A Molecular-Social Network Investigation of HIV-HCV Co-infection in Chinese MSM

描述（由申请人提供）：HCV是中国发病率和死亡率不断上升的原因，估计人均患病率是美国的三倍。虽然数据有限，但HCV的发病率也被认为在增加。然而，不安全性行为对高危人群（如MSM（男男性行为者））中HCV持续传播的贡献尚不清楚。与此同时，中国估计有300万至1800万男男性接触者，艾滋病发病率和流行率非常高。由于无保护肛交的高发生率和HIV感染的高发生率，中国MSM中HIV阳性的人数预计将增加。在中国，大多数关于HCV的研究检查了非肠道传播原因，如静脉吸毒（IDU）、血浆献血或医疗相关感染，而没有关注HCV的性传播。最近在西方国家的研究表明，HCV感染流行的男男性接触者，是无关的胃肠外传播。研究表明，HCV的性传播，特别是在HIV感染的MSM中，由于直肠合并感染和/或粗暴的性行为导致粘膜破裂。还有来自中国MSM的受访者驱动抽样数据表明亲密伴侣暴力的发生率很高，这也可能有助于同性恋HCV传播。通过探讨已确定的HIV感染MSM的伴侣的HCV状态，我们的目的是研究性活动在HCV传播中的作用。因此，使用已知临床人群的混合方法设计（即，HIV阳性的中国男男性接触者），我们建议（1）建立性风险的差异和联合贡献（例如，无保护，接受肛交） 和IDU到HCV在HIV感染的中国MSM及其IDU和性伴侣中的传播;（2）建立HCV和HIV的分子流行病学（通过基因分型和系统发育分析）;描述和检查生物社会相关性（例如，病毒载量;多个性伴侣;性风险;多个吸毒伙伴，跨代吸毒）与缺乏通过这两种途径传播;（4）描述和检查与HCV的性和/或药物风险决定因素相关的行为和社会网络特征（自我中心）;（5）基于这些发现建立预期HCV-HIV发病率模型。我们的研究具有很高的公共卫生意义，因为随着最近慢性HCV治疗新疗法（如直接作用剂）的出现，HCV已成为一种高度可治疗的疾病，但许多感染者仍然不知道自己的病情。这项研究的创新之处在于，它更深入地研究了性传播的具体途径，而以前的许多研究对所有性伴侣都不加区别地进行了分类。行为网络分析和HCV和HIV系统发育分析的整合为制定针对HCV和HIV共感染MSM的预防策略提供了更有力的证据。

DESCRIPTION (provided by applicant): HCV is an increasing cause of morbidity and mortality in China, with an estimated per capita prevalence that is three-fold that of the United States. Although there are limited data, HCV incidence is also thought to be increasing. However, the contribution of unsafe sex to ongoing HCV transmission among high-risk groups such as MSM (men who have sex with men) is not well understood. Meanwhile, China's estimated three to 18 million MSM exhibit very high HIV incidence and prevalence rates. The number of HIV-positive Chinese MSM is expected to increase due to high rates of unprotected anal intercourse and the high incidence of HIV infection. Most studies on HCV in China examine parenteral causes of transmission such as intravenous drug use (IDU), plasma blood donation, or medical treatment-related infections, and have not focused on sexual transmission of HCV. Recent studies in Western countries have shown an epidemic of HCV infection among MSM that is unrelated to parenteral spread. Studies suggest sexual transmission of HCV, especially among HIV-infected MSM, due to rectal co-infections and/or rough sex leading to mucosal breakdown. There are also respondent driven sampling data from MSM in China suggesting a high rate of intimate partner violence, which may also contribute to homosexual HCV transmission. By exploring the HCV status of partners of established HIV-infected MSM, we aim to study the contribution that sexual activity plays in HCV transmission. Therefore, using a mixed-method design with a known clinical population (i.e., HIV-positive Chinese MSM), we propose to (1) establish the differential and joint contribution of sexual risks (e.g., unprotected, receptive anal intercourse) and IDU to HCV transmission among HIV-infected Chinese MSM and their IDU and sexual partners; (2) establish the molecular epidemiology of HCV and HIV (via genotyping and phylogenetic analysis); describe and examine biosocial correlates (e.g., viral load; multiple sexual partners; sexual risks; multiple drug-using partners, cross-generational drug use) associated with lack of transmission via these two routes; (4) describe and examine behavioral and social network characteristics (egocentric) associated with sexual and/or drug risk determinants of HCV; and (5) model expected HCV-HIV morbidity based on these findings. Our study has high public health significance because, with the recent advent of new therapies for chronic HCV treatment (such as direct-acting agents), HCV has become a highly treatable disease yet many infected persons remain unaware of their condition. The study is innovative in that it delves more deeply into specific routes of sexual transmission, whereas many previous studies classified all sexual partners without distinction. The integration of behavioral network analysis and HCV and HIV phylogenetic analysis provides enhanced evidence for developing tailored prevention strategies for HCV-HIV co-infected MSM.