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Prevention of vaginal simian immunodeficiency virus transmission in macaques by postexposure prophylaxis with zidovudine, lamivudine and indinavir

Bourry, Oliviera,c,f; Brochard, Patriciac,f; Souquiere, Sandrineb; Makuwa, Mariab; Calvo, Julienc,f; Dereudre-Bosquet, Nathaliec,d; Martinon, Frédéricc,f; Benech, Henrie; Kazanji, Mirdadb,g; Le Grand, Rogerc,f

doi: 10.1097/QAD.0b013e328321302d
Basic Science

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 SIVmac251.

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 (4.5 mg/kg), 3TC (2.5 mg/kg) and IDV (20 mg/kg) twice daily or subcutaneous ZDV (4.5 mg/kg) and 3TC (2.5 mg/kg) twice daily, and a higher dose of IDV (60 mg/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.

aCentre de Primatologie, Centre International de Recherches Médicales de Franceville, Franceville, France

bService de Rétrovirologie, Centre International de Recherches Médicales de Franceville, Franceville, Gabon, France

cCEA, Division of Immunovirology, Institute of Emerging Diseases and Innovative Therapies (IMETI), DSV, Fontenay aux Roses, France

dSPIBIO, Montigny-le, Bretonneux, France

eCEA, Service de Pharmacologie et d'Immunoanalyse, DSV/iBiTecS, CEA/Saclay, Gif-sur-Yvette, France

fUniv Paris-Sud 11, UMR E01, Orsay, France

gRéseau International des Instituts Pasteur, Institut Pasteur, Paris, France.

Received 3 June, 2008

Revised 3 November, 2008

Accepted 7 November, 2008

Correspondence to Olivier Bourry, Service d'immuno-virologie, Commissariat à l'Energie Atomique, DSV/iMETI, 18 route du Panorama, 92265 Fontenay-aux-Roses Cedex, France. E-mail:

© 2009 Lippincott Williams & Wilkins, Inc.