Antiviral Activity of HIV Type 1 Protease Inhibitors Nelfinavir and Indinavir in Vivo Is Not Influenced by P-Glycoprotein Activity on CD4+ T Cells

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-gphigh than in P-gplow memory CD4+ cells (p = 0.02 and p = 0.04). High cellular P-gp acti...