hiv protease inhibitors

Summary

Summary: Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.

Top Publications

  1. pmc Human immunodeficiency virus reverse transcriptase and protease sequence database
    Soo Yon Rhee
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
    Nucleic Acids Res 31:298-303. 2003
  2. ncbi A comparison study of multiple measures of adherence to HIV protease inhibitors
    H Liu
    Division of General Internal Medicine and Health Service Research, 911 Broxton Plaza, Room 102, Los Angeles, CA 90095 1736, USA
    Ann Intern Med 134:968-77. 2001
  3. ncbi 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
    Joell J Gills
    Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20889, USA
    Clin Cancer Res 13:5183-94. 2007
  4. pmc HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance
    Robert W Shafer
    Division of Infectious Diseases, Stanford University, Stanford, California, USA
    AIDS 21:215-23. 2007
  5. ncbi Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study
    Jean Michel Molina
    Department of Infectious Diseases, Saint Louis Hospital, AP HP, Paris University of Paris Diderot, Paris 7, France
    Lancet 372:646-55. 2008
  6. ncbi Effects of HIV protease inhibitor therapy on lipid metabolism
    David Y Hui
    Department of Pathology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267 0529, USA
    Prog Lipid Res 42:81-92. 2003
  7. pmc Virtual screening for HIV protease inhibitors: a comparison of AutoDock 4 and Vina
    Max W Chang
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
    PLoS ONE 5:e11955. 2010
  8. ncbi A semiempirical free energy force field with charge-based desolvation
    Ruth Huey
    Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92102, USA
    J Comput Chem 28:1145-52. 2007
  9. ncbi Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia
    S G Deeks
    University of California, San Francisco, and San Francisco General Hospital, USA
    N Engl J Med 344:472-80. 2001
  10. ncbi Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136
    Christine Katlama
    INSERM UMR S 943 and University Pierre and Marie Curie UPMC Paris VI, Paris, France
    AIDS 24:2365-74. 2010

Detail Information

Publications328 found, 100 shown here

  1. pmc Human immunodeficiency virus reverse transcriptase and protease sequence database
    Soo Yon Rhee
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
    Nucleic Acids Res 31:298-303. 2003
    ..Sequence data on two new molecular targets of HIV drug therapy--gp41 (cell fusion) and integrase--will be added to the database in 2003...
  2. ncbi A comparison study of multiple measures of adherence to HIV protease inhibitors
    H Liu
    Division of General Internal Medicine and Health Service Research, 911 Broxton Plaza, Room 102, Los Angeles, CA 90095 1736, USA
    Ann Intern Med 134:968-77. 2001
    Poor adherence to HIV protease inhibitors may compromise the effectiveness of treatment. Few studies have compared methods for measuring adherence or have related adherence measures to a clinical outcome.
  3. ncbi 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
    Joell J Gills
    Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20889, USA
    Clin Cancer Res 13:5183-94. 2007
    The development of new cancer drugs is slow and costly. HIV protease inhibitors are Food and Drug Administration approved for HIV patients...
  4. pmc HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance
    Robert W Shafer
    Division of Infectious Diseases, Stanford University, Stanford, California, USA
    AIDS 21:215-23. 2007
    ..However, such programs will not produce comparable estimates unless a standardized list of drug-resistance mutations is used to define transmitted resistance...
  5. ncbi Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study
    Jean Michel Molina
    Department of Infectious Diseases, Saint Louis Hospital, AP HP, Paris University of Paris Diderot, Paris 7, France
    Lancet 372:646-55. 2008
    ..We compared these two combinations directly in treatment-naive patients...
  6. ncbi Effects of HIV protease inhibitor therapy on lipid metabolism
    David Y Hui
    Department of Pathology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267 0529, USA
    Prog Lipid Res 42:81-92. 2003
    ..However, the benefits of HIV protease inhibitors are compromised by numerous undesirable side effects...
  7. pmc Virtual screening for HIV protease inhibitors: a comparison of AutoDock 4 and Vina
    Max W Chang
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
    PLoS ONE 5:e11955. 2010
    ..This study compares AutoDock 4 and AutoDock Vina in the context of virtual screening by using these programs to select compounds active against HIV protease...
  8. ncbi A semiempirical free energy force field with charge-based desolvation
    Ruth Huey
    Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92102, USA
    J Comput Chem 28:1145-52. 2007
    ..The force field shows improvement in redocking simulations over the previous AutoDock3 force field...
  9. ncbi Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia
    S G Deeks
    University of California, San Francisco, and San Francisco General Hospital, USA
    N Engl J Med 344:472-80. 2001
    ..In many patients with human immunodeficiency virus (HIV) infection, therapy with potent antiretroviral drugs does not result in complete suppression of HIV replication. The effect of cessation of therapy in these patients is unknown...
  10. ncbi Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136
    Christine Katlama
    INSERM UMR S 943 and University Pierre and Marie Curie UPMC Paris VI, Paris, France
    AIDS 24:2365-74. 2010
    ..Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs...
  11. ncbi Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy
    Miguel Goicoechea
    Antiviral Research Center, University of California, San Diego, 150 W Washington St, Ste 100, San Diego, CA 92103, USA
    J Infect Dis 197:102-8. 2008
    ....
  12. pmc Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance
    Christina M Marra
    Department of Neurology, University of Washington School of Medicine, Seattle, USA
    AIDS 23:1359-66. 2009
    ..To determine whether antiretroviral regimens with good central nervous system (CNS) penetration control HIV in cerebrospinal fluid (CSF) and improve cognition...
  13. ncbi Body composition changes after switching from protease inhibitors to raltegravir: SPIRAL-LIP substudy
    Adrian Curran
    Hospital Universitari Vall d Hebron, Universitat Autonoma de Barcelona, Infectious Diseases Department, Spain
    AIDS 26:475-81. 2012
    ..To compare 48-week changes in body fat distribution and bone mineral density (BMD) between patients switching from a ritonavir-boosted protease inhibitor (PI/r) to raltegravir (RAL) and patients continuing with PI/r...
  14. ncbi Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. International AIDS Society--USA Panel
    M S Hirsch
    Harvard Medical School, Boston, MA, USA
    JAMA 279:1984-91. 1998
    ..To review current knowledge of the biology and clinical implications of human immunodeficiency virus (HIV) resistance to antiretroviral drugs, describe assays for measuring resistance, and assess their use in clinical practice...
  15. pmc Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1
    Eric S Daar
    Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, 1124 West Carson Street, N 24, Torrance, CA 90502, USA
    Ann Intern Med 154:445-56. 2011
    ..Limited data compare once-daily options for initial therapy for HIV-1...
  16. ncbi HIV protease inhibitors activate the unfolded protein response in macrophages: implication for atherosclerosis and cardiovascular disease
    Huiping Zhou
    Department of Microbiology and Immunology, Virginia Commonwealth University, P O Box 980678, Richmond, VA 23298 0678, USA
    Mol Pharmacol 68:690-700. 2005
    ..Treatment of patients infected with HIV with HIV protease inhibitors is unfortunately associated with a number of clinically significant metabolic abnormalities and an ..
