{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:22:51Z","timestamp":1790230971680,"version":"4.1.0"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T00:00:00Z","timestamp":1349049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nelfinavir has anti-inflammatory effects directly upon human macrophages independent of antiviral activity.<\/jats:p><jats:p>The HIV-1 PI NFV has off-target effects upon host enzymes, including inhibition of the 20S proteasome, resulting in activation of PP1. HIV-1-associated monocyte\/macrophage activation, in part a result of systemically elevated levels of microbial products including LPS, is associated with risk of mortality, independent of viremia or CD4 T cell loss. This study tested the hypothesis that activation of protein phosphatases by NFV would reduce activation of monocytes\/macrophages through dephosphorylation of signal transduction proteins. NFV uniquely blocked LPS-induced production by human monocyte-derived macrophages of the inflammatory cytokines TNF and IL-6, as well as sCD14. Although NFV failed to modulate NF-\u03baB, NFV treatment reduced phosphorylation of AKT and MAPKs. Inhibition of PP2 with okadaic acid blocked the anti-inflammatory effect of NFV, whereas the PP1 inhibitor calyculin A failed to counter the anti-inflammatory effects of NFV. For in vivo studies, plasma sCD14 and LPS were monitored in a cohort of 31 pediatric HIV-1 patients for over 2 years of therapy. Therapy, including NFV, reduced sCD14 levels significantly compared with IDV or RTV, independent of \u0394LPS levels, VL, CD4 T cell frequency, or age. The hypothesis was supported as NFV induced activation of PP2 in macrophages, resulting in disruption of inflammatory cell signaling pathways. In vivo evidence supports that NFV may offer beneficial effects independent of antiviral activity by reducing severity of chronic innate immune activation in HIV-1 infection.<\/jats:p>","DOI":"10.1189\/jlb.0911447","type":"journal-article","created":{"date-parts":[[2012,7,12]],"date-time":"2012-07-12T05:12:28Z","timestamp":1342069948000},"page":"795-805","source":"Crossref","is-referenced-by-count":24,"title":["The HIV-1 protease inhibitor nelfinavir activates PP2 and inhibits MAPK signaling in macrophages: a pathway to reduce inflammation"],"prefix":"10.1093","volume":"92","author":[{"given":"Mark A","family":"Wallet","sequence":"first","affiliation":[{"name":"University of Florida, Department of Pathology, Immunology and Laboratory Medicine , Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M","family":"Reist","sequence":"additional","affiliation":[{"name":"University of Florida, Department of Pathology, Immunology and Laboratory Medicine , Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie C","family":"Williams","sequence":"additional","affiliation":[{"name":"University of Florida, Department of Pathology, Immunology and Laboratory Medicine , Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Appelberg","sequence":"additional","affiliation":[{"name":"University of Florida, Department of Pathology, Immunology and Laboratory Medicine , Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio L","family":"Guiulfo","sequence":"additional","affiliation":[{"name":"University of Florida, Department of Pathology, Immunology and Laboratory Medicine , Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent","family":"Gardner","sequence":"additional","affiliation":[{"name":"University of Florida, Department of Pathology, Immunology and Laboratory Medicine , Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W","family":"Sleasman","sequence":"additional","affiliation":[{"name":"University of South Florida, All Children\u02c8s Hospital, Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology , St. Petersburg, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen M","family":"Goodenow","sequence":"additional","affiliation":[{"name":"University of Florida, Department of Pathology, Immunology and Laboratory Medicine , Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,10,1]]},"reference":[{"key":"2023012312554988200_B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2009.10.002","article-title":"The development of antiretroviral therapy and its impact on the HIV-1\/AIDS pandemic","volume":"85","author":"Broder","year":"2010","journal-title":"Antiviral Res."},{"key":"2023012312554988200_B2","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1097\/QAD.0b013e328339e228","article-title":"Microbial translocation induces persistent macrophage activation unrelated to HIV-1 levels or T-cell activation following therapy","volume":"24","author":"Wallet","year":"2010","journal-title":"AIDS"},{"key":"2023012312554988200_B3","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/nm1511","article-title":"Microbial translocation is a cause of systemic immune activation in chronic HIV infection","volume":"12","author":"Brenchley","year":"2006","journal-title":"Nat. Med."