ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer

Purpose: ErbB2 signaling appears to be increased and may enhance AR activity in a subset of CRPC, but agents targeting ErbB2 have not been effective. This study was undertaken to assess ErbB2 activity in abiraterone-resistant prostate cancer (PCa), and determine whether it may contribute to androgen receptor (AR) signaling in these tumors. Experimental Design: AR activity and ErbB2 signaling were examined in the radical prostatectomy specimens from a neoadjuvant clinical trial of leuprolide plus abiraterone, and in the specimens from abiraterone-resistant CRPC xenograft models. The effect of ErbB2 signaling on AR activity was determined in two CRPC cell lines. Moreover, the effect of combination treatment with abiraterone and an ErbB2 inhibitor was assessed in a CRPC xenograft model. Results: We found that ErbB2 signaling was elevated in residual tumor following abiraterone treatment in a subset of patients, and was associated with higher nuclear AR expression. In xenograft models, we similarly demonstrated that ErbB2 signaling was increased and associated with AR reactivation in abiraterone-resistant tumors, while ERBB2 message level was not changed. Mechanistically, we show that ErbB2 signaling and subsequent activation of the PI3K/AKT signaling stabilizes AR protein. Inhibitors targeting ErbB2/PI3K/AKT pathway disrupt AR transcriptional activity. Furthermore, concomitantly treating CRPC xenograft with abiraterone and an ErbB2 inhibitor, lapatinib, blocked AR reactivation and suppressed tumor progression. Conclusions: ErbB2 signaling is elevated in a subset of abiraterone-resistant prostate cancer patients and stabilizes AR protein. Combination therapy with abiraterone and ErbB2 antagonists may be effective for treating the subset of CRPC with elevated ErbB2 activity

Pressured HIV testing "in the name of love": a mixed methods analysis of pressured HIV testing among men who have sex with men in China.

INTRODUCTION: HIV testing has rapidly expanded into diverse, decentralized settings. While increasing accessibility to HIV testing is beneficial, it may lead to unintended consequences such as being pressured to test. We examined the frequency, correlates and contexts of pressured HIV testing among Chinese men who have sex with men (MSM) using mixed methods. METHODS: We conducted an online survey of MSM (N = 1044) in May 2017. Pressured HIV testing was defined as being forced to test for HIV. We conducted logistic regression analysis to determine the associations between pressured HIV testing and socio-demographic and sexual behavioural factors. Follow-up interviews (n = 17) were conducted with men who reported pressured testing and we analysed qualitative data using a thematic analysis approach. RESULTS: Ninety-six men (9.2%) reported experiencing pressure to test for HIV. Regular male sex partners were the most common source of pressure (61%, 59/96), and the most common form of pressure was a threat to end a relationship with the one who was being pressured (39%, 37/96). We found a higher risk of pressured testing in men who had only used HIV self-testing compared to men who had never self-tested (AOR 2.39 (95%CI: 1.38 to 4.14)). However, this relationship was only significant among men with low education (AOR 5.88 (95% CI: 1.92 to 17.99)) and not among men with high education (AOR 1.62 (95% CI: 0.85 to 3.10)). After pressured testing, about half of men subsequently tested for HIV (55%, 53/96) without pressure - none reported being diagnosed with HIV. Consistent with this finding, qualitative data suggest that perceptions of pressure existed on a continuum and depended on the relationship status of the one who pressured them. Although being pressured to test was accompanied by negative feelings, men who were pressured into testing often changed their attitude towards HIV testing, testing behaviours, sexual behaviours and relationship with the one who pressured them to test. CONCLUSION: Pressured HIV testing was reported among Chinese MSM, especially from men with low education levels and men who received HIV self-testing. However, in some circumstances, pressure to test helped MSM in several ways, challenging our understanding of the role of agency in the setting of HIV testing

What happens after HIV self-testing? Results from a longitudinal cohort of Chinese men who have sex with men.

