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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Prevention of vaginal simian immunodeficiency virus transmission in macaques by postexposure prophylaxis with zidovudine, lamivudine and indinavir
AIDS, Volume 23, No. 4, Year 2009
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Description
Objective: To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lamivudine(3TC)and indinavir(IDV), after vaginal exposure to HIV. Design: Experimental intravaginal exposure of female cynomolgus macaques to SIV-mac251. Methods: ZDV/3TC/IDV treatment was initiated 4 h after exposure and continued for 28 days. Groups of six animals received a placebo or a combination of oral ZDV (4.5mg/kg), 3TC (2.5mg/kg) and IDV (20mg/kg) twice daily or subcutaneous ZDV (4.5mg/kg) and 3TC (2.5mg/kg) twice daily, and a higher dose of IDV (60mg/kg) administered orally twice daily. Results: In the placebo group, all animals were infected. Antiretroviral association protected one of the six animals if all drugs were administered orally and four of the six animals if ZDV and 3TC were administered subcutaneously and IDV was given orally at triple dose. In infected animals, viremia was significantly delayed and lowered in treated animals than in animals given placebo, and high CD4 cell counts were maintained in the treated animals, at least in the medium term. Antiretroviral dosages made in macaques receiving the same treatments showed that protection efficacy could be linked to antiretroviral plasmatic concentration. Conclusion: This study shows, for the first time in macaques, that the postexposure prophylaxis recommended for humans may be effective after vaginal exposure. Improvements in pharmacokinetic parameters significantly increased treatment efficiency. © 2009 Wolters Kluwer Health|Lippincott Williams & Wilkins.
Authors & Co-Authors
Bourry, Olivier
Gabon, Franceville
Centre International de Recherches Medicales de Franceville
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
France, Gif-sur-yvette
Université Paris-saclay
France, Gif-sur-yvette
Institut Des Maladies Emergentes et Des Thérapies Innovantes
Brochard, Patricia
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
France, Gif-sur-yvette
Université Paris-saclay
Souquière, Sandrine
Gabon, Franceville
Centre International de Recherches Medicales de Franceville
Makuwa, Maria
Gabon, Franceville
Centre International de Recherches Medicales de Franceville
Calvo, Julien
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
France, Gif-sur-yvette
Université Paris-saclay
Dereudre-Bosquet, Nathalie
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
Martinon, Frédéric
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
France, Gif-sur-yvette
Université Paris-saclay
Bénech, Henri C.
France, Gif-sur-yvette
Service de Pharmacologie et D'immunoanalyse
Kazanji, Mirdad
Gabon, Franceville
Centre International de Recherches Medicales de Franceville
France, Paris
Institut Pasteur, Paris
Le-Grand, Roger
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
France, Gif-sur-yvette
Université Paris-saclay
Statistics
Citations: 33
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1097/QAD.0b013e328321302d
Research Areas
Health System And Policy
Infectious Diseases
Participants Gender
Female