Prevention of vaginal simian immunodeficiency virus transmission in macaques by postexposure prophylaxis with zidovudine, lamivudine and indinavir
| Autor: | Patricia Brochard, Roger Le Grand, Henri Benech, Mirdad Kazanji, Sandrine Souquière, Nathalie Dereudre-Bosquet, Frédéric Martinon, Olivier Bourry, Maria Makuwa, Julien Calvo |
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| Rok vydání: | 2009 |
| Předmět: |
genetic structures
Anti-HIV Agents Injections Subcutaneous viruses animal diseases Immunology Drug Evaluation Preclinical Simian Acquired Immunodeficiency Syndrome Administration Oral Indinavir Biology medicine.disease_cause Zidovudine immune system diseases Antiretroviral Therapy Highly Active medicine Animals Immunology and Allergy Viremia Sida Reverse-transcriptase inhibitor virus diseases Lamivudine Sexually Transmitted Diseases Viral Viral Load Simian immunodeficiency virus biology.organism_classification Virology CD4 Lymphocyte Count Disease Models Animal Macaca fascicularis Infectious Diseases medicine.anatomical_structure Vagina Female Viral load medicine.drug |
| Zdroj: | AIDS. 23:447-454 |
| ISSN: | 0269-9370 |
| DOI: | 10.1097/qad.0b013e328321302d |
| Popis: | To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV), after vaginal exposure to HIV.: Experimental intravaginal exposure of female cynomolgus macaques to SIVmac251.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.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.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. |
| Databáze: | OpenAIRE |
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