Microbicide Development Program (MDP)

杀菌剂开发计划 (MDP)

• 批准号: 7928470
• 负责人: Peter A Anton
• 金额: $ 12.2万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7928470
• 关键词: Microbicide; Development; Program; MDP

DESCRIPTION (provided by applicant): This proposal addresses the need to develop a rational, cost effective, and scientifically robust approach to the development of topical rectal microbicides from preclinical to exploratory studies in humans. The individual projects explore distinct, but overlapping areas of microbicide research that, cumulatively, will define the future of rectal microbicide development. The key premise that underpins the proposal is that receptive anal intercourse (RAI) is a common activity, playing a significant role in the transmission of HIV infection. Heterosexual RAI is common, with rates of 5-10% in US women and is considered to be the most common route of HIV transmission in men who have sex with men. Failure to acknowledge the role that RAI plays in the global AIDS pandemic is likely to limit the success of intervention strategies and compromise attempts to develop safe and effective vaginal microbicides. This MDP Project application is a U19, a collaborative effort with NIH and private sectors, to initiate coordinated, multidisciplinary research involving many of the world's experts in disciplines related to rectal microbicide development. We have focused our efforts on one class of microbicides, the reverse-transcriptase (RT) inhibitors (PMPA, UC-781, and TMC-120), two of which are in clinical trials as vaginal microbicide form. We have the support of three corporate sponsors (Biosyn, Inc., Gilead Sciences, and Tibotec-Virco) to initiate these efforts. The "preclinical" phase includes cell line, intestinal explant and macaque studies of microbicide safety and efficacy (Project by McGowan) which will progress microbicides into exploratory human trials designed to optimize microbicide safety evaluation, provide initial ex vivo/in vitro efficacy data, and information about distribution and bioavailability of RT microbicides (Project by Corner). The goal, over 5 years, will be to assess, what are the most cost effective and predictive assays for use in future microbicide development. Projects by Gorbach will target the role of RAI on mucosal function, the behavioral correlates of RAI, and acceptability studies of candidate formulations. Failure to adjust for these modifiers of safety and efficacy may result in (1) falsely attributing RAI toxicity to the microbicide and (2) failing to demonstrate efficacy because of simultaneous enhancement of HIV transmission due to RAI. The information derived from these studies will be critical for RT development, but will also provide a rational basis for the development of other classes of rectal microbicides.

描述（由申请人提供）：该提案解决了开发一种合理的、具有成本效益的、科学稳健的方法来开发从临床前到人类探索性研究的外用直肠杀菌剂的需要。各个项目探索了不同但重叠的杀微生物剂研究领域，这些领域累积起来将定义直肠杀微生物剂开发的未来。支持该提案的关键前提是接受性肛交（RAI）是一种常见的活动，在艾滋病毒感染的传播中发挥着重要作用。异性恋 RAI 很常见，在美国女性中的发病率为 5-10%，并且被认为是男男性行为者中最常见的 HIV 传播途径。如果不承认 RAI 在全球艾滋病流行中所发挥的作用，可能会限制干预策略的成功，并损害开发安全有效的阴道杀菌剂的尝试。 This MDP Project application is a U19, a collaborative effort with NIH and private sectors, to initiate coordinated, multidisciplinary research involving many of the world's experts in disciplines related to rectal microbicide development.我们的重点是一类杀菌剂，即逆转录酶 (RT) 抑制剂（PMPA、UC-781 和 TMC-120），其中两种作为阴道杀菌剂正在进行临床试验。我们得到了三个企业赞助商（Biosyn, Inc.、Gilead Sciences 和 Tibotec-Virco）的支持来启动这些努力。 “临床前”阶段包括针对杀微生物剂安全性和功效的细胞系、肠道外植体和猕猴研究（McGowan 项目），该阶段将把杀微生物剂推进探索性人体试验，旨在优化杀微生物剂安全性评估，提供初步的离体/体外功效数据以及有关 RT 杀微生物剂分布和生物利用度的信息（Corner 项目）。五年内的目标将是评估未来杀菌剂开发中最具成本效益和预测性的检测方法。 Gorbach 的项目将针对 RAI 对粘膜功能的作用、RAI 的行为相关性以及候选制剂的可接受性研究。 如果未能调整这些安全性和有效性的修正因素，可能会导致 (1) 错误地将 RAI 毒性归因于杀微生物剂，以及 (2) 由于 RAI 同时增强了 HIV 传播而未能证明有效性。从这些研究中获得的信息对于 RT 的开发至关重要，但也将为其他类别直肠杀菌剂的开发提供合理的基础。

项目成果

Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs.

• DOI: 10.3390/vaccines9030231
• 发表时间: 2021-03-08
• 期刊: Vaccines
• 影响因子: 7.8
• 作者: Herrera C;McRaven MD;Laing KG;Dennis J;Hope TJ;Shattock RJ
• 通讯作者: Shattock RJ

The slippery slope: lubricant use and rectal sexually transmitted infections: a newly identified risk.

• DOI: 10.1097/olq.0b013e318235502b
• 发表时间: 2012-01
• 期刊: Sexually transmitted diseases
• 影响因子: 3.1
• 作者: Gorbach PM;Weiss RE;Fuchs E;Jeffries RA;Hezerah M;Brown S;Voskanian A;Robbie E;Anton P;Cranston RD
• 通讯作者: Cranston RD

Advances in the Development of Microbicides for the Prevention of HIV Infection.

• DOI: 10.1007/s11908-009-0076-5
• 发表时间: 2010-01-01
• 期刊: Current infectious disease reports
• 影响因子: 3.1
• 作者: Minces, Lucio R;McGowan, Ian
• 通讯作者: McGowan, Ian

Use of the location-based social networking application GRINDR as a recruitment tool in rectal microbicide development research.

将基于位置的社交网络应用程序Grindr用作直肠菌心发展研究中的招聘工具。

• DOI: 10.1007/s10461-012-0277-z
• 发表时间: 2012-10
• 期刊: AIDS AND BEHAVIOR
• 影响因子: 4.4
• 作者: Burrell, Earl R.;Pines, Heather A.;Robbie, Edward;Coleman, Leonardo;Murphy, Ryan D.;Hess, Kristen L.;Anton, Peter;Gorbach, Pamina M.
• 通讯作者: Gorbach, Pamina M.

Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel.

• DOI: 10.1371/journal.pmed.0050157
• 发表时间: 2008-08-05
• 期刊: PLoS medicine
• 影响因子: 15.8
• 作者: Cranage M;Sharpe S;Herrera C;Cope A;Dennis M;Berry N;Ham C;Heeney J;Rezk N;Kashuba A;Anton P;McGowan I;Shattock R
• 通讯作者: Shattock R