  17. ncbi Class of antiretroviral drugs and the risk of myocardial infarction
    Nina Friis-Møller
    University of Copenhagen, Copenhagen, Denmark
    N Engl J Med 356:1723-35. 2007
    ..We conducted a study to investigate the association of cumulative exposure to protease inhibitors and nonnucleoside reverse-transcriptase inhibitors with the risk of myocardial infarction...
  18. ncbi Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis
    Yuan Ren
    Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
    J Acquir Immune Defic Syndr 47:566-9. 2008
    ..We evaluated the effect of additional ritonavir on plasma lopinavir concentrations in HIV-infected children receiving rifampicin-based treatment for tuberculosis...
  19. ncbi Ritonavir-boosted atazanavir exposure is associated with an increased rate of renal stones compared with efavirenz, ritonavir-boosted lopinavir and ritonavir-boosted darunavir
    Neesha Rockwood
    Department of HIV Medicine, Chelsea and Westminster Hospital, London, UK
    AIDS 25:1671-3. 2011
    ..When choosing a boosted protease inhibitor, ATZ/r renal stones should be considered as a potential comorbidity...
  20. ncbi High incidence of renal stones among HIV-infected patients on ritonavir-boosted atazanavir than in those receiving other protease inhibitor-containing antiretroviral therapy
    Yohei Hamada
    AIDS Clinical Center, National Center for Global Health and Medicine, 1 21 1 Toyama, Shinjuku ku, Tokyo, Japan
    Clin Infect Dis 55:1262-9. 2012
    ..Little information is available on the incidence of renal stones with ritonavir-boosted atazanavir (ATV/r) use...
  21. ncbi Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study
    Nina Friis-Møller
    DAD Coordinating Centre, Copenhagen HIV Programme, Hvidovre University Hospital, Copenhagen, Denmark
    AIDS 17:1179-93. 2003
    ..To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies...
  22. ncbi Antiviral drugs in current clinical use
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    J Clin Virol 30:115-33. 2004
    ....
  23. ncbi Premature senescence of vascular cells is induced by HIV protease inhibitors: implication of prelamin A and reversion by statin
    Chloé Lefèvre
    Faculté deMédecine Saint Antoine, Institut National de la Santé et de la Recherche Scientifique, Saint Antoine Research Center, Unité Mixte de Recherche S 938, Paris, France
    Arterioscler Thromb Vasc Biol 30:2611-20. 2010
    ..To determine whether and how protease inhibitors (PIs) could affect vascular aging...
  24. ncbi Use of complementary and alternative therapies in HIV-infected patients
    J Duggan
    Department of Physiology and Molecular Medicine, Medical College of Ohio, Toledo, Ohio 43614 5804, USA
    AIDS Patient Care STDS 15:159-67. 2001
    ..Use of CAM remains widespread among patients with HIV infection even with the availability of effective, yet noncurative antiretroviral therapy and does not correlate with type of antiretroviral therapy used or clinical status...
  25. pmc Sex differences in lopinavir and ritonavir pharmacokinetics among HIV-infected women and men
    Obi C Umeh
    David Geffen School of Medicine at UCLA, Los Angeles, California, USA
    J Clin Pharmacol 51:1665-73. 2011
    ..Women had higher RTV AUC(0-12 h) and lower CL/F with both formulations. The mechanism of the sex difference in RTV CL/F warrants elucidation...
  26. ncbi Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial
    S Staszewski
    Klinikum der Johann Wolfgang Goethe Universitat, Zentrum der Inneren Medizin, Infektionsambulanz, Haus 68, Theodor Stern Kai 7, D 60596 Frankfurt, Germany
    JAMA 285:1155-63. 2001
    ..However, the role of abacavir in a triple nucleoside combination regimen has not been evaluated against a standard protease inhibitor-containing regimen for initial antiretroviral treatment...
  27. ncbi Rifamycin-resistant Mycobacterium tuberculosis in the highly active antiretroviral therapy era: a report of 3 relapses with acquired rifampin resistance following alternate-day rifabutin and boosted protease inhibitor therapy
    Elizabeth R Jenny-Avital
    Jacobi Medical Center, Administration for Children s Services Clinic, Bronx, New York 10461, USA
    Clin Infect Dis 48:1471-4. 2009
    ..Higher doses of rifabutin and a ritonavir-boosted HIV protease inhibitor as treatment for tuberculosis should be studied further...
  28. pmc Pharmacokinetics of darunavir/ritonavir and rifabutin coadministered in HIV-negative healthy volunteers
    Vanitha Sekar
    Tibotec, Inc, Yardley, Pennsylvania, USA
    Antimicrob Agents Chemother 54:4440-5. 2010
    ..Given the safety profile seen with the combination of RFB with a boosted protease inhibitor in this and other studies, it is not recommended to conduct further studies with this combination in healthy volunteers...
  29. pmc HIV-1 protease mutations and protease inhibitor cross-resistance
    Soo Yon Rhee
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California 94305, USA
    Antimicrob Agents Chemother 54:4253-61. 2010
    ....
  30. pmc HIV-1 Gag processing intermediates trans-dominantly interfere with HIV-1 infectivity
    Barbara Muller
    Department of Virology, Universitatsklinikum Heidelberg, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
    J Biol Chem 284:29692-703. 2009
    ..These effects are likely to be important for the strong activity of PI at concentrations achieved in vivo and also bear relevance for the mechanism of action of the antiviral drug bevirimat...
  31. ncbi HIV antiretroviral treatment alters adipokine expression and insulin sensitivity of adipose tissue in vitro and in vivo
    Claire Lagathu
    Inserm U 680 and IFR65, Universite Pierre et Marie Curie, Faculte de Medecine Saint Antoine, 27, rue Chaligny, 75571 Paris Cedex 12, France
    Biochimie 87:65-71. 2005
    ..Therefore, they could be involved in whole body insulin resistance and metabolic alterations in lipodystrophic HIV-1-infected patients...
  32. ncbi HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2)
    Anshul Gupta
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195 7610, USA
    J Pharmacol Exp Ther 310:334-41. 2004
    ..These results suggest that BCRP may play an important role in drug-drug interactions involving coadministration of the HPIs with drugs that are substrates of the transporter...
  33. ncbi Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1
    P Annaert
    Laboratory for Pharmacotechnology and Biopharmacy, Department of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Leuven, Belgium
    Xenobiotica 40:163-76. 2010
    ..The remarkably potent inhibition of OATP1B1 by lopinavir may explain some clinically relevant drug interactions between lopinavir and OATP1B substrates such as fexofenadine...
  34. ncbi Combination of protease inhibitors for the treatment of HIV-1-infected patients: a review of pharmacokinetics and clinical experience
    R P van Heeswijk
    Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands
    Antivir Ther 6:201-29. 2001
    ..This review covers combinations of saquinavir, indinavir, nelfinavir, amprenavir and lopinavir with different doses of ritonavir, as well as the combinations of saquinavir and indinavir with nelfinavir...
