AEGiS-15IAC: P-glycoprotein function on CD4+ T-cells has no effect on the intracellular HIV-1 RNA load in HIV-1 infected patients.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

P-glycoprotein function on CD4+ T-cells has no effect on the intracellular HIV-1 RNA load in HIV-1 infected patients.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10135)

Prins JM, Sankatsing SU, Cornelissen M, Kloosterboer N, Crommentuyn K, Jurriaans S, Huitema A, Beijnen J, Lange JM, Schuitemaker H
International Antiviral Therapy Evaluation Center, Amsterdam, Netherlands

BACKGROUND: The drug transporter P-glycoprotein (P-gp) can counteract uptake of protease inhibitors (PIs) from the gut and reduces intracellular accumulation of PIs, which could limit antiretroviral effect of a PI containing regimen for HIV-1. However, P-gp expression on T cells can reduce HIV-1 replication. Here we studied the net effect of P-gp on intracellular HIV-1 RNA load in vivo.

METHODS: From 27 HIV-1 patients (13 without therapy and 14 with a PI containing regimen) a 50-mL blood sample was taken. CD4+ cells were isolated and subsequently sorted in naïve (CD45RO-) and memory (CD45RO+) subsets with either high P-gp activity (P-gpH) or low Pgp activity (P-gpL). In these subsets intracellular unspliced HIV-1 RNA load was measured using a quantitative real-time RT-PCR, as a measure for HIV-1 replication. HIV-1 RNA load in P-gpH and P-gpL subsets were compared in each patient and differences between the groups statistically tested with the Wilcoxon test.

RESULTS: In therapy naïve patients median intracellular HIV-1 RNA load in P-gpH and P-gpL naïve CD4+ T cells was log 1.0 (IQR 0.7-2.8) and log 1.4 (0.8-3.1) copies/104 cells, respectively (p=0.09), and median intracellular RNA in P-gpH and P-gpL memory cells was log 2.1 (0.7-3.2) and log 2.1 (1.2-3.1), respectively (p=0.31). In patients on therapy the median intracellular RNA in P-gpH and P-gpL naïve cells was log 0.7 (0.7-0.9) and log 1.1 (0.7-1.9), respectively (p=0.04), and the median intracellular RNA in P-gpH and P-gpL memory cells was log 1.1 (0.7-1.6) and log 1.5 (1.0-2.3), respectively(p=0.14).

CONCLUSION: There was no significant difference in intracellular HIV-1 RNA load in naïve and memory P-gpH and P-gpL CD4+ cells. The observation that in PI-treated patients the intracellular HIV-1 RNA load appeared to be lower in P-gpH cells warrants further investigation, and suggests that a lowering effect of P-gp on intracellular PI concentrations is not likely to be clinically relevant.

Keywords: AEGIS, HIV-1, Antigens, CD4, T-Lymphocytes, CD4-Positive T-Lymphocytes, Antigens, CD45, RNA, Viral, Cytoplasm, RNA, Virus Replication, Humans, physiology, immunology, virology

040711
A10135