anal intercourse (vs. top or bottom), and have inadequate HIV-related prevention knowledge (vs. adequate). As the number of RDs used in the previous 6 months increased, the prevalence of HIV-related high-risk behaviors increased (P < 0.05 for all). The odds of recent HIV infection were higher among those who used one type (aOR = 2.2, 95% CI: 1.5-3.0) or two types of RD (aOR=2.3, 95% CI: 1.0-5.2) in the previous 6 months compared to the odds among those who did not use RDs. CONCLUSION: The level and pattern of multiple RD use among Chinese MSM were different from high-income countries. MSM who used more RDs are more likely to engage in high-risk sexual behaviors, and these behaviors may be associated with increases in new HIV infections.

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.

Characterization of the hemolytic activity of Riemerella anatipestifer.

Riemerella anatipestifer infection causes serious economic losses in the duck industry worldwide. Acute septicemia and high blood bacterial loading in R. anatipestifer infected ducks indicate that R. anatipestifer may be able to obtain iron and other nutrients by lysing duck erythrocytes to support its rapid growth and proliferation in the blood. However, so far, little is known about the hemolytic activity of R. anatipestifer to duck erythrocytes. In this study, 29 of 52 R. anatipestifer strains showed hemolytic activity on duck blood agar, whereas all the tested dba+ (with hemolytic activity on duck blood agar) and dba- strains created pores in the duck red blood cells, with 4.35-9.03% hemolytic activity in a liquid hemolysis assay after incubation for 24 h. The concentrated culture supernatants of all the tested R. anatipestifer strains and the extracted outer membrane proteins (OMPs) from dba+R. anatipestifer strains showed hemolytic activity on duck blood agar. These results, together with the median lethal dose (LD50) of some dba+ and dba-R. anatipestifer strains in ducklings, suggested that there was no direct relationship between the hemolytic capacity of R. anatipestifer on duck blood agar and its virulence.

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.

Evaluation of the protective immunity of Riemerella anatipestifer OmpA.

Riemerella anatipestifer is responsible for an economically important disease of commercially raised ducks. No or only few cross-protection was observed between different serotypes of R. anatipestifer strains, and so far no protective antigen in this bacterium has been identified. OmpA is a predominant immunogenic protein of R. anatipestifer, and within the 1467 bp ompA ORF (ompA1467), there is another 1164 bp ORF (ompA1164) with the same C-terminal. In this study, our results showed that the full sequence of ompA1467 from some R. anatipestifer strains with different serotypes shared the same amino acid sequence. Animal experiments showed that the soluble recombinant protein rOmpA1164, but not rOmpA1467, could provide partial protective immunity against challenge. Moreover, there was no significant difference in protective immunity between ducklings immunized with Th4△ompA bacterin and those immunized with Th4 bacterin. In addition, OmpA1467 was the main existing form of OmpA in R. anatipestifer cells by gel electrophoresis and western blot analyses. The results suggested that OmpA1467 was not a protective antigen of R. anatipestifer, and antibodies against proteins other than OmpA play a critical role in the process of anti-R. anatipestifer infection.

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.

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.

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.].

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.

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.

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.