3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

DEVELOPMENT OF A HUMAN PENILE TISSUE EXPLANT MODEL TO EVALUATE SAFETY AND EFFICACY OF MICROBICIDE CANDIDATES

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. MoPp0104

Shattock R., Fischetti L., Fletcher P., Hu Q., Harman S., Mesquita P.
St George's Hospital Medical School, London, United Kingdom

BACKGROUND: While much has been learnt about vaginal and/or rectal transmission, factors governing events between exposure of male genital mucosal surfaces and establishment of clinical infection are poorly understood and little is known about the safety and efficacy of potential microbicides for male genital tissue. However, candidate vaginal microbicides may also provide protection to male partners of HIV-1 infected women. Here we present a novel penile tissue explant model to characterise the mechanisms of HIV-1 infection of male genital tissue and evaluate candidate microbicides.

METHODS: Male genital tissue was obtained, with consent, from gender reassignment and other surgical procedures. Optimal mucosal explant culture conditions have been determined for glans, urethra (high and low) and transformation zone. In vitro HIV-1 infection was evaluated by measurement of p24 release and proviral formation, furthermore microbicide biocompatibility was assessed by viability assay (MTT) and cytokine production.

RESULTS: We have examined the relative susceptibility of different tissue sites (glans, urethra (high and low) and transformation zone). Preliminary studies demonstrate that while all sites are susceptible to HIV-1 infection, glans tissue represents the most active site for viral replication. Blocking studies using co-receptor antagonists demonstrate CCR5 and CXCR4 as the predominant receptors for HIV-1 infection. Early studies of tissue compatibility demonstrate that while nonoxynol 9 and lemon juice are highly toxic for male genital tissue, a range of candidate microbicides show good tissue compatibility. Furthermore, the candidate NNRTI microbicide TMC-120 demonstrates efficient prevention of HIV-1 infection.

CONCLUSIONS: The described model may provide an important tool to aid understanding of the determinants of HIV-1 infection of male genital tissue, and may facilitate the successful development of safe and effective microbicides designed to protect both men and women.

Download PDF of this abstract.

050724
Prevention | MoPp0104 | Robin Shattock
10.8 261 10.8 Microbicides

Copyright © 2005 - International AIDS Society (IAS). All information and content relating to the abstracts from the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment, such as text, graphics, logos, button icons, images, audio clips, and software is protected by copyright. Permission is hereby granted for the non-commercial use or reproduction of the information on this web site, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.

AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2005. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2005. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Permission is hereby granted for the non-commercial use or reproduction of the information herein, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.