},{"key":"2023012312554988200_B4","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jaci.2008.04.029","article-title":"Antiretroviral therapy corrects HIV-1-induced expansion of CD8+ CD45RA+ CD2 -) CD11a(bright) activated T cells","volume":"122","author":"Yin","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"2023012312554988200_B5","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1128\/CVI.00074-09","article-title":"Antiretroviral therapy restores diversity in the T-cell receptor V\u03b2 repertoire of CD4 T-cell subpopulations among human immunodeficiency virus type 1-infected children and adolescents","volume":"16","author":"Yin","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"2023012312554988200_B6","first-page":"118","article-title":"Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy","volume":"17","author":"Deeks","year":"2009","journal-title":"Top. HIV Med."},{"key":"2023012312554988200_B7","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1172\/JCI200421318","article-title":"The immune response to AIDS virus infection: good, bad, or both?","volume":"113","author":"Deeks","year":"2004","journal-title":"J. Clin. Invest."},{"key":"2023012312554988200_B8","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1086\/524143","article-title":"Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy","volume":"197","author":"Hunt","year":"2008","journal-title":"J. Infect. Dis."},{"key":"2023012312554988200_B9","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1086\/374786","article-title":"T cell activation is associated with lower CD4 + T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy","volume":"187","author":"Hunt","year":"2003","journal-title":"J. Infect. Dis."},{"key":"2023012312554988200_B10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1046\/j.1365-2249.1998.00464.x","article-title":"Early increase ofCD4+ CD45RA+ and CD4 + CD95- cells with conserved repertoire induced by anti-retroviral therapy in HIV-infected patients","volume":"111","author":"Silvestri","year":"1998","journal-title":"Clin. Exp. Immunol."},{"key":"2023012312554988200_B11","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/vim.1997.10.207","article-title":"Changes in CD8 cell subpopulations induced by antiretroviral therapy in human immunodeficiency virus infected patients","volume":"10","author":"Silvestri","year":"1997","journal-title":"Viral Immunol."},{"key":"2023012312554988200_B12","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1182\/blood.V92.6.2084.418k26_2084_2092","article-title":"Elevated levels of serum-soluble CD14 in human immunodeficiency virus type 1 (HIV-1) infection: correlation to disease progression and clinical events","volume":"92","author":"Lien","year":"1998","journal-title":"Blood"},{"key":"2023012312554988200_B13","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1365-2249.1994.tb05499.x","article-title":"Increased soluble CD14 serum levels and altered CD14 expression of peripheral blood monocytes in HIV-infected patients","volume":"98","author":"Nockher","year":"1994","journal-title":"Clin. Exp. Immunol."},{"key":"2023012312554988200_B14","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1097\/INF.0b013e31821d141e","article-title":"Increased microbial translocation in \u2264 180 days old perinatally human immunodeficiency virus-positive infants as compared with human immunodeficiency virus-exposed uninfected infants of similar age","volume":"30","author":"Papasavvas","year":"2011","journal-title":"Pediatr. Infect. Dis. J."},{"key":"2023012312554988200_B15","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1086\/323036","article-title":"Plasma levels of soluble CD14 and tumor necrosis factor-\u03b1 type II receptor correlate with cognitive dysfunction during human immunodeficiency virus type 1 infection","volume":"184","author":"Ryan","year":"2001","journal-title":"J. Infect. Dis."},{"key":"2023012312554988200_B16","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1086\/590504","article-title":"Osteopontin is increased in HIV-associated dementia","volume":"198","author":"Burdo","year":"2008","journal-title":"J. Infect. Dis."},{"key":"2023012312554988200_B17","doi-asserted-by":"crossref","first-page":"e1000842","DOI":"10.1371\/journal.ppat.1000842","article-title":"Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD163 levels in plasma","volume":"6","author":"Burdo","year":"2010","journal-title":"PLoS Pathog."