  35. ncbi Treatment outcomes of patients on second-line antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis
    Olawale Ajose
    Clinton Health Access Initiative, Dar es Salaam, Tanzania
    AIDS 26:929-38. 2012
    ..We carried out a systematic review in order to summarize reported rates and reasons for virological failure among people on second-line therapy in resource-limited settings...
  36. ncbi Mutational patterns in the frameshift-regulating site of HIV-1 selected by protease inhibitors
    Elena Knops
    Institute of Virology, University of Cologne, Fürst Pückler Str 56, 50935, Cologne, Germany
    Med Microbiol Immunol 201:213-8. 2012
    ..Additionally, Gag non-cleavage site mutations accumulated in PI-resistant HIV-1 isolates, but were not related to an increased frameshift efficiency...
  37. ncbi Factors associated with virological failure in HIV-1-infected patients receiving darunavir/ritonavir monotherapy
    Sidonie Lambert-Niclot
    Department of Virology and Infectious Diseases, AP HP, Pitie Salpetriere Hospital, INSERM U 943 and Pierre et Marie Curie University, Paris, France
    J Infect Dis 204:1211-6. 2011
    ..Our objective was to determine virological and clinical characteristics associated with virological failure in human immunodeficiency virus (HIV)-infected patients switching to darunavir/ritonavir (DRV/r) monotherapy...
  38. ncbi Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy
    Viviane D Lima
    BC Centre for Excellence in HIV AIDS, St Paul s Hospital, Vancouver, British Columbia, Canada
    AIDS 21:685-92. 2007
    ..To characterize the temporal changes in mortality and life expectancy among HIV-positive individuals initiating antiretroviral therapy in British Columbia, Canada, from 1993 to 2004...
  39. pmc Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers
    C J L la Porte
    Department of Clinical Pharmacy, University Medical Centre Nijmegen, Nijmegen University Centre for Infectious Diseases, Nijmegen, The Netherlands
    Antimicrob Agents Chemother 48:1553-60. 2004
    ..5 mg/liter (day 24) and was similar between the two arms. Adjusted-dose regimens of lopinavir-ritonavir in combination with therapeutic drug monitoring and monitoring of liver function may allow concomitant use of rifampin...
  40. ncbi Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir
    Christine Gutmann
    Cantonal Hospital St Gallen, St Gallen, Switzerland
    AIDS 24:2347-54. 2010
    ..Monotherapy with ritonavir-boosted lopinavir (LPV/r-MT) is the most widely studied strategy. However, efficacy of LPV/r-MT in compartments remains to be shown...
  41. ncbi Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV
    Federico Pulido
    Unidad HIV and Laboratorio de Microbiología Molecular, Hospital 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain
    AIDS 22:F1-9. 2008
    ..Prior attempts to reduce the number of drugs needed to maintain viral suppression in patients with suppressed HIV replication while receiving three antiretroviral drugs have been unsuccessful...
  42. ncbi The impact of HIV-protease inhibitors on opportunistic parasites
    Edoardo Pozio
    Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy
    Trends Parasitol 21:58-63. 2005
    ..of cell-mediated immunity induced by either non-nucleoside reverse transcriptase inhibitors or HIV protease inhibitors, in combination with at least two nucleoside reverse transcriptase inhibitors included in HAART, there is ..
  43. pmc Protease inhibitor resistance analysis in the MONARK trial comparing first-line lopinavir-ritonavir monotherapy to lopinavir-ritonavir plus zidovudine and lamivudine triple therapy
    Constance Delaugerre
    University Paris Descartes, EA 3620, Virology Department, Necker Hospital AP HP, Paris, France
    Antimicrob Agents Chemother 53:2934-9. 2009
    ..The mutation L76V may be considered in further studies of lopinavir resistance...
  44. pmc Polymorphism in Gag gene cleavage sites of HIV-1 non-B subtype and virological outcome of a first-line lopinavir/ritonavir single drug regimen
    Jade Ghosn
    Paris Descartes University, EA 3620, Necker University Hospital, Paris, France
    PLoS ONE 6:e24798. 2011
    ..We show that pre-therapy mutations in gag cleavage site sequence were significantly associated with the virological outcome of a first-line LPV/r single drug regimen in the Monark trial...
  45. ncbi Impact of 5 years of maximally successful highly active antiretroviral therapy on CD4 cell count and HIV-1 DNA level
    Jean Paul Viard
    Service d immunologie clinique, Universite Rene Descartes, Faculte de Medecine Necker Enfants Malades, Paris, France
    AIDS 18:45-9. 2004
    ..e., constant plasma HIV-1 RNA load suppression...
  46. ncbi Two-year outcomes of children on non-nucleoside reverse transcriptase inhibitor and protease inhibitor regimens in a South African pediatric antiretroviral program
    Heather B Jaspan
    School of Child and Adolescent Health, University of Cape Town, South Africa
    Pediatr Infect Dis J 27:993-8. 2008
    ..Few data exist on the efficacy of the limited regimens for children with HIV, which are available in sub-Saharan Africa...
  47. pmc Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial
    Judith Currier
    University of California, Los Angeles, CA, USA
    Ann Intern Med 153:349-57. 2010
    ..Women account for an increasing proportion of patients with HIV-1 but remain underrepresented in antiretroviral clinical trials...
  48. ncbi HIV-1 protease: mechanism and drug discovery
    Ashraf Brik
    Department of Chemistry, Skaggs Institute for Chemical Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Org Biomol Chem 1:5-14. 2003
  49. ncbi Sex differences in adverse reactions to antiretroviral drugs
    Ighovwerha Ofotokun
    Division of Infectious Diseases, Department of Internal Medicine, University of Kentucky Chandler Medical Center, Lexington, KY 40536, USA
    Top HIV Med 11:55-9. 2003
    ..These differences warrant further study...
  50. ncbi HIV protease inhibitors block Akt signaling and radiosensitize tumor cells both in vitro and in vivo
    Anjali K Gupta
    Department of Radiation and Biostatistics, University of Pennsylvania, Philadelphia 19104, USA
    Cancer Res 65:8256-65. 2005
    ..Insulin resistance and diabetes are recognized side effects of HIV protease inhibitors (HPIs), suggesting that these agents may inhibit Akt signaling...
  51. ncbi HIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy
    S G Deeks
    University of California, San Francisco and San Francisco General Hospital, 94110, USA
    AIDS 13:F35-43. 1999
    ..To determine the HIV RNA and CD4 cell response to both initial and salvage therapy with protease inhibitor-based therapy, and to examine the relationship between the virological response and pre-therapy characteristics...
  52. ncbi The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients
    J J Kiser
    School of Pharmacy, University of Colorado at Denver and Health Sciences Center, Denver, Colorado, USA
    Clin Pharmacol Ther 83:265-72. 2008
    ..Future studies should clarify the exact mechanism and whether there is an increased risk of nephrotoxicity...
