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Prevention of vaginal simian immunodeficiency virus transmission in macaques by postexposure prophylaxis with zidovudine, lamivudine and indinavir.
- Source :
-
AIDS (London, England) [AIDS] 2009 Feb 20; Vol. 23 (4), pp. 447-54. - Publication Year :
- 2009
-
Abstract
- Objective: To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV), after vaginal exposure to HIV.<br />Design: : Experimental intravaginal exposure of female cynomolgus macaques to SIVmac251.<br />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.<br />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.<br />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.
- Subjects :
- Administration, Oral
Animals
Anti-HIV Agents blood
Antiretroviral Therapy, Highly Active
CD4 Lymphocyte Count
Disease Models, Animal
Drug Evaluation, Preclinical methods
Female
Indinavir blood
Indinavir therapeutic use
Injections, Subcutaneous
Lamivudine blood
Lamivudine therapeutic use
Macaca fascicularis
Sexually Transmitted Diseases, Viral immunology
Sexually Transmitted Diseases, Viral virology
Simian Acquired Immunodeficiency Syndrome immunology
Simian Acquired Immunodeficiency Syndrome transmission
Simian Acquired Immunodeficiency Syndrome virology
Vagina virology
Viral Load
Viremia prevention & control
Zidovudine blood
Zidovudine therapeutic use
Anti-HIV Agents therapeutic use
Sexually Transmitted Diseases, Viral prevention & control
Simian Acquired Immunodeficiency Syndrome prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5571
- Volume :
- 23
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- AIDS (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 19240457
- Full Text :
- https://doi.org/10.1097/QAD.0b013e328321302d