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

描述(申请人提供)：丙型肝炎病毒是中国发病和死亡的一个日益增加的原因，估计人均流行率是美国的三倍。尽管数据有限，但丙型肝炎病毒的发病率也被认为在增加。然而，不安全的性行为在MSM(男男性行为者)等高危人群中持续传播丙型肝炎病毒的作用尚未得到很好的了解。与此同时，中国估计有300万至1800万男男性接触者表现出非常高的艾滋病毒发病率和流行率。由于无保护肛交的高比率和艾滋病毒感染的高发生率，中国HIV阳性男男性接触者的数量预计将增加。中国对丙型肝炎病毒的研究多集中在静脉吸毒、血浆献血、医疗相关感染等肠外传播途径上，对丙型肝炎病毒的性传播研究较少。最近在西方国家的研究表明，在MSM中流行的丙型肝炎病毒感染与肠道外传播无关。研究表明，由于直肠混合感染和/或粗暴的性行为导致粘膜破裂，丙型肝炎病毒的性传播，特别是在感染艾滋病毒的男男性接触者中。来自中国男男性接触者的调查样本数据显示，亲密伴侣的暴力行为发生率很高，这也可能是同性恋传播丙型肝炎病毒的原因之一。通过探讨感染HIV的男男性接触者伴侣的丙型肝炎病毒状态，我们的目的是研究性行为在丙型肝炎传播中的作用。因此，采用混合方法设计，以已知的临床人群(即HIV阳性的中国男男性接触者)为对象，我们建议(1)建立性行为风险(例如，无保护的、接受性的肛交)的不同和联合贡献。 (2)建立丙型肝炎病毒和艾滋病毒的分子流行病学(通过基因分型和系统发育分析)；描述和研究与未通过这两条途径传播有关的生物社会关联(例如，病毒载量；多个性伴侣；性风险；多个吸毒者，跨代吸毒)；(4)描述和研究与丙型肝炎病毒的性和/或药物风险决定因素相关的行为和社会网络特征(以自我为中心)；以及(5)基于这些发现建立预期的丙型肝炎病毒-艾滋病毒发病率模型。我们的研究具有很高的公共卫生意义，因为随着最近出现的治疗慢性丙型肝炎的新方法(如直接作用药物)，丙型肝炎已经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，它更深入地探索性传播的具体途径，而之前的许多研究对所有性伴侣进行了不区分的分类。行为网络分析与丙型肝炎病毒和艾滋病病毒系统发育分析的结合为制定针对丙型肝炎病毒和艾滋病病毒共同感染的男男性行为者的预防策略提供了更好的证据。

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.