Prevention of vaginal simian immunodeficiency virus transmission in macaques by postexposure prophylaxis with zidovudine, lamivudine and indinavir.
OBJECTIVE
To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV), after vaginal exposure to HIV.


METHODS
: 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.


CONCLUSIONS
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.
Bourry
Olivier
O
Centre de Primatologie, Centre International de Recherches Médicales de Franceville, Franceville, France. obourry@yahoo.fr
Brochard
Patricia
P
Souquiere
Sandrine
S
Makuwa
Maria
M
Calvo
Julien
J
Dereudre-Bosquet
Nathalie
N
Martinon
Frédéric
F
Benech
Henri
H
Kazanji
Mirdad
M
Le Grand
Roger
R
D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000097:blood / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D019469:Indinavir / Q000097:blood / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D019259:Lamivudine / Q000097:blood / Q000627:therapeutic use; D008252:Macaca fascicularis; D015229:Sexually Transmitted Diseases, Viral / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D014621:Vagina / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000517:prevention & control; D015215:Zidovudine / Q000097:blood / Q000627:therapeutic use
D019380:Anti-HIV Agents; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir