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

项目摘要/摘要 K23职业发展奖将为调查行为和职业发展提供早期职业支持 男性中使用甲基苯丙胺(MA)导致HIV/STI传播的生物学危险因素 男男性性行为(MSM)。这项K23奖项将为候选人提供支持，使其在 以下领域：1)MA使用和成瘾药物的生物影响；2)临床试验方法和 生物行为干预；3)应用免疫学；4)职业发展；5)负责任的行为 研究的成果。布莱尔博士将接受一个多学科团队的指导，该团队拥有成瘾、传染性方面的专业知识 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 以及对未来独立调查人员的培训。杰西·克拉克博士将在临床试验中提供指导 方法、手术和安全程序；Grace Aldrovandi博士将在应用 免疫学，重点是粘膜免疫学；Robert Weiss博士将在 先进的统计方法。吸食吸毒者是艾滋病毒传播和迅速发展的性传播的重要驱动力 在男男性接触者中流行。了解HIV/STI的生物学和行为危险因素的相互作用 使用MA引起的传播对于有效的艾滋病毒/性传播感染干预是必不可少的。布莱尔博士建议 研究MA使用、HIV、性危险行为和直肠淋病/衣原体(GC/CT)对 全身和直肠炎症。每6个月存储一次的血浆样本和行为数据 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 风险行为采用2x2析因设计，按HIV血清状态(70阳性；70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MA-使用男男性接触者(20例直肠 GC/CT；没有直肠GC/CT的20人)将从以社区为基础的大学研究中单独招募 诊所。将使用应急管理(CM)来控制MA暴露，以评估 MA在炎症生物标志物(如细胞因子)上的使用减少。在CM开始后，性风险 每周进行一次行为评估，为期8周。每周将测量直肠炎性细胞因子 取直肠拭子，并与MA暴露8周以上的生物标志物相关联。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 行为；2)确定MA暴露及其伴发的直肠GC/CT对直肠细胞因子的影响 浓度；以及3)评估在以下情况下使用MA的频率与性危险行为的关联 直肠炎。通过K23职业发展奖，布莱尔博士将确立自己作为 独立的临床医生-调查员，在生物学和行为学的交叉研究方面具有专业知识 MA和其他药物对HIV/STI传播动力学的影响。

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.