BACKGROUND: HIV self-testing (HIVST) is a promising approach to expand HIV testing. HIVST is a process in which a person performs an HIV test and interprets the result. Negative HIVST results may encourage men who have sex with men (MSM) to use HIV prevention services. The objective of this study was to examine behaviors (e.g., facility-based HIV testing, condom use) after a negative HIVST test result among Chinese MSM. METHODS: We collected data from MSM in eight Chinese cities over a 12-month period. This is a secondary analysis of longitudinal cohort data collected as part of an intervention trial to increase HIV testing. Men completed a survey that described sociodemographic information, sexual behaviors, HIV self-testing, and facility-based HIV testing. Men who completed at least one follow-up survey were included in this analysis. Generalized linear mixed models were used to evaluate whether HIVST increased subsequent facility-based HIV testing and consistent condom use. RESULTS: We included 1219 men. Most men (78.7%) were under 30 years old and had never been married (87.0%). 755 (61.9%) men tested for HIV and 593 (49.3%) men self-tested during the study period. At baseline, among men who had never been tested for HIV, 44.9% (314/699) initiated HIVST during the study period. HIVST was associated with subsequent facility-based testing (aOR of 1.87, 95% CI: 1.47-2.37). HIVST was also associated with subsequent consistent condom use (aOR = 1.53, 95% CI: 1.13-2.06). CONCLUSION: HIVST was associated with subsequent facility-based HIV testing and consistent condom use. HIVST may enhance uptake of related HIV prevention services at facilities, suggesting the need for more implementation research

Leading by Example: Web-Based Sexual Health Influencers Among Men Who Have Sex With Men Have Higher HIV and Syphilis Testing Rates in China

BACKGROUND: The spread of healthy behaviors through social networks may be accelerated by influential individuals. Previous studies have used lay health influencers to prevent sexually transmitted infections (STIs) among internet-using men who have sex with men (MSM). However, there is a lack of understanding of the characteristics of this key subset of MSM. OBJECTIVE: This study aimed to examine sociodemographic characteristics, HIV and syphilis testing, and sexual behaviors of Web-based MSM sexual health influencers (SHIs) in China, defined as individuals with relatively stronger influence on spreading HIV and STI information online. METHODS: A Web-based survey of MSM was conducted in August 2017 as a final follow-up of a randomized controlled trial promoting HIV testing in 8 Chinese cities. Men were recruited through a gay social networking mobile phone app and were included if they were born biologically male, aged 16 years and above, ever had sex with another man, and HIV negative or with unknown HIV status. Information regarding sociodemographic characteristics, sexual behaviors, and HIV and syphilis testing was obtained. We assessed men's Web-based sexual health influence using a standardized 6-item opinion leadership scale focused on HIV and STI information. Influencers were defined as those whose mean score ranked within the top 13% (a higher score means greater influence). We used multivariable linear and logistic regression models to measure Web-based sexual health influence's association with HIV and syphilis testing, controlling for intervention trial effects, age, education, income, and marital status. RESULTS: Overall, 1031 men completed the survey. Most men were younger than 30 years (819/1031, 79.43%) and had at least college education (667/1031, 64.69%). Influencers were more likely to get tested for HIV (73/132, 55.3% vs 337/899, 37.5%; P<.001) and syphilis (35/132, 26.5% vs 137/899, 15.2%; P=.001) in the last 3 months compared with noninfluencers. There were no significant differences in condomless sex with male partners (26/132, 19.7% vs 203/899, 22.6%; P=.46), mean number of male sex partners (1.32 vs 1.11; P=.16) in the last 3 months, and mainly meeting male sex partners online in the last 12 months (97/132, 73.5% vs 669/899, 74.4%; P=.82) between influencers and noninfluencers. Regression analyses showed that influencers had higher odds of HIV testing (adjusted odds ratio, AOR 2.16, 95% CI 1.48-3.17) and syphilis testing (AOR 1.99, 95% CI 1.28-3.10) in the last 3 months. CONCLUSIONS: We identified Web-based SHIs who might be more likely to help promote healthy HIV and syphilis testing behaviors through MSM populations. Leveraging existing influencers may help improve HIV and syphilis testing among their networks

Crowdsourcing to expand HIV testing among men who have sex with men in China: A closed cohort stepped wedge cluster randomized controlled trial.