},{"key":"2023012312554988200_B18","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/ana.410310402","article-title":"Cytokine expression in the brain during the acquired immunodeficiency syndrome","volume":"31","author":"Tyor","year":"1992","journal-title":"Ann. Neurol."},{"key":"2023012312554988200_B19","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1097\/00001756-199407000-00026","article-title":"Activation of microglia in HIV-1 infected brains is not dependent on the presence of HIV-1 antigens","volume":"5","author":"Weis","year":"1994","journal-title":"Neuroreport"},{"key":"2023012312554988200_B20","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.1365-2567.2009.03225.x","article-title":"Inflammation in neurodegenerative diseases","volume":"129","author":"Amor","year":"2010","journal-title":"Immunology"},{"key":"2023012312554988200_B21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11883-010-0089-4","article-title":"The spectrum of atherosclerotic coronary artery disease in HIV patients","volume":"12","author":"Hakeem","year":"2010","journal-title":"Curr. Atheroscler. Rep."},{"key":"2023012312554988200_B22","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s11904-010-0045-5","article-title":"Does antiretroviral therapy increase or decrease the risk of cardiovascular disease?","volume":"7","author":"Fichtenbaum","year":"2010","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"2023012312554988200_B23","doi-asserted-by":"crossref","first-page":"e203","DOI":"10.1371\/journal.pmed.0050203","article-title":"Inflammatory and coagulation biomarkers and mortality in patients with HIV infection","volume":"5","author":"Kuller","year":"2008","journal-title":"PLoS Med."},{"key":"2023012312554988200_B24","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1086\/652749","article-title":"Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection","volume":"201","author":"Neuhaus","year":"2010","journal-title":"J. Infect. Dis."},{"key":"2023012312554988200_B25","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/BF02696656","article-title":"Endothelial dysfunction in HIV infection","volume":"3","author":"Cotter","year":"2006","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"2023012312554988200_B26","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1016\/j.bcp.2006.06.029","article-title":"Inflammation and cancer: how hot is the link?","volume":"72","author":"Aggarwal","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"2023012312554988200_B27","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0065-230X(08)00409-0","article-title":"HIV induced AIDS and related cancers: chronic immune activation and future therapeutic strategies","volume":"101","author":"Cadogan","year":"2008","journal-title":"Adv. Cancer Res."},{"key":"2023012312554988200_B28","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.2741\/2784","article-title":"Nelfinavir monotherapy increases naive T-cell numbers in HIV-negative healthy young adults","volume":"13","author":"Rizza","year":"2008","journal-title":"Front. Biosci."},{"key":"2023012312554988200_B29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2174\/157340608783331443","article-title":"HIV protease inhibitors impact on apoptosis","volume":"4","author":"Rizza","year":"2008","journal-title":"Med. Chem."},{"key":"2023012312554988200_B30","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1182\/blood.V98.2.383","article-title":"The HIV protease inhibitor indinavir inhibits cell-cycle progression in vitro in lymphocytes of HIV-infected and uninfected individuals","volume":"98","author":"Chavan","year":"2001","journal-title":"Blood"},{"key":"2023012312554988200_B31","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1182\/blood.V94.3.1021.415k29_1021_1027","article-title":"Human immunodeficiency virus type 1 protease inhibitor modulates activation of peripheral blood CD4( + ) T cells and decreases their susceptibility to apoptosis in vitro and in vivo","volume":"94","author":"Sloand","year":"1999","journal-title":"Blood"},{"key":"2023012312554988200_B32","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1177\/135965350501000203","article-title":"The HIV protease inhibitors nelfinavir and saquinavir, but not a variety of HIV reverse transcriptase inhibitors, adversely affect human proteasome function","volume":"10","author":"Piccinini","year":"2005","journal-title":"Antivir. Ther."},{"key":"2023012312554988200_B33","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1349-7006.2005.00063.x","article-title":"HIV-1 protease inhibitor induces growth arrest and apoptosis of human prostate cancer LNCaP cells in vitro and in vivo in conjunction with blockade of androgen receptor STAT3 and AKT signaling","volume":"96","author":"Yang","year":"2005","journal-title":"Cancer Sci."