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Letter to the Editor

P-Glycoprotein Expression by Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Patients Is Independent from Response to Highly Active Antiretroviral Therapy

Chiara Agrati, Fabrizio Poccia, Simone Topino, Pasquale Narciso, Cinzia Selva, Leopoldo Paolo Pucillo, Gianpiero D'Offizi, Guido Antonelli, Francesca Bellomi, Ombretta Turriziani, Federica Bambacioni
Chiara Agrati
National Institute for Infectious Disease  “L. Spallanzani”—IRCCS Rome, Italy
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Fabrizio Poccia
National Institute for Infectious Disease  “L. Spallanzani”—IRCCS Rome, Italy
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Simone Topino
National Institute for Infectious Disease  “L. Spallanzani”—IRCCS Rome, Italy
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Pasquale Narciso
National Institute for Infectious Disease  “L. Spallanzani”—IRCCS Rome, Italy
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Cinzia Selva
National Institute for Infectious Disease  “L. Spallanzani”—IRCCS Rome, Italy
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Leopoldo Paolo Pucillo
National Institute for Infectious Disease  “L. Spallanzani”—IRCCS Rome, Italy
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Gianpiero D'Offizi
National Institute for Infectious Disease  “L. Spallanzani”—IRCCS Rome, Italy
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  • For correspondence: gdoffizi@inmi.it
Guido Antonelli
Department of Experimental Medicine  and Pathology Virology Section University of Rome La Sapienza Rome, Italy
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Francesca Bellomi
Department of Experimental Medicine  and Pathology Virology Section University of Rome La Sapienza Rome, Italy
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Ombretta Turriziani
Department of Experimental Medicine  and Pathology Virology Section University of Rome La Sapienza Rome, Italy
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Federica Bambacioni
Libera Università “Campus Biomedico” Rome, Italy
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DOI: 10.1128/CDLI.10.1.191-192.2003
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During the last few years, highly active antiretroviral therapy has considerably reduced human immunodeficiency virus (HIV) disease progression (11). However, the treatment outcome is not always satisfactory (7). This can depend on different virological, immunological, behavioral, or pharmacological factors (5). In the framework of aspects, the interaction between P-glycoprotein (P-gp) and antiretroviral drugs has been evidenced (8, 13, 15). P-gp is a transmembrane phosphoglycoprotein belonging to the ATP-binding cassette superfamily that is able to transport several substrates through the cell membrane acting as a cationic pump (2, 3, 4, 6, 9, 14). Specifically, studies on protease inhibitors (PI) have evidenced that the transporter activity of P-gp may contribute to the reduced bioavailability of these drugs, which can act as substrates for P-gp (4, 15, 16). However, the influence of HIV infection on P-gp expression is still a matter of debate (1, 9), and as yet, no data are available on the effects of highly active antiretroviral therapy on its expression.

The intensity of P-gp expression on peripheral blood mononuclear cells (PBMC) from healthy donors is 1.8 ± 0.5, as indicated by an intensity index described below (see footnote to Table 1). Recently, it has been reported that P-gp expression on PBMC was reduced in HIV-positive (HIV+) persons when compared with that found in healthy donors (10). Using the same approach, we analyzed the influence of antiretroviral treatment and that of viral and immunological parameters on P-gp expression on PBMC from 18 HIV+ persons. We defined three groups (Table 1): (i) HIV+ patients naive for antiretroviral therapy (n = 5); (ii) HIV+ patients with a successful response to the therapy (n = 8); and (iii) HIV+ patients with failing virological response to the therapy (n = 5). Treatment protocols of all patients are reported in Table 1.

In this pilot study, the expression of P-gp in total PBMC, CD4+ T lymphocytes, and CD14+ monocytes from naive, responder, and nonresponder patients was analyzed by flow cytometry. The intensity of P-gp expression on total PBMC of HIV+ patients was very low (0.99 ± 0.12), confirming previous observations (10). Further analysis among CD4+ T cells and CD14+ monocytes showed a higher intensity of P-gp expression on CD14+ monocytes than in CD4+ T lymphocytes (2.2 ± 1.3 versus 1.04 ± 0.16 [P < 0.05]). To asses whether the lack of virological response to the therapy treatment may be correlated with a different intensity of P-gp expression on the cell surface, we compared P-gp expression in the three groups of HIV+ patients described above (naive, responder, and nonresponder). No differences among these groups were observed in P-gp expression on total PBMC (naive, 1.04 ± 0.02; responder, 1.00 ± 0.02; and nonresponder, 0.92 ± 0.10), CD4+ T lymphocytes (naive, 1.14 ± 0.05; responder, 1.02 ± 0.04; and nonresponder, 0.98 ± 0.11), and CD14+ monocytes (naive, 2.67 ± 0.90; responder, 2.16 ± 0.39; and nonresponder, 1.95 ± 0.36). The frequency of P-gp-positive cells was independent of both the viremia levels and the T-cell count, and no difference between patients treated with PI and patients naive for PI treatment was observed. Altogether, these observation indicate that differences in P-gp levels did not appear to determine virological responses to antiretroviral therapy.

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TABLE 1.

Analysis of clinical parameters and P-gp expression in total PBMC, CD4+ T lymphocytes, and CD14+ monocytes from HIV+ patientsa

  • Copyright © 2003 American Society for Microbiology

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P-Glycoprotein Expression by Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Patients Is Independent from Response to Highly Active Antiretroviral Therapy
Chiara Agrati, Fabrizio Poccia, Simone Topino, Pasquale Narciso, Cinzia Selva, Leopoldo Paolo Pucillo, Gianpiero D'Offizi, Guido Antonelli, Francesca Bellomi, Ombretta Turriziani, Federica Bambacioni
Clinical and Diagnostic Laboratory Immunology Jan 2003, 10 (1) 191-192; DOI: 10.1128/CDLI.10.1.191-192.2003

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P-Glycoprotein Expression by Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Patients Is Independent from Response to Highly Active Antiretroviral Therapy
Chiara Agrati, Fabrizio Poccia, Simone Topino, Pasquale Narciso, Cinzia Selva, Leopoldo Paolo Pucillo, Gianpiero D'Offizi, Guido Antonelli, Francesca Bellomi, Ombretta Turriziani, Federica Bambacioni
Clinical and Diagnostic Laboratory Immunology Jan 2003, 10 (1) 191-192; DOI: 10.1128/CDLI.10.1.191-192.2003
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