  53. pmc A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs
    K Hertogs
    VIRCO, Central Virological Laboratory, Edegem, Belgium
    Antimicrob Agents Chemother 42:269-76. 1998
    ..This assay system facilitates the rapid large-scale phenotypic resistance determinations for all RT and PR inhibitors in one standardized assay...
  54. pmc Simplification strategies to reduce antiretroviral drug exposure: progress and prospects
    John E McKinnon
    Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Antivir Ther 14:1-12. 2009
    ..This article reviews progress in the simplification of antiretroviral therapy, recent clinical trial results and prospects for the future...
  55. pmc HIV aspartyl peptidase inhibitors interfere with cellular proliferation, ultrastructure and macrophage infection of Leishmania amazonensis
    Lívia O Santos
    Laboratório de Biologia Molecular e Doenças Endêmicas, Instituto Oswaldo Cruz IOC, Fundação Oswaldo Cruz FIOCRUZ, Rio de Janeiro, RJ, Brazil
    PLoS ONE 4:e4918. 2009
    ..Compounding these problems is the increase in the number of cases of Leishmania-HIV coinfection, due to the overlap between the AIDS epidemic and leishmaniasis...
  56. ncbi HIV-1 protease inhibitor induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2
    Takayuki Ikezoe
    Department of Internal Medicine, Kochi Medical School, Nankoku, Kochi, Japan
    Mol Cancer Ther 3:473-9. 2004
    ..Taken together, protease inhibitors might be useful for treatment of individuals with MM...
  57. ncbi Human lipodystrophies linked to mutations in A-type lamins and to HIV protease inhibitor therapy are both associated with prelamin A accumulation, oxidative stress and premature cellular senescence
    M Caron
    INSERM U680, Universite Pierre et Marie Curie Paris 6, Faculte de Medecine, site Saint Antoine, 27 rue Chaligny, 75571 Paris Cedex 12, France
    Cell Death Differ 14:1759-67. 2007
    ..These alterations could participate in the pathophysiology of lipodystrophic syndromes and lead to premature ageing complications...
  58. ncbi Urolithiasis in HIV-positive patients treated with atazanavir
    Carine Couzigou
    Service des Maladies Infectieuses et Tropicales, AP HP, Hopital Paul Brousse, Villejuif, France
    Clin Infect Dis 45:e105-8. 2007
    ..Patients with low water intake, high urinary pH, and a prior history of urinary stones may have a higher risk of atazanavir-associated urine crystallization...
  59. ncbi Fifteen years of HIV Protease Inhibitors: raising the barrier to resistance
    Annemarie M J Wensing
    Dept of Virology, University Medical Center Utrecht, Utrecht, The Netherlands
    Antiviral Res 85:59-74. 2010
    ..Detailed knowledge of the structure of HIV protease and its substrate has led to the design of specific HIV protease inhibitors. Unfortunately, resistance to all protease inhibitors (PIs) has been observed and the genetic basis of ..
  60. pmc Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis
    Julie B Dumond
    School of Pharmacy, University of North Carolina at Chapel Hill, North Carolina, USA
    AIDS 21:1899-907. 2007
    ..To describe first dose and steady state antiretroviral drug exposure in the female genital tract...
  61. ncbi Endoplasmic reticulum stress links dyslipidemia to inhibition of proteasome activity and glucose transport by HIV protease inhibitors
    Rex A Parker
    Metabolic and Cardiovascular Discovery Biology, Bristol Myers Squibb Pharmaceutical Research Institute, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    Mol Pharmacol 67:1909-19. 2005
    ....
  62. pmc HIV therapy, metabolic syndrome, and cardiovascular risk
    Vivian Pao
    Department of Veterans Affairs Medical Center, Metabolism Section Box 111F, 4150 Clement Street, San Francisco, CA 94121, USA
    Curr Atheroscler Rep 10:61-70. 2008
    ..It remains to be determined whether CVD rates in HIV infection are higher than might be predicted from traditional risk factors, including smoking...
  63. ncbi Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection
    K Mulligan
    Department of Medicine, University of California, San Francisco General Hospital, 94110, USA
    J Acquir Immune Defic Syndr 23:35-43. 2000
    ..However, at the moment, the risks associated with these metabolic effects do not appear to outweigh improvements in survival seen with PI therapy...
  64. ncbi Up-regulation of P-glycoprotein by HIV protease inhibitors in a human brain microvessel endothelial cell line
    Jason A Zastre
    Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada
    J Neurosci Res 87:1023-36. 2009
    ..Long-term exposure of atazanavir or ritonavir to brain microvessel endothelium may result in further limitations in brain drug permeability as a result of the up-regulation of P-gp expression and function...
  65. ncbi Evaluation of antitumoral properties of the protease inhibitor indinavir in a murine model of hepatocarcinoma
    Vincenzo Esposito
    Third Division Cotugno Hospital, Naples, Italy
    Clin Cancer Res 12:2634-9. 2006
    ..We aimed to evaluate the antineoplastic potential activities of the protease inhibitor indinavir (Crixivan) in in vitro and in vivo hepatocarcinoma models...
  66. pmc Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages
    Weibin Zha
    Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Virginia, United States of America
    PLoS ONE 8:e54349. 2013
    ..However, the underlying mechanisms of HIV PI-induced BBR accumulation are unknown. This study examined the role of P-glycoprotein (P-gp) in HIV PI-mediated accumulation of BBR in macrophages...
  67. ncbi Initial highly-active antiretroviral therapy with a protease inhibitor versus a non-nucleoside reverse transcriptase inhibitor: discrepancies between direct and indirect meta-analyses
    Roger Chou
    Oregon Evidence Based Practice Center, Oregon Health and Science University, Portland, OR 97239, USA
    Lancet 368:1503-15. 2006
    ..However, direct evidence for competing interventions is deemed more reliable than indirect evidence for making treatment decisions. We did a meta-analysis of head-to-head trials and compared the results with those of indirect analyses...
  68. pmc Atazanavir pharmacokinetics with and without tenofovir during pregnancy
    Mark Mirochnick
    Department of Pediatrics, Boston University School of Medicine, Boston, MA, USA
    J Acquir Immune Defic Syndr 56:412-9. 2011
    ..Few data are available describing atazanavir exposure during pregnancy, especially when used in combination with tenofovir, whose coadministration with atazanavir results in decreased atazanavir exposure...
  69. pmc Pharmacokinetic interaction study of ritonavir-boosted saquinavir in combination with rifabutin in healthy subjects
    Xiaoping Zhang
    Department of Clinical Pharmacology, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
    Antimicrob Agents Chemother 55:680-7. 2011
    ..The AUC(0-96) of rifabutin was not affected, and C(max) increased by 68%. Monitoring of neutropenia and liver enzyme levels is recommended for patients receiving rifabutin with saquinavir-ritonavir BID...
  70. ncbi P-Glycoprotein and transporter MRP1 reduce HIV protease inhibitor uptake in CD4 cells: potential for accelerated viral drug resistance?
