[Evaluation of the effect of early and massive tritherapy on the expression of cellular factors potentially implicated in antiretroviral therapy resistance].
Treatment of the human immunodeficiency virus (HIV) is restricted by therapeutic escape. The biological mechanisms of this chemoresistance rely notably on the modulation of cell kinase and P-glycoprotein (P-gp) expression. In this study, we investigated, in cynomolgus macaques, the roles of SHIV89.6P infection and of HAART in the mRNA expression of these cell factors. SHIV infection, or associated pathophysiological disorders, increase both thymidine kinase and thymidylate kinase mRNA expression and decrease those of P-gp. On the other hand, the expression of other cell kinases is not modulated. In parallel, HAART accentuates the decrease of P-gp expression and attenuates the increase of kinase expression. On the whole, such metabolic disorders, evidenced herein an animal model of HIV infection, could be involved in HIV-infected patients.
Jorajuria
S
S
Service de neurovirologie, DSV/DRM, CEA, CRSSA, Fontenay-aux-Roses, France.
Clayette
P
P
Dereuddre-Bosquet
N
N
Larghero
J
J
Thiebot
H
H
Neildez
O
O
Vaslin
B
B
Le Grand
R
R
Dormont
D
D
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D015870:Gene Expression / Q000187:drug effects*; D019469:Indinavir / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008252:Macaca fascicularis; D008297:Male; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D013937:Thymidine Kinase / Q000235:genetics; D015215:Zidovudine / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019380:Anti-HIV Agents; D012333:RNA, Messenger; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D013937:Thymidine Kinase; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase