Imperial College London

ProfessorRobinShattock

Faculty of MedicineDepartment of Infectious Disease

Chair in Mucosal Infection and Immunity
 
 
 
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Contact

 

+44 (0)20 7594 5206r.shattock

 
 
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Location

 

453Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cranage:2008:10.1371/journal.pmed.0050157,
author = {Cranage, M and Sharpe, S and Herrera, C and Cope, A and Dennis, M and Berry, N and Ham, C and Heeney, J and Rezk, N and Kashuba, A and Anton, P and McGowan, I and Shattock, R},
doi = {10.1371/journal.pmed.0050157},
journal = {PLoS Medicine},
title = {Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel},
url = {http://dx.doi.org/10.1371/journal.pmed.0050157},
volume = {5},
year = {2008}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - BACKGROUND: The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV) drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT) inhibitor tenofovir (PMPA, 9-[(R)-2-(phosphonomethoxy) propyl] adenine monohydrate), a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV) in a well-established and standardised macaque model. METHODS AND FINDINGS: A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50) of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC), quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA) load by sensitive quantitative competitive (qc) RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test) wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from
AU - Cranage,M
AU - Sharpe,S
AU - Herrera,C
AU - Cope,A
AU - Dennis,M
AU - Berry,N
AU - Ham,C
AU - Heeney,J
AU - Rezk,N
AU - Kashuba,A
AU - Anton,P
AU - McGowan,I
AU - Shattock,R
DO - 10.1371/journal.pmed.0050157
PY - 2008///
SN - 1549-1277
TI - Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel
T2 - PLoS Medicine
UR - http://dx.doi.org/10.1371/journal.pmed.0050157
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18684007
UR - http://hdl.handle.net/10044/1/70680
VL - 5
ER -