BACKGROUND: HIV testing rates are suboptimal among at-risk men. Crowdsourcing may be a useful tool for designing innovative, community-based HIV testing strategies to increase HIV testing. The purpose of this study was to use a stepped wedge cluster randomized controlled trial (RCT) to evaluate the effect of a crowdsourced HIV intervention on HIV testing uptake among men who have sex with men (MSM) in eight Chinese cities. METHODS AND FINDINGS: An HIV testing intervention was developed through a national image contest, a regional strategy designathon, and local message contests. The final intervention included a multimedia HIV testing campaign, an online HIV testing service, and local testing promotion campaigns tailored for MSM. This intervention was evaluated using a closed cohort stepped wedge cluster RCT in eight Chinese cities (Guangzhou, Shenzhen, Zhuhai, and Jiangmen in Guangdong province; Jinan, Qingdao, Yantai, and Jining in Shandong province) from August 2016 to August 2017. MSM were recruited through Blued, a social networking mobile application for MSM, from July 29 to August 21 of 2016. The primary outcome was self-reported HIV testing in the past 3 months. Secondary outcomes included HIV self-testing, facility-based HIV testing, condom use, and syphilis testing. Generalized linear mixed models (GLMMs) were used to analyze primary and secondary outcomes. We enrolled a total of 1,381 MSM. Most were ≤30 years old (82%), unmarried (86%), and had a college degree or higher (65%). The proportion of individuals receiving an HIV test during the intervention periods within a city was 8.9% (95% confidence interval [CI] 2.2-15.5) greater than during the control periods. In addition, the intention-to-treat analysis showed a higher probability of receiving an HIV test during the intervention periods as compared to the control periods (estimated risk ratio [RR] = 1.43, 95% CI 1.19-1.73). The intervention also increased HIV self-testing (RR = 1.89, 95% CI 1.50-2.38). There was no effect on facility-based HIV testing (RR = 1.00, 95% CI 0.79-1.26), condom use (RR = 1.00, 95% CI 0.86-1.17), or syphilis testing (RR = 0.92, 95% CI 0.70-1.21). A total of 48.6% (593/1,219) of participants reported that they received HIV self-testing. Among men who received two HIV tests, 32 individuals seroconverted during the 1-year study period. Study limitations include the use of self-reported HIV testing data among a subset of men and non-completion of the final survey by 23% of participants. Our study population was a young online group in urban China and the relevance of our findings to other populations will require further investigation. CONCLUSIONS: In this setting, crowdsourcing was effective for developing and strengthening community-based HIV testing services for MSM. Crowdsourced interventions may be an important tool for the scale-up of HIV testing services among MSM in low- and middle-income countries (LMIC). TRIAL REGISTRATION: ClinicalTrials.gov NCT02796963

Systemic Risks of Climate Events and Households’ Participation in Mariculture Mutual Insurance: A Case Study of Shrimp Producers in Zhejiang Province

Mariculture is playing an important role in food safety, acting as strong complement to marine fishery. As a typical capital intensive and high-risk sector, mariculture mutual insurance is important for ensuring the stability and sustainability of mariculture due to the inertia of private insurance, it is necessary to examine factors for low household participation in marine fishery mutual insurance to promote the healthy development of marine insurance. Based on the field surveyed data of mariculture shrimp producers in Zhejiang Province, this study aims to examine the determinants underlying households&#8217; participation in mariculture mutual insurance. Based on logistic model, we find out that climate risks, environmental risks and technical risks have seriously hindered the development of food security and fisheries in Zhejiang Province. In addition, farmers&#8217; insurance involvement mainly depends on the individual characteristics of the farmers: whether used to go out to work, perception of burden level of premium and insurance awareness; family characteristics of fish farmers: total household income, and unpaid loan; and production characteristics: professional level, mariculture area and whether sea waters registration. Meanwhile, external factors, including organizations available for insurance participation, impact of national insurance subsidies, policy support and disasters on the aquaculture area. Corresponding risk management measures are urgently needed for the sustainable development of mariculture