    K Jones
    Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK
    AIDS 15:1353-8. 2001
    ..HIV-1 protease inhibitors interact with both; consequently the transporters could reduce the local concentration of HIV-1 protease inhibitors and, thus, influence the selection of viral mutants...
  71. pmc The human immunodeficiency virus protease inhibitor ritonavir inhibits lung cancer cells, in part, by inhibition of survivin
    Anjaiah Srirangam
    Division of Hematology, Oncology and Transplantation, University of Minnesota and University of Minnesota Cancer Center, Minneapolis, MN 55455, USA
    J Thorac Oncol 6:661-70. 2011
    ..Ritonavir is a potential therapeutic agent in lung cancer, but its targets in lung adenocarcinoma are unknown, as are candidate biomarkers for its activity...
  72. pmc Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease
    Thomas P Young
    Abbott Molecular, 1300 East Touhy Avenue, Des Plaines, IL 60018 3315, USA
    Antimicrob Agents Chemother 54:4903-6. 2010
    ..L76V was associated with a 2- to 6-fold decrease in susceptibility to lopinavir, darunavir, amprenavir, and indinavir and a 7- to 8-fold increase in susceptibility to atazanavir and saquinavir...
  73. ncbi Multiple effects of amprenavir against Candida albicans
    Lys A Braga-Silva
    Laboratorio de Estudos Integrados em Bioquimica Microbiana, Departamento de Microbiologia Geral, Centro de Ciencias da Saude, Instituto de Microbiologia Prof Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
    FEMS Yeast Res 10:221-4. 2010
    ..albicans and also promoted ultrastructural alterations. Esterase activity, sterol content, biofilm formation and the expression of surface mannose- and sialic acid-rich glycoconjugates were also reduced by amprenavir...
  74. ncbi SOLO: 48-week efficacy and safety comparison of once-daily fosamprenavir /ritonavir versus twice-daily nelfinavir in naive HIV-1-infected patients
    Joseph C Gathe
    Therapeutic Concepts, P A, Houston, Texas, USA
    AIDS 18:1529-37. 2004
    ..To compare the magnitude and durability of the antiviral response to fosamprenavir (FPV) plus ritonavir (RTV) once-daily (FPV/r QD) with nelfinavir twice-daily (NFV BID), each administered with abacavir and lamivudine twice-daily...
  75. ncbi Identification of the minimal conserved structure of HIV-1 protease in the presence and absence of drug pressure
    Francesca Ceccherini-Silberstein
    Department of Experimental Medicine, University of Rome Tor Vergata, Italy
    AIDS 18:F11-9. 2004
    ..To define the extent of amino acid protease (PR) conservation in vivo in the absence and presence of pharmacological pressure in a large patient cohort...
  76. ncbi Energetic basis for drug resistance of HIV-1 protease mutants against amprenavir
    Parimal Kar
    Department of Theory and Bio Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany
    J Comput Aided Mol Des 26:215-32. 2012
    ..Detailed understanding of the molecular forces governing binding and drug resistance might assist in the design of new inhibitors against HIV-1 PR variants that are resistant against current drugs...
  77. ncbi Efficacy and safety outcomes among treatment-experienced women and men treated with etravirine in gender, race and clinical experience
    Sally Hodder
    Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark, NJ 07101, USA
    AIDS Res Hum Retroviruses 28:544-51. 2012
    ..ETR is effective and well tolerated in treatment-experienced patients with HIV-1, with similar outcomes among women and men...
  78. ncbi Examination of noninferiority, safety, and tolerability of lopinavir/ritonavir and raltegravir compared with lopinavir/ritonavir and tenofovir/ emtricitabine in antiretroviral-naïve subjects: the progress study, 48-week results
    Jacques Reynes
    Department of Infectious and Tropical Diseases, Montpellier University Hospital, Montpellier, France
    HIV Clin Trials 12:255-67. 2011
    ..The purpose of this study is to evaluate whether a new NRTI-sparing regimen may provide an alternative for persons for whom traditional regimens may not be the best option...
  79. pmc A multifaceted analysis of HIV-1 protease multidrug resistance phenotypes
    Kathleen M Doherty
    Department of Chemistry, Wellesley College, MA 02481, USA
    BMC Bioinformatics 12:477. 2011
    ..Understanding the phenotypic and genotypic patterns responsible for multi-PI resistance is necessary for developing PIs that are active against clinically-relevant PI-resistant HIV-1 variants...
  80. ncbi Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine
    Dale J Kempf
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois, USA
    J Infect Dis 189:51-60. 2004
    ..These differences suggest substantially different genetic and pharmacological barriers to resistance for these 2 protease inhibitors and may have implications for strategies for initiating antiretroviral therapy...
  81. ncbi Ritonavir inhibits the two main prasugrel bioactivation pathways in vitro: a potential drug-drug interaction in HIV patients
    Youssef Daali
    Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland
    Metabolism 60:1584-9. 2011
    ..This finding suggests a potential significant drug-drug interaction between these two drugs...
  82. ncbi An increase in viral replicative capacity drives the evolution of protease inhibitor-resistant human immunodeficiency virus type 1 in the absence of drugs
    Noortje M van Maarseveen
    Department of Virology, Eijkman Winkler Center, University Medical Center Utrecht, Utrecht, The Netherlands
    J Acquir Immune Defic Syndr 42:162-8. 2006
    ..In the case of these viruses, it is not so likely that higher fitness peaks are present within the sequence space, and therefore, these variants will persist in the absence of drug pressure...
  83. ncbi Lopinavir
    M Hurst
    Adis International Limited, Mairangi Bay, Auckland, New Zealand
    Drugs 60:1371-9; discussion 1380-1. 2000
    ..Diarrhoea, nausea and asthenia were the most frequently reported adverse effects in patients receiving lopinavir/ritonavir-based regimens. Elevated total cholesterol, triglyceride and hepatic enzyme levels were also reported...
  84. ncbi Antiretrovirals as antimalarial agents
    Tina S Skinner-Adams
    Malaria Biology Laboratory, Australian Centre for International and Tropical Health and Nutrition, Queensland Institute of Medical Research and School of Population Health, University of Queensland, St Lucia, Queensland, Australia
    J Infect Dis 190:1998-2000. 2004
    ..These findings are particularly important in light of both the high rate of malaria and HIV-1 coinfection in sub-Saharan Africa and the effort to employ highly active antiretroviral therapy in these regions...
  85. ncbi Effect of an antiretroviral regimen containing ritonavir boosted lopinavir on intestinal and hepatic CYP3A, CYP2D6 and P-glycoprotein in HIV-infected patients
    C Wyen
    Department of Internal Medicine, Hospital of the University of Cologne, Koln, Germany
    Clin Pharmacol Ther 84:75-82. 2008
    ..In conclusion, CYP3A, CYP2D6, and P-glycoprotein are profoundly inhibited in patients receiving ritonavir boosted lopinavir. The covariates investigated are not useful for a priori dose selection...