},{"key":"2023012312554988200_B34","doi-asserted-by":"crossref","first-page":"799","DOI":"10.2174\/156800911796798913","article-title":"Bortezomib targets the caspase-like proteasome activity in cervical cancer cells, triggering apoptosis that can be enhanced by nelfinavir","volume":"11","author":"Bruning","year":"2011","journal-title":"Curr. Cancer Drug Targets"},{"key":"2023012312554988200_B35","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.bbrc.2008.07.033","article-title":"HIV-protease inhibitors block the enzymatic activity of purified Ste24p","volume":"374","author":"Hudon","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023012312554988200_B36","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/ijc.25550","article-title":"Human immunodeficiency virus protease inhibitors reduce the growth of human tumors via a proteasome-independent block of angiogenesis and matrix metalloproteinases","volume":"128","author":"Toschi","year":"2011","journal-title":"Int. J. Cancer"},{"key":"2023012312554988200_B37","doi-asserted-by":"crossref","first-page":"13120","DOI":"10.1073\/pnas.95.22.13120","article-title":"An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses","volume":"95","author":"Andr\u00e9","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023012312554988200_B38","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S1470-2045(08)70334-6","article-title":"Anti-HIV drugs for cancer therapeutics: back to the future?","volume":"10","author":"Chow","year":"2009","journal-title":"Lancet Oncol."},{"key":"2023012312554988200_B39","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1177\/135965350701200407","article-title":"Some HIV antiretrovirals increase oxidative stress and alter chemokine, cytokine or adiponectin production in human adipocytes and macrophages","volume":"12","author":"Lagathu","year":"2007","journal-title":"Antivir Ther."},{"key":"2023012312554988200_B40","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1194\/jlr.M000869","article-title":"Glyceroneogenesis is inhibited through HIV protease inhibitor-induced inflammation in human subcutaneous but not visceral adipose tissue","volume":"52","author":"Leroyer","year":"2011","journal-title":"J. Lipid Res."},{"key":"2023012312554988200_B41","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1089\/aid.2006.0084","article-title":"HIV protease inhibitors selectively induce gene expression alterations associated with reduced calcium deposition in primary human osteoblasts","volume":"23","author":"Malizia","year":"2007","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"2023012312554988200_B42","doi-asserted-by":"crossref","first-page":"5183","DOI":"10.1158\/1078-0432.CCR-07-0161","article-title":"Nelfinavir, a lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo","volume":"13","author":"Gills","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"2023012312554988200_B43","doi-asserted-by":"crossref","first-page":"918","DOI":"10.2337\/diabetes.52.4.918","article-title":"Mechanisms for the deterioration in glucose tolerance associated with HIV protease inhibitor regimens","volume":"52","author":"Woerle","year":"2003","journal-title":"Diabetes"},{"key":"2023012312554988200_B44","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/jac\/dkh013","article-title":"Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients","volume":"53","author":"Calza","year":"2004","journal-title":"J. Antimicrob. Chemother"},{"key":"2023012312554988200_B45","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1097\/00002030-200001070-00006","article-title":"Effect of ritonavir on lipids and post-heparin lipase activities in normal subjects","volume":"14","author":"Purnell","year":"2000","journal-title":"AIDS"},{"key":"2023012312554988200_B46","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1097\/00002030-200411050-00005","article-title":"The effects of HIV protease inhibitors atazanavir and lopinavir\/ritonavir on insulin sensitivity in HIV-seronegative healthy adults","volume":"18","author":"Noor","year":"2004","journal-title":"AIDS"},{"key":"2023012312554988200_B47","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1124\/mol.104.010165","article-title":"Endoplasmic reticulum stress links dyslipidemia to inhibition of proteasome activity and glucose transport by HIV protease inhibitors","volume":"67","author":"Parker","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"2023012312554988200_B48","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1593\/neo.07124","article-title":"The HIV protease inhibitor nelfinavir downregulates Akt phosphorylation by inhibiting proteasomal activity and inducing the unfolded protein response","volume":"9","author":"Gupta","year":"2007","journal-title":"Neoplasia"},{"key":"2023012312554988200_B49","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1084\/jem.167.4.1428","article-title":"Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes","volume":"167","author":"Gendelman","year":"1988","journal-title":"J. Exp. Med."