Antiviral activity of HIV type 1 protease inhibitors nelfinavir and indinavir in vivo is not influenced by P-glycoprotein activity on CD4 + T cells

Sanjay U.C. Sankatsing, Marion Cornelissen, Nico Kloosterboer, Kristel M.L. Crommentuyn, Tessa M. Bosch, Frederik P. Mul, Suzanne Jurriaans, Alwin D.R. Huitema, Jos H. Beijnen, Joep M.A. Lange, Jan M. Prins, Hanneke Schuitemaker

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

6 Citaten (Scopus)

Samenvatting

P-glycoprotein (P-gp) can compromise the antiretroviral effect of a protease inhibitor (PI)-containing regimen for HIV-1, but can also reduce HIV-1 replication. We studied the net effect of P-gp on the intracellular HIV-1 RNA and DNA load in vivo. CD4+ T cells were isolated from 27 HIV-1 patients (13 without and 14 with a PI-containing regimen) and subsequently sorted in CD45RO- (naive) and CD45RO+ (memory) subsets with either high (P-gphigh) or low (P-gplow) P-gp activity. Unspliced HIV-1 RNA and HIV-1 DNA load were determined. For each patient P-gphigh and P-gplow subsets were compared. In patients on a PI-containing regimen, intracellular unspliced HIV-1 RNA was significantly lower in P-gphigh-naive CD4+ cells compared to P-gplow-naive CD4+ cells (p = 0.04). The same trend was seen in naive CD4+ cells of treatment-naive patients. In both treated and untreated patients HIV-1 DNA levels were significantly lower in P-gp high than in P-gplow memory CD4+ cells (p = 0.02 and p = 0.04). High cellular P-gp activity coincided with a reduced intracellular HIV-1 load in vivo, both in therapy-naive and in PI-treated patients. Therefore we conclude that the potential efflux function of P-gp on PIs may be clinically less relevant than the effect of P-gp on intracellular HIV-1 replication.

Originele taal-2Engels
Pagina's (van-tot)19-27
Aantal pagina's9
TijdschriftAIDS Research and Human Retroviruses
Volume23
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - jan. 2007
Extern gepubliceerdJa

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