Effects of methamphetamine use on risk behavior, systemic and mucosal inflammation, and sexually transmitted infection (STI)/HIV risk among men who have sex with men

项目概要/摘要 这个K23职业发展奖将提供早期的职业生涯支持的行为和 男性中使用甲基苯丙胺（MA）导致艾滋病毒/性传播感染的生物风险因素， 男同性恋（MSM）该K23奖项将为候选人提供支持，以发展在 以下领域：1）MA使用和成瘾药物的生物学影响; 2）临床试验方法和 生物行为干预; 3）应用免疫学; 4）专业发展; 5）负责任的行为 的研究。布莱尔博士将接受一个多学科团队的指导，该团队在成瘾，传染病， 疾病免疫学和统计学史蒂文·肖普托博士在成瘾研究方面有着广泛的记录 以及培训未来的独立调查员。Jesse Clark博士将在临床试验中提供指导 方法，操作和安全程序; Grace Aldrovandi博士将提供应用指导 免疫学，重点是粘膜免疫学;罗伯特韦斯博士将提供指导， 先进的统计方法。MA的使用是艾滋病毒传播和新兴STI的重要驱动因素 流行于MSM。了解艾滋病毒/性传播感染的生物和行为风险因素的相互作用 使用MA导致的传播是有效的艾滋病毒/性传播感染干预措施的必要条件。布莱尔博士提议 研究MA使用、HIV、性风险行为和直肠淋病/衣原体（GC/CT）对 全身和直肠炎症。储存的血浆标本和每6个月获得的行为数据， 从140名MSM开始的2年将用于评估HIV和MA使用对全身炎症的联合影响 使用2x2析因设计，按HIV血清状态（70例阳性; 70例阴性）和结果分层， 尿MA筛查（70例使用MA; 70例未使用MA）。40例HIV阴性的使用性行为的MSM（20例直肠 GC/CT; 20例无直肠GC/CT）将从基于社区的大学研究中单独招募 诊所MA暴露将使用应急管理（CM）进行操纵，以评估 减少MA对炎症生物标志物的使用（例如，细胞因子）。开始CM后，性风险 行为将每周评估一次，持续8周。将每周测量炎症性直肠细胞因子， 直肠拭子，并与8周内MA暴露的生物标志物相关。这些活动将实现 以下目的：1）测量HIV和MA使用对全身细胞因子浓度和风险的联合影响 2）确定MA暴露和伴随直肠GC/CT对直肠细胞因子的影响 浓度;和3）评估MA使用频率与性风险行为的关联， 直肠炎症通过这个K23职业发展奖，布莱尔博士将确立自己作为一个 独立的临床研究员，具有生物学和行为学交叉研究的专业知识， MA和其他药物对HIV/STI传播动态的影响。

PROJECT SUMMARY/ABSTRACT This K23 Career Development Award will provide early career support for the investigation of behavioral and biological risk factors for HIV/STI transmission caused by methamphetamine (MA) use among men who have sex with men (MSM). This K23 award will provide support for the candidate to develop expertise in the following areas: 1) Biological impacts of MA use and addiction medicine; 2) Clinical trials methods and biobehavioral interventions; 3) Applied immunology; 4) Professional development; and 5) Responsible conduct of research. Dr. Blair will be mentored by a multidisciplinary team with expertise in addiction, infectious diseases, immunology, and statistics. Dr. Steven Shoptaw has an extensive track record in addiction research and training of future independent investigators. Dr. Jesse Clark will provide mentorship in clinical trial methods, operations, and safety procedures; Dr. Grace Aldrovandi will provide mentorship in applied immunology, with an emphasis on mucosal immunology; and Dr. Robert Weiss will provide mentoring in advanced statistical methods. MA use is an important driver of HIV transmission and the burgeoning STI epidemic among MSM. Understanding the interaction of biological and behavioral risk factors for HIV/STI transmission caused by MA use is imperative for effective HIV/STI interventions. Dr. Blair proposes to investigate the joint effects of MA use, HIV, sexual risk behavior, and rectal gonorrhea/chlamydia (GC/CT) on systemic and rectal inflammation. Stored plasma specimens and behavioral data obtained every 6 months over 2 years from 140 MSM will be used to assess the joint effects of HIV and MA use on systemic inflammation and risk behavior using a 2x2 factorial design stratified by HIV serostatus (70 positive; 70 negative) and results of urine MA screening (70 with MA use; 70 without MA use). 40 HIV-negative MA-using MSM (20 with rectal GC/CT; 20 without rectal GC/CT) will be recruited separately from a community-based university research clinic. MA exposure will be manipulated using contingency management (CM) to evaluate the effects of a decline in MA use on biological markers of inflammation (e.g., cytokines). Following initiation of CM, sexual risk behaviors will be assessed weekly for 8 weeks. Inflammatory rectal cytokines will be measured weekly with rectal swabs and linked with biomarkers of MA exposure over 8 weeks. These activities will accomplish the following aims: 1) Measure the joint effects of HIV and MA use on systemic cytokine concentrations and risk behavior; 2) Identify the effects of MA exposure and concomitant rectal GC/CT on rectal cytokine concentrations; and 3) Evaluate the association of MA use frequency with sexual risk behavior in the setting of rectal inflammation. Through this K23 Career Development Award, Dr. Blair will establish herself as an independent clinician-investigator with expertise in intersectional research on the biological and behavioral impacts of MA and other drugs on HIV/STI transmission dynamics.