  86. ncbi Relationship between plasma protease inhibitor concentrations and lipid elevations in HIV patients on a double-boosted protease inhibitor regimen (saquinavir/lopinavir/ritonavir)
    Martin S Rhee
    Tufts Medical Center, Division of Geographic Medicine and Infectious Disease, 800 Washington St, Box 41, Boston, MA 02111, USA
    J Clin Pharmacol 50:392-400. 2010
    ..Factors other than systemic exposure to PIs (such as host or genetic factors) may modulate the hyperlipidemic effect of PIs...
  87. pmc Predicting tipranavir and darunavir resistance using genotypic, phenotypic, and virtual phenotypic resistance patterns: an independent cohort analysis of clinical isolates highly resistant to all other protease inhibitors
    Annie Talbot
    Clinique du Quartier Latin and Centre Hospitalier de l Université de Montréal, Montreal, Quebec, Canada
    Antimicrob Agents Chemother 54:2473-9. 2010
    ..Generally, GISs predict susceptibility to darunavir substantially better than they predict susceptibility to tipranavir...
  88. ncbi Simultaneous determination of five HIV protease inhibitors nelfinavir, indinavir, ritonavir, saquinavir and amprenavir in human plasma by LC/MS/MS
    Jingduan Chi
    Department of Clinical Pharmacy, Drug Research Unit, School of Pharmacy, University of California, San Francisco, CA 94143, USA
    J Pharm Biomed Anal 30:675-84. 2002
    ..tandem mass spectrometry (LC-MS-MS) method has been developed to measure the levels of five HIV protease inhibitors nelfinavir (NFV), indinavir (IDV), ritonavir (RTV), saquinavir (SQV) and amprenavir (APV) in human plasma...
  89. ncbi High incidence of adverse events in healthy volunteers receiving rifampicin and adjusted doses of lopinavir/ritonavir tablets
    Hanneke M J Nijland
    Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, The Netherlands
    AIDS 22:931-5. 2008
    ..Our objective was to study the combined use of rifampicin and the newly introduced lopinavir/ritonavir tablets...
  90. ncbi Lopinavir co-induces insulin resistance and ER stress in human adipocytes
    Mansour Djedaini
    Institute of Biology Development and Cancer, University of Nice Sophia Antipolis, CNRS, 28 Avenue de Valombrose, 06107 Nice cedex2, France
    Biochem Biophys Res Commun 386:96-100. 2009
    ..Thus, this protein represents a promising therapeutic target for development of new PIs devoid of adverse metabolic effects...
  91. ncbi HIV envelope gp120-mediated regulation of osteoclastogenesis via receptor activator of nuclear factor kappa B ligand (RANKL) secretion and its modulation by certain HIV protease inhibitors through interferon-gamma/RANKL cross-talk
    J Mohamad Fakruddin
    Laboratory for AIDS Virus Research, Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Biol Chem 278:48251-8. 2003
    ..They also suggest a novel therapeutic approach to HIV osteopenia through modulation of these two molecules...
  92. ncbi Positioning of HIV-protease inhibitors in clinical practice
    M Andreoni
    Department of Public Health and Cell Biology, School of Medicine, University of Rome Tor Vergata, Rome, Italy
    Eur Rev Med Pharmacol Sci 16:10-8. 2012
    ....
  93. ncbi Double-boosted protease inhibitor antiretroviral regimens: what role?
    Esteban Ribera
    Infectious Diseases Department, Hospital Universitari Vall d Hebron, Barcelona, Spain
    Drugs 68:2257-67. 2008
    ..The fixed combination of lopinavir/ritonavir tablets makes it easier to boost with another PI at the same time, without requiring ritonavir refrigeration, and this may be particularly useful in this setting...
  94. pmc Modulation of HIV-1 Gag NC/p1 cleavage efficiency affects protease inhibitor resistance and viral replicative capacity
    Noortje M van Maarseveen
    Dept of Medical Microbiology, Virology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
    Retrovirology 9:29. 2012
    ....
  95. ncbi Ritonavir greatly impairs CYP3A activity in HIV infection with chronic viral hepatitis
    Tamsin A Knox
    Nutrition Infection Division, Department of Public Health and Family Medicine, Tufts University School of Medicine, Boston, MA 02111, USA
    J Acquir Immune Defic Syndr 49:358-68. 2008
    ..Ritonavir is a powerful inhibitor of cytochrome P450 3A (CYP3A) that metabolizes many antiretrovirals. We examined the effect of ritonavir and of chronic viral hepatitis (CVH) status on CYP3A activity...
  96. pmc HIV protease inhibitors alter innate immune response signaling to double-stranded RNA in oral epithelial cells: implications for immune reconstitution inflammatory syndrome?
    Robert J Danaher
    Department of Oral Health Practice, University of Kentucky Medical Center, Lexington, Kentucky, USA
    AIDS 24:2587-90. 2010
    In this investigation, several HIV protease inhibitors altered the virally associated, double-stranded RNA (dsRNA)-stimulated, innate immune response...
  97. pmc Bilirubin-a potential marker of drug exposure in atazanavir-based antiretroviral therapy
    Dinko Rekic
    Unit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology, Sahlgrenska Academy at University of Gothenburg, Sweden
    AAPS J 13:598-605. 2011
    ..6 to 8.1 h. A nomogram, which can be used to indicate suboptimal atazanavir exposure and non-adherence, was constructed based on model simulations...
  98. pmc Human immunodeficiency virus type 1 protease-correlated cleavage site mutations enhance inhibitor resistance
    Madhavi Kolli
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA
    J Virol 83:11027-42. 2009
    ..Thus, cleavage site mutations should be considered when assessing the level of PI resistance...
  99. pmc Berberine inhibits HIV protease inhibitor-induced inflammatory response by modulating ER stress signaling pathways in murine macrophages
    Weibin Zha
    Department of Microbiology and Immunology and Internal Medicine Gastroenterology and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, Virginia, United States of America
    PLoS ONE 5:e9069. 2010
    ..This study examined the effect of berberine, a traditional herb medicine, on HIV PI-induced inflammatory response and further investigated the underlying cellular/molecular mechanisms in macrophages...
  100. ncbi Role of Baseline pol Genotype in HIV-1 Fitness Evolution
    Jan Weber
    Department of Virology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Acquir Immune Defic Syndr 33:448-60. 2003
    ..65, P < 0.0001). However, our results suggest that the preexistence of secondary mutations in protease genetic background may have implications in HIV-1 fitness evolution and virologic response to antiretroviral therapy...
  101. pmc Full-length HIV-1 Gag determines protease inhibitor susceptibility within in vitro assays
    Ravindra K Gupta
    MRC Centre for Medical Molecular Virology, University College London, Windeyer Institute, London, UK
    AIDS 24:1651-5. 2010
    ..We wished to assess the contribution of full-length Gag to protease inhibitor susceptibility in viruses unexposed to protease inhibitors, in particular from the most common HIV-1 subtypes, namely subtype A and C...

Research Grants64

  1. Drug Interactions at the Human Blood-Brain Barrier
    Jashvant D Unadkat; Fiscal Year: 2010
    ..g. anti-HIV protease inhibitors)...