},{"key":"2023012312554988200_B50","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1074\/jbc.272.2.843","article-title":"Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate","volume":"272","author":"Huyer","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2023012312554988200_B51","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/0076-6879(91)01043-2","article-title":"Use of vanadate as protein-phosphotyrosine phosphatase inhibitor","volume":"201","author":"Gordon","year":"1991","journal-title":"Methods Enzymol."},{"key":"2023012312554988200_B52","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2004-0274","article-title":"Two-year clinical and immune outcomes in human immunodeficiency virus-infected children who reconstitute CD4 T cells without control of viral replication after combination antiretroviral therapy","volume":"114","author":"Ghaffari","year":"2004","journal-title":"Pediatrics"},{"key":"2023012312554988200_B53","doi-asserted-by":"crossref","DOI":"10.1086\/318538","article-title":"Human immunodeficiency virus type 1 protease genotype predicts immune and viral responses to combination therapy with protease inhibitors (PIs) in PI-naive patients","volume":"183","author":"Perez","year":"2001","journal-title":"J. Infect. Dis."},{"key":"2023012312554988200_B54","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1097\/QAD.0b013e32832e0599","article-title":"Genetic determinants in HIV-1 Gag and Env V3 are related to viral response to combination antiretroviral therapy with a protease inhibitor","volume":"23","author":"Ho","year":"2009","journal-title":"AIDS"},{"key":"2023012312554988200_B55","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1128\/CDLI.7.4.714-716.2000","article-title":"Viability and functional activity of cryopreserved mononuclear cells","volume":"7","author":"Weinberg","year":"2000","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"2023012312554988200_B56","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1128\/CVI.00342-08","article-title":"Optimization and limitations of use of cryopreserved peripheral blood mononuclear cells for functional and phenotypic T-cell characterization","volume":"16","author":"Weinberg","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"2023012312554988200_B57","volume-title":"ACTG\/IMPAACT Laboratory Manual.","year":"2009"},{"key":"2023012312554988200_B58","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1097\/00002030-200207050-00004","article-title":"Virologic response to nelfinavir-based regimens: pharmacokinetics and drug resistance mutations (VIRAPHAR study)","volume":"16","author":"Pellegrin","year":"2002","journal-title":"AIDS"},{"key":"2023012312554988200_B59","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1097\/COH.0b013e3282f82bf1","article-title":"Differences in the pharmacokinetics of protease inhibitors between healthy volunteers and HIV-infected persons","volume":"3","author":"Dickinson","year":"2008","journal-title":"Curr. Opin. HIV AIDS"},{"key":"2023012312554988200_B60","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1310\/RRX7-49ME-27V7-MWWV","article-title":"Pharmacokinetic characterization of different dose combinations of coadministered tipranavir and ritonavir in healthy volunteers","volume":"5","author":"MacGregor","year":"2004","journal-title":"HIV Clin. Trials"},{"key":"2023012312554988200_B61","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1128\/AAC.41.5.898","article-title":"Multiple-dose pharmacokinetics of ritonavir in human immunodeficiency virus-infected subjects","volume":"41","author":"Hsu","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"2023012312554988200_B62","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/00002030-199605000-00006","article-title":"A 24-week open-label phase I\/II evaluation of the HIV protease inhibitor MK-639 (indinavir)","volume":"10","author":"Stein","year":"1996","journal-title":"AIDS"},{"key":"2023012312554988200_B63","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/nri1184","article-title":"Signalling pathways of the TNF superfamily: a double-edged sword","volume":"3","author":"Aggarwal","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2023012312554988200_B64","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1152\/physrev.2001.81.2.807","article-title":"Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation","volume":"81","author":"Kyriakis","year":"2001","journal-title":"Physiol. Rev."