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Microbicides to Prevent HIV Transmission In Vitro

This service provides evaluation of products that have already been evaluated in a biochemical or cell-based assay and shown to possess an activity profile that warrants further development as a microbicide. NIAID does NOT offer the primary screening of previously untested products via this service. Products must be single-component entities of known chemical structure; evaluation of multi-component natural product extracts is not supported.

Products are evaluated for their potential as a topical microbicide using a series of defined assays that generate measurements of relative antiviral potency. The screening algorithm was published in Antimicrobial Agents and Chemotherapy. 2008 May; 52(5): 1768–1781

Main Areas of Focus

  • To fill specific gaps in an investigator’s drug development plan as they advance their product toward clinical investigation.
  • These services are provided at no cost to the investigator.

Investigators seeking these services receive no funding from NIAID, but instead receive products or information generated by NIAID-funded contractors on their behalf.

Support Services

  • Evaluation of products to help further development of the product as a microbicide.

Tools

Primary Assays

  • CD4-dependent CCR5-tropic cell-associated HIV-1 transmission inhibition and cytotoxicity assays
  • CD4-dependent CCR5-tropic cell-free HIV-1 entry inhibition and cytotoxicity assays

Decision Point: If Therapeutic Index (TI= TC50/IC50, where TC50 = 50% inhibitory concentration in cytotoxicity assay and IC50 = 50% inhibitory concentration in anti-HIV assay) for Primary Assay 1 is ≥10  Confirmatory Assays will be initiated. If TIs fail to meet this cutoff, further evaluation of the product is terminated.

Confirmatory Assays

  • Repeat of CD4-dependent CCR5-tropic cell-associated HIV-1 transmission inhibition and cytotoxicity assays
  • Repeat of CD4-dependent CCR5-tropic cell-free HIV-1 entry inhibition and cytotoxicity assays

Decision Point: If TIs remain ≥10  Secondary Assays will be initiated. If TIs fail to meet this cutoff, further evaluation of the product is terminated.

Secondary Assays

  • CD4-dependent CCR5-tropic HIV-1 fusion inhibition assay
  • CD4-dependent CXCR4-tropic cell-associated HIV-1 transmission inhibition assay
  • CD4-dependent CXCR4-tropic HIV-1 entry inhibition assay
  • CD4-dependent CXCR4-tropic HIV-1 fusion inhibition assay
  • CD4-independent HIV-1 transmission inhibition assay (ME-180 assay)
  • Primary assays modified to incorporate 25% seminal plasma
  • Primary assays modified to incorporate a pH transition step
  • Lactobacillus growth inhibition assay

Decision Point: The most highly ranked compounds from Secondary Assays are evaluated in Specialized Assays.

Specialized Assays

  • Human cervical explant model
  • Human PBMC clade panel testing
  • Combination drug assays
  • Specialized cytotoxicity (Vybrant and LIVE/DEAD) assays.

Who Can Use This Resource

  • Products must already have been evaluated in a biochemical or cell-based assay.
  • Products must have shown to possess an activity profile that warrants further development of the product as a microbicide.
  • NIAID does NOT offer the primary screening of previously untested products via this service.
  • Products must be single-component entities of known chemical structure; evaluation of multi-component natural product extracts is not supported.

How To Get Started

  • Follow the procedures for requesting access to NIAID contract services.
  • In addition, data packages for In Vitro efficacy evaluations requests should also address the following: 
    • Proposed mode of action of product
    • Assessment of product’s efficacy against the requested pathogen or a closely related pathogen, or activity in a biochemical or cell-based screen that supports the proposed mode of action
    • Assessment of product’s cytotoxicity against uninfected cells
Content last reviewed on November 17, 2017