  2. Effect of HIV protease inhibitor on alcohol induced ER stress and liver injury.
    Cheng Ji; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): HIV protease inhibitors (HIV PIs) are used in the highly ctive antiretroviral therapy (HAART). However, HIV PIs are often associated with development of liver damages...
  3. Designing HIV Protease Inhibitors with Lower Dosing Requirements and Lower Toxici
    Mitchell W Mutz; Fiscal Year: 2013
    ..b>HIV protease inhibitors are a mainstay of highly active antiretroviral therapy (HAART) with annual sales of over $2.5 billion...
  4. Mechanisms of HIV Protease Inhibitor-Induced Lipid Dysregulation in Adipocytes
    BETH S ZHA; Fiscal Year: 2012
    ..insulin resistance, and lipodystrophy observed in patients receiving HAART have been linked to HIV protease inhibitors (PI)...
  5. Natural Product-Inspired Method for Enhancing HIV Protease Inhibitors
    Jason E Gestwicki; Fiscal Year: 2013
    ..to HAART-associated complications is the poor metabolic stability and low cellular penetration of the HIV protease inhibitors. Our group has been exploring a new method for addressing these limitations...
  6. DIRECT EFFECTS OF ANTIRETROVIRAL THERAPY ON CARDIAC ENERGY HOMEOSTASIS
    Paul W Hruz; Fiscal Year: 2013
    ..The studies in this proposal are intended to establish direct effects of HIV protease inhibitors (PIs) on heart function in the setting of concomitant myocardial stress or injury, to identify the ..
  7. Epigenetic Regulation of HSV Infection of Oral Cells
    David M Knipe; Fiscal Year: 2013
    ..HIV+/anti-retroviral treated individuals versus HIV- individuals and in oral epithelial cells treatd with HIV protease inhibitors, and define the epigenetic mechanisms operative in oral tumor cells. 3...
  8. Nelfinavir in SLE: A Pilot Phase IIa Clinical Trial
    Betty Diamond; Fiscal Year: 2013
    ..The successful completion of this proof-of-concept study will lay the groundwork for a definitive clinical trial. ..
  9. Garlic Metabolism and Cytochrome P450 Modulation
    Danny Shen; Fiscal Year: 2007
    ..supplements and several narrow therapeutic drugs, including anticoagulants (warfarin, fuindione) and HIV protease inhibitors (saquinavir, ritonavir), have been reported within the past 2 years...
  10. ANTIRETROVIRAL THERAPIES AND SUBSTANCE ABUSE
    David Greenblatt; Fiscal Year: 2002
    ..Highly active antiretroviral therapies (HAART), including the HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), constitute major advances in the ..
  11. Unnatural amino acids by deracemization
    PAUL PHILLIP TAYLOR; Fiscal Year: 2010
    ..These amino acids are in great demand for the synthesis of a wide range of important pharmaceutical compounds such HIV protease inhibitors, anti-cancer agents and anti-diabetic drugs.
  12. Impact of Alcohol on HIV Protease Inhibitor-induced ER Stress and Lipotoxicity
    HUIPING ROSE ZHOU; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The hepatic lipotoxicity specifically associated with HIV protease inhibitors (PIs), the core component of highly active anti-retroviral therapy (HAART), has become a major concern in the clinic, ..
  13. Drug-induced liver injury associated with anti-retroviral therapy
    Xiaochao Ma; Fiscal Year: 2012
    ..understanding of liver injury associated with ritonavir-containing protease inhibitor regimens, which will be applied toward the development of an evidence-based approach to improve the safety profile of HIV protease inhibitors.
  14. PROTEASE INHIBITOR-INDUCED HYPERLIPIDEMIA IN AIDS
    Virgil Brown; Fiscal Year: 2004
    ..These are specific agents that are effective in reducing triglyceride as well as improving insulin resistance. ..
  15. Multilevel Parallelization of Software for Accurate Protein-Ligand Affinities
    Simon Webb; Fiscal Year: 2013
    ..For example, the HIV protease inhibitors are important AIDS treatments that work by binding in the active site of the protease enzyme and ..
  16. HIV PROTEASE INHIBITORS EFFECT--NENDOTHELIAL DYSFUNCTION
    Changyi Chen; Fiscal Year: 2004
    DESCRIPTION (Adapted from the applicant's abstract) 1). To define the role of HIV protease inhibitors in endothelium-dependent vasorelaxation and endothelial morphology...
  17. Alcohol and HIV protease inhibitors interactions
    Dennis Feierman; Fiscal Year: 2003
    ..S.A.I: To characterize the pharmacokinetics of orally administered HIV protease inhibitors in rats fed the Leiber-DeCarli ethanol-containing diet, and pair fed and ad-lib controls...
  18. Antiadipogenic Influence of HIV Protease Inhibitors
    M Lane; Fiscal Year: 2005
    ..is to elucidate the molecular basis of the lipodystrophy syndrome (LDS) in HIV+ patients treated with HIV protease inhibitors (PIs)...
  19. IMPROVING BIOAVAILABILITY OF RGD PEPTIDOMIMETICS
    Teruna Siahaan; Fiscal Year: 2000
    ..The biological activity of the cyclic prodrugs of RGD-peptidomimetics and their respective parent compounds will be evaluated. ..
  20. HIV PROTEASE INHIBITORS AND ATHEROSCLEROSIS
    Eric Smart; Fiscal Year: 2006
    DESCRIPTION: (provided by applicant) We hypothesize that HIV protease inhibitors alter macrophage class B scavenger receptor-dependent uptake and efflux of cholesterol thereby promoting the formation of lipid-laden macrophages and ..
  21. Effects of HIV Protease Inhibitors of Endothelial Barrie
    Changyi Chen; Fiscal Year: 2005
    The HIV protease inhibitors as a part of highly active antiretroviral therapy (HAART) have improved the course of HIV disease...
  22. Ceramide, Membrane Glycolipids and Glycoprotein Expression
    Myles C Cabot; Fiscal Year: 2010
    ..This enhancement would dull cellular responses to antibiotics, antitumor agents, and HIV protease inhibitors. The aims of this proposal are: 1. to determine the influence of GCS on MDR1/P-gp expression;2...
  23. HIV PROTEASE INHIBITOR & LIPOPROTEIN RECEPTOR IMPAIRMENT
    Dudley Strickland; Fiscal Year: 2004
    ..In vitro cell culture experiments and animal models will be used to test the hypothesis that HIV protease inhibitors interfere with normal function of certain low density lipoprotein receptor family members, and that ..
  24. EFFECT OF HIV PROTEASE INHIBITORS ON ENDOTHELIAL DYSFUNC
    Harold McClure; Fiscal Year: 2004
    DESCRIPTION (Adapted from the applicant's abstract) To define the role of HIV protease inhibitors in endothelium-dependent vasorelaxation and endothelial morphology...