},{"issue":"Suppl. 3","key":"2023012312554988200_B65","doi-asserted-by":"crossref","first-page":"iii70","DOI":"10.1136\/ard.2008.098459","article-title":"The PI3K\/Akt\/mTOR pathway in innate immune cells: emerging therapeutic applications","volume":"67","author":"Weichhart","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"2023012312554988200_B66","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1248\/bpb.30.1617","article-title":"Role of phosphoinositide 3-kinase in innate immunity","volume":"30","author":"Hazeki","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"2023012312554988200_B67","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1182\/blood-2003-12-4302","article-title":"Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K\/Akt pathway and of I\u03baB kinase activity","volume":"104","author":"Bhattacharyya","year":"2004","journal-title":"Blood"},{"key":"2023012312554988200_B68","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1182\/blood-2006-04-017368","article-title":"Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-\u03baB activation in dendritic cells","volume":"109","author":"Sen","year":"2007","journal-title":"Blood"},{"key":"2023012312554988200_B69","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1093\/infdis\/jiq118","article-title":"Plasma levels of soluble CD14 independently predict mortality in HIV infection","volume":"203","author":"Sandler","year":"2011","journal-title":"J. Infect. Dis."},{"key":"2023012312554988200_B70","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4161\/auto.5224","article-title":"Nelfinavir, a new anti-cancer drug with pleiotropic effects and many paths to autophagy","volume":"4","author":"Gills","year":"2008","journal-title":"Autophagy"},{"key":"2023012312554988200_B71","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1165\/ajrcmb.20.4.3420","article-title":"Both Erk and p38 kinases are necessary for cytokine gene transcription","volume":"20","author":"Carter","year":"1999","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2023012312554988200_B72","doi-asserted-by":"crossref","first-page":"15029","DOI":"10.1021\/bi035701y","article-title":"Secondary mutations M36I and A71V in the human immunodeficiency virus type 1 protease can provide an advantage for the emergence of the primary mutation D30N","volume":"42","author":"Clemente","year":"2003","journal-title":"Biochemistry"},{"key":"2023012312554988200_B73","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1086\/515312","article-title":"A preliminary evaluation of nelfinavir mesylate, an inhibitor of human immunodeficiency virus (HIV)-1 protease, to treat HIV infection","volume":"177","author":"Markowitz","year":"1998","journal-title":"J. Infect. Dis."},{"key":"2023012312554988200_B74","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1200\/JCO.2007.15.2355","article-title":"Phase I trial of the human immunodeficiency virus protease inhibitor nelfinavir and chemoradiation for locally advanced pancreatic cancer","volume":"26","author":"Brunner","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"2023012312554988200_B75","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.2165\/00003495-200565150-00015","article-title":"Nelfinavir: a review of its use in the management of HIV infection","volume":"65","author":"Perry","year":"2005","journal-title":"Drugs"},{"key":"2023012312554988200_B76","volume-title":"Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents.","year":"2011"},{"key":"2023012312554988200_B77","doi-asserted-by":"crossref","first-page":"8256","DOI":"10.1158\/0008-5472.CAN-05-1220","article-title":"HIV protease inhibitors block Akt signaling and radiosensitize tumor cells both in vitro and in vivo","volume":"65","author":"Gupta","year":"2005","journal-title":"Cancer Res."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1189%2Fjlb.0911447","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/92\/4\/795\/48765462\/jlb0795.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/92\/4\/795\/48765462\/jlb0795.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T22:45:40Z","timestamp":1743720340000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/92\/4\/795\/6935993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,1]]},"references-count":77,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2012,10,1]]},"published-print":{"date-parts":[[2012,10,1]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.0911447","relation":{},"ISSN":["1938-3673","0741-5400"],"issn-type":[{"value":"1938-3673","type":"electronic"},{"value":"0741-5400","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,10]]},"published":{"date-parts":[[2012,10,1]]}}}