P-glycoprotein in blood CD4 cells of HIV-1-infected patients treated with protease inhibitors.
OBJECTIVE
Many factors are involved in the virological failure of antiretroviral treatments such as low pharmacological plasma levels of drugs, poor adherence to therapy and emergence of viral resistance. P-glycoprotein (P-gp) has been demonstrated to play a role in multidrug resistance in the therapy of solid tumours, haematological malignancies and Plasmodium falciparum infection. HIV-1 protease inhibitors (PIs) have been described to be substrates of P-gp. In vitro and in vivo studies performed in mice have demonstrated that P-gp may affect the oral bioavailability and intracellular accumulation of PIs. P-gps have been detected on peripheral CD4 blood cells in HIV-1-infected, but antiretroviral-naive patients.


METHODS
We quantified P-gp expression and performed functional tests of P-gp activity in the CD4 cells in HIV-1-infected patients, with and without virological failure, treated with PIs, and in healthy patients (control group).


RESULTS
Out of the 18 HIV-infected patients studied, P-gp expression and function were found in the CD4 cells of six patients (four of 10 without, and two of eight with virological failure). Out of the 43 healthy patients studied, P-gp expression and function were found in the CD4 cells of 11 patients (26%). We found P-gp in peripheral CD4 cells of patients treated with PIs, with and without virological failure, within the same frequency than in antiretroviral naive patients or than in non HIV-infected patients.


CONCLUSIONS
P-gp expression in peripheral CD4 blood cells does not seem to be enhanced by PI treatment and does not seem to be linked particularly to virological failures. These facts do not preclude of the role of P-gp on PI absorption or efficacy in other compartments of the body such as gut, lymph nodes or brain in HIV-1 PI-treated patients.
Bossi
P
P
Department of Virology, Pitié-Salpêtrière Hospital, 47-83 Bd de l'Hôpital, Paris, France. philippebossi@psalp-hop-paris.fr
Legrand
O
O
Faussat
A-M
AM
Legrand
M
M
Bricaire
F
F
Marie
J-P
JP
Agut
H
H
Diquet
B
B
Katlama
C
C
Huraux
J-M
JM
Calvez
V
V
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D009154:Mutation; D012367:RNA, Viral / Q000032:analysis; D019562:Viral Load
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D016333:HIV Protease