دورية أكاديمية
Antiviral activity of HIV type 1 protease inhibitors nelfinavir and indinavir in vivo is not influenced by P-glycoprotein activity on CD4+ T cells.
العنوان: | Antiviral activity of HIV type 1 protease inhibitors nelfinavir and indinavir in vivo is not influenced by P-glycoprotein activity on CD4+ T cells. |
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المؤلفون: | Sankatsing SU; International Antiviral Therapy Evaluation Center, Amsterdam, The Netherlands. s.u.sankatsing@amc.uva.nl, Cornelissen M, Kloosterboer N, Crommentuyn KM, Bosch TM, Mul FP, Jurriaans S, Huitema AD, Beijnen JH, Lange JM, Prins JM, Schuitemaker H |
المصدر: | AIDS research and human retroviruses [AIDS Res Hum Retroviruses] 2007 Jan; Vol. 23 (1), pp. 19-27. |
نوع المنشور: | Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Mary Ann Liebert Country of Publication: United States NLM ID: 8709376 Publication Model: Print Cited Medium: Print ISSN: 0889-2229 (Print) Linking ISSN: 08892229 NLM ISO Abbreviation: AIDS Res Hum Retroviruses Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Larchmont, NY : Mary Ann Liebert Original Publication: [New York] : Mary Ann Liebert, [c1987- |
مواضيع طبية MeSH: | HIV-1*, ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism , HIV Protease Inhibitors/*pharmacology , Indinavir/*pharmacology , Nelfinavir/*pharmacology, Adult ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/metabolism ; DNA, Viral/blood ; Humans ; Leukocytes, Mononuclear/metabolism ; Middle Aged ; Polymerase Chain Reaction ; RNA, Viral/blood ; Viral Load |
مستخلص: | 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-gp(high)) or low (P-gp(low)) P-gp activity. Unspliced HIV-1 RNA and HIV-1 DNA load were determined. For each patient P-gp(high) and P-gp(low) subsets were compared. In patients on a PI-containing regimen, intracellular unspliced HIV-1 RNA was significantly lower in P-gp(high)-naive CD4(+) cells compared to P-gp(low)-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-gp(low) 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. |
المشرفين على المادة: | 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) 0 (DNA, Viral) 0 (HIV Protease Inhibitors) 0 (RNA, Viral) 5W6YA9PKKH (Indinavir) HO3OGH5D7I (Nelfinavir) |
تواريخ الأحداث: | Date Created: 20070201 Date Completed: 20070411 Latest Revision: 20181201 |
رمز التحديث: | 20231215 |
DOI: | 10.1089/aid.2006.0027 |
PMID: | 17263628 |
قاعدة البيانات: | MEDLINE |
تدمد: | 0889-2229 |
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DOI: | 10.1089/aid.2006.0027 |