  25. HAART Regimens in Substance Abusers
    David Greenblatt; Fiscal Year: 2003
    DESCRIPTION: The availability of highly active antiretroviral therapies (HAART), including the HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), has prolonged survival and improved quality of ..
  26. Human CD4+ T Cell Based HighThroughput Assay-Drug-R(RMI)
    Chen Chen Kan; Fiscal Year: 2005
    ..morbidity/mortality as well as disease progress of AIDS, were successfully controlled by clinical use of HIV protease inhibitors. However, current HIV protease inhibitors, from the first generation drug indinavir to the most recent ..
  27. Commercial Preparation of Unnatural Amino Acids by Deracemization
    Paul Taylor; Fiscal Year: 2007
    ..These amino acids are in great demand for the synthesis of a wide range of important pharmaceutical compounds such HIV protease inhibitors, anti-cancer agents and anti-diabetic drugs. [unreadable] [unreadable] [unreadable]
  28. ORAL BIOAVAILABILITY AND VARIABILITY OF ANTIAIDS DRUGS
    Patrick Sinko; Fiscal Year: 2000
    ..The specific drugs to be studied include HIV protease inhibitors (saquinavir, ritonavir), non-nucleoside reverse transcriptase inhibitors (delaviridine, UC-781), and ..
  29. HIV protease inhibitors, marcophage function/estrogen
    Melinda Wilson; Fiscal Year: 2007
    ..We will use the human monocyte/macrophage cell line, THP-1 to define the effects 17??estradiol on the HIV protease inhibitors ritonavir and amprenavir induced alterations of CD36 expression and CD36-dependent function by measuring ..
  30. Bone Loss and Its Prevention in HIV Patients
    F Ross; Fiscal Year: 2006
    DESCRIPTION (Provided by the applicant): The use of HIV protease inhibitors (PIS), combined with other anti-retroviral agents, is central to dramatic decline in the morbidity and mortality of HIV infection...
  31. TRANSPORT CHARACTERISTICS OF PEPTIDE MIMETICS
    RONALD BORCHARDT; Fiscal Year: 2003
    ..g., HIV protease inhibitors, glycoprotein (gp) IIb/IIIa receptor antagonists) with novel therapeutic indications (e.g...
  32. FPIA FOR SAQUINAVIR AND RITONAVIR HIV INHIBITORS
    Charles Harrington; Fiscal Year: 2000
    ..PROPOSED COMMERCIAL APPLICATION: Measurement of HIV Protease Inhibitors will become a standard of treatment in the application of these drugs in my...
  33. Improved Anti-HIV Therapy with P-glycoprotein Inhibitors
    KEVIN FRENCH; Fiscal Year: 2002
    Current treatment protocols for AIDS involve combinations of nucleoside analogs and HIV protease inhibitors, but are not successful in curing the disease...
  34. PROTEASE INHIBITORS INDUCE AN ATHEROGENIC LIPOPROTEIN
    Gary Simon; Fiscal Year: 2004
    ..In vitro cell culture experiments and animal models will be used to test the hypothesis that HIV protease inhibitors interfere with normal function of certain low density lipoprotein receptor family members, and that ..
  35. TARGETED CHEMOTHERAPY TO HIV INFECTED MACROPHAGES
    FRANCIS SZOKA; Fiscal Year: 1991
    ..The compounds to be tested include reverse transcriptase inhibitors, anti-HIV sense oligonucleotides and HIV protease inhibitors. Novel pH sensitive liposome combinations will be used to deliver the high molecular weight compounds ..
  36. HIV Protease Inhibitors & Glucose Transport
    Mike Mueckler; Fiscal Year: 2007
    ..unreadable] 2) To test the hypothesis that PI-mediated inhibition of glucose transport directly contributes to lipodystrophy by suppressing adipogenesis and/or by enhancing adipocyte apoptosis. [unreadable] [unreadable] [unreadable]..
  37. Design of enzyme-based therapeutic drug monitoring kit
    Sergei Gulnik; Fiscal Year: 2003
    ..we have designed a novel, enzyme-based assay (ENZ-PK) for measuring the total inhibitor concentration of HIV protease inhibitors (HIV PIs) in human blood samples...
  38. MDR1 and Related Proteins during HIV PI Exposure
    David Greenblatt; Fiscal Year: 2005
    ..The HIV protease inhibitors (PIs) interact with P-gp, but the results from diverse experimental paradigms are often conflicting...
  39. FPIA FOR INDINAVIR AND NELFINAVIR HIV INHIBITORS
    Charles Harrington; Fiscal Year: 1999
    ..PROPOSED COMMERCIAL APPLICATION: Measurement for HIV Protease Inhibitors will become a standard of treatment in the application of these drugs in HIV...
  40. GENDER EFFECTS ON HIV BIOLOGY
    Warner Greene; Fiscal Year: 2006
    ..This project will also assess how changes in these proteins may affect the response to HIV protease inhibitors that are all substrates for both proteins. Core A, led by Ruth Greenblatt...
  41. TARGET SPECIFICITY FOR HIV PROTEASE INHIBITORS
    Xinli Lin; Fiscal Year: 2001
    ..However, the inhibition of the HIV protease inhibitors toward new human aspartic proteases, which were not discovered during the development of the current ..
  42. A NEW SOFTWARE FOR FINE SLICE DATA COLLECTION
    RONALD HAMLIN; Fiscal Year: 2002
    ..New HIV protease inhibitors which now can control AIDs disease in most patients are the testimonies of the success of this drug ..
  43. Measurements of HIV protease inhibitors in patient sera
    ZHIBO GAN; Fiscal Year: 2001
    ..Experiments are designed to obtain preliminary data for the development of a practical and robust test comparable in accuracy with those obtained by HPLC methodology. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE ..
  44. ADHERENCE TO HAART AMONG INCARCERATED SUBSTANCE USERS
    Andrew Kaplan; Fiscal Year: 2003
    ..In the North Carolina Department of Corrections, all inmates on HAART receive HIV protease inhibitors by DOT...
  45. FAT REDISTRIBUTION AND METABOLIC CHANGE IN HIV INFECTION
    Carl Grunfeld; Fiscal Year: 2006
    ..to changes in fat distribution and lipid and glucose metabolism that appeared with the introduction of HIV protease inhibitors (PI). However, there is controversy over the role of PI...
  46. INHIBITORS OF RETROVIRAL PROTEASE
    GARLAND MARSHALL; Fiscal Year: 1993
    ..This proposal aims at the development of specific HIV protease inhibitors capable of preventing viral replication with the hope that these compounds may prove therapeutically ..
  47. DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS
    Arun K Ghosh; Fiscal Year: 2010
    ..This research integrates organic synthesis, protein-ligand x-ray crystallography, molecular modeling and in-depth virus and cell-biological studies to design the next generation of HIV-1 protease inhibitors. ..
  48. Measurement of HIV protease inhibitors in patient sera
    ZHIBO GAN; Fiscal Year: 2003
    During phase I the feasibility of a test kit for the fluorometric measurement of HIV protease inhibitors (PI) in human serum has been demonstrated...
  49. DