Testing Candidate Topical Microbicides – Distinguishing Toxicity from Efficacy in Preclinical Testing
Year: 2005
Type: article
Abstract: Topical microbicides are considered an affordable choice for the prevention of sexually transmitted diseases in women. We have developed a comprehensive testing program for preclinical microbicide development. Over the years, we have tested several thousand compounds for use as topical microbicides in a series of cell-based assays addressing HIV-1 efficacy and toxicity. Recently, we compared historical data of the spermicide nonoxynol-9 (N-9) in a multi-center study and found that the HIV-1 efficacy paralleled its toxicity. Intra-assay, inter-assay, and interlaboratory variability for toxicity were remarkably consistent. In a recent clinical trial, N-9 was found to enhance HIV-1 infection, thus confirming the preclinical toxicity data. In addition to N-9, lemon and lime juices have been proposed and used as contraceptives and were recently shown to exhibit in vitro activity against HIV-1. Therefore, we tested freshly prepared lemon juice, lime juice, and household vinegar (concentration = 100%) for HIV-1 efficacy and toxicity and for effect on beneficial Lactobacillus species. In all assays, the therapeutic index was <10, due to toxicity of the juices and vinegar to cells (mean TC50 of lemon juice = 5.6%, mean TC50 of lime juice = 4.9%, and mean TC50 of vinegar 0.1%). Ten percent lemon or lime juice were not toxic to beneficial Lactobacillus species, in contrast to 10% vinegar which was highly toxic. Our preclinical data indicate that candidate topical microbicides should be moved forward into clinical trials with caution. from 2005 International Meeting of The Institute of Human Virology Baltimore, USA, 29 August – 2 September 2005
Source: Retrovirology
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,890
OpenAlex ID: W1578514643