Anton Peter A
David Geffen School of Medicine and Center for HIV Prevention Research, University of California Los Angeles, Los Angeles, CA, USA.
Curr HIV Res. 2012 Jan 1;10(1):113-5. doi: 10.2174/157016212799304634.
As 'proof of concept' has now been well validated for topical microbicides, the progress has, appropriately, refined the questions of who, how, when and at what risk and cost. These are welcome challenges requiring intensified, cross-disciplinary responses. This is especially true in the areas of adherence and pharmacokinetic/pharmacodynamics (PK/PD) sampling and modeling to optimize preventive trials measuring "efficacy", which is well known to reduce when measured as "effectiveness" in real-world use. Intensified exploratory and Phase 1 safety trials to investigate acceptability, adherence, PK and ex vivo efficacy with drug-exposed tissue biopsies/compartment fluids even though they are complex in design, management, assays and monitoring are moving forward As well, great strides in recent efforts in a variety of delivery formulations are promising. These current and future efforts will provide potential insights earlier that at Phase IIb or III in the development pipeline.
由于局部用杀微生物剂的“概念验证”现已得到充分验证，研究进展已恰当地细化了关于何人、如何、何时以及面临何种风险和成本的问题。这些都是值得欢迎的挑战，需要加强跨学科应对。在依从性以及药代动力学/药效学（PK/PD）采样与建模等领域尤其如此，以优化衡量“疗效”的预防性试验，众所周知，在实际使用中将其作为“效果”衡量时，疗效会降低。尽管设计、管理、检测和监测都很复杂，但针对药物暴露的组织活检/隔室液进行的强化探索性试验和1期安全性试验，以研究可接受性、依从性、药代动力学和体外疗效，正在推进。此外，近期在各种给药制剂方面的努力取得了巨大进展，前景乐观。这些当前和未来的努力将比研发流程中的IIb期或III期更早地提供潜在见解。
