Preclinical evaluation of anti-HIV microbicide products: New models and biomarkers

Antiviral Res. 2010 Dec;88 Suppl 1:S10-8. doi: 10.1016/j.antiviral.2010.09.018.

Abstract

A safe and effective microbicide product designed to prevent sexual transmission of HIV-1 rests on a solid foundation provided by the proper selection and preclinical characterization of both its active pharmaceutical ingredient (API) and formulation. The evaluation of API and formulation physicochemical properties, drug release, specific antiviral activity, cell and tissue toxicity, organ toxicity, pharmacokinetics, and pharmacodynamics and efficacy provides information to understand the product, make go/no go decisions in the critical path of product development and complete a regulatory dossier to file an investigational new drug (IND) with the US Food and Drug Administration. Incorporation of new models, assays and biomarkers has expanded our ability to understand the mechanisms of action underlying microbicide toxicity and efficacy, enabling a more rational selection of drug and formulation candidates. This review presents an overview of the models and endpoints used to comprehensively evaluate an anti-HIV microbicide in preclinical development. This article forms part of a special supplement on presentations covering HIV transmission and microbicides, based on the symposium "Trends in Microbicide Formulations", held on 25 and 26 January 2010, Arlington, VA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Anti-HIV Agents / analysis
  • Anti-HIV Agents / therapeutic use
  • Anti-Infective Agents / administration & dosage*
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacokinetics*
  • Anti-Infective Agents / therapeutic use*
  • Anti-Infective Agents / toxicity
  • Biomarkers, Pharmacological
  • Dosage Forms
  • Drug Evaluation, Preclinical
  • Drug and Narcotic Control
  • Endpoint Determination
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / prevention & control*
  • HIV Infections / transmission
  • HIV-1* / drug effects
  • Humans
  • Investigational New Drug Application
  • Male
  • Models, Animal
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • Anti-Infective Agents
  • Biomarkers, Pharmacological
  • Dosage Forms