Microbicides for the Prevention of HIV Transmission

In Vitro Efficacy Evaluations

This service provides evaluation of products which already have been evaluated in a biochemical or cell-based assay and 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.

Products are evaluated for topical microbicide potential using the following screening algorithm (published in Antimicrobial Agents and Chemotherapy. 2008 May; 52(5): 1768–1781).

Primary Assays

1. CD4-dependent CCR5-tropic cell-associated HIV-1 transmission inhibition and cytotoxicity assays
2. 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 for colorless products or ≥50 for colored products, Confirmatory Assays will be initiated. If TIs fail to meet these cutoffs, further evaluation of the product is terminated.

Confirmatory Assays

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

Decision Point: If TIs remain ≥10 for colorless products or ≥50 for colored products, Secondary Assays will be initiated. If TIs fail to meet these cutoffs, further evaluation of the product is terminated.

Secondary Assays

1. CD4-dependent CCR5-tropic HIV-1 fusion inhibition assay
2. CD4-dependent CXCR4-tropic cell-associated HIV-1 transmission inhibition assay
3. CD4-dependent CXCR4-tropic HIV-1 entry inhibition assay
4. CD4-dependent CXCR4-tropic HIV-1 fusion inhibition assay
5. CD4-independent HIV-1 transmission inhibition assay (ME-180 assay)
6. Primary assays modified to incorporate 25% seminal plasma
7. Primary assays modified to incorporate a pH transition step
8. Lactobacillus growth inhibition assay

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

Specialized Assays

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

The current contractor for this service is Southern Research Institute, Frederick, Maryland.​​