Laboratory Core

该IP/CP授权的微生物学/病毒学核心B“替诺福韦和UC 781的替代制剂”是 完全融入本提案，为所有4个项目提供支持和互动。核心带来 抗逆转录病毒（ARV）药物、赋形剂和 制剂。微生物学/病毒学核心B将通过筛选辅料支持制剂项目1 和配制的膜，以确保它们对代表正常阴道炎的乳酸杆菌没有活性， 植物群，并筛选赋形剂对性传播病原体（STP）的活性。阴道正常 已知植物群在预防HIV-1和其他性病感染方面很重要。该核心将提供 使用宫颈外植块和上皮细胞单层培养物对配制的抗逆转录病毒药物安全性进行标准化检测 支持项目1、2、3和4。抗逆转录病毒药物薄膜的疗效和性交时间测试将使用 支持项目2、3和4，同时指导项目1中的制剂的宫颈外植块培养。核心B 将支持动物和人体试验，使用离体活检来证明对SHIV/HIV-1的保护作用。 感染（支持所有项目）。项目2和3中使用的薄膜和凝胶制剂的效果将是 通过核心区的培养工作进行监测，以监测微生物菌群。在项目3中，该核心将筛选受试者 STP和正常菌群，以确保受试者符合入选标准。宫颈阴道灌洗（CVL） 将在项目2、3和4中采集样本并用于药代动力学研究。本核心将利用这些 CVL，以通过检查和/或测定制剂是否干扰天然先天免疫过程， 安慰剂和含药物的薄膜和凝胶对杀死HIV-1、HSV和细菌的作用。还有， 阴道分泌物含有已知的杀死HSV和一些细菌的因子。一种有效的杀微生物剂 干扰这些过程，同时抑制HIV-1或防止其感染。总体而言，这 IP/CP寻求开发一种安全预防HIV-1感染而不干扰正常植物群的产品， 其他自然防御，这个核心将确保一个成功的杀微生物剂候选人被创造出来， 临床评价

The Microbiology/Virology Core B of this IP/CP Grant "Alternative Formulations of Tenofovir and UC781" is fully integrated into this proposal providing support and interactions with all 4 projects. This Core brings several new innovations to the safety and efficacy testing of antiretroviral (ARVs) drugs, excipients, and formulations. Microbiology/Virology Core B will support the Formulations Project 1 by screening excipients and formulated films to ensure they are not active against Lactobacillus representative of normal vaginal flora and to screen for excipient activity against sexually transmitted pathogens (STPs). The normal vaginal flora is known to be important in the prevention of infection by HIV-1 and other STPs. This Core will provide standardized testing of formulated ARV safety using ecto-cervical explant and epithelial monolayer cultures in support of Projects 1, 2, 3 and 4. ARV film efficacy and coital timing testing will be performed using the ecto-cervical explant cultures supporting Projects 2, 3, and 4 while guiding formulations in Project 1. Core B will support the animal and human trials using ex vivo biopsies to demonstrate protection from SHIV/HIV-1 infection (supporting all projects). The effects of films and gel preparation used in Projects 2 and 3 will be monitored by culture work in the Core to monitor the microflora. In Project 3, this Core will screen subjects for STPs and normal floras to assure subjects meet inclusion criterion. Cervicovaginal lavages (CVLs) samples will be collected in Projects 2, 3 and 4 and for pharmacokinetic study. This Core will utilize those CVL to determine if the and/or formulation interfere with the natural innate immunity process by examining the effects of placebo and drug containing films and gels on the killing of HIV-1, HSV, and bacteria. Also, vaginal fluid contains factors known to kill HSV as well as some bacteria. An effective microbicide can not interfere with these processes and at the same time inactivate HIV-1 or prevent its' infection. Overall, this IP/CP seeks to develop a product which prevents HIV-1 infection safely without disturbing the normal flora or other natural defenses and this Core will ensure a successful microbicide candidate is created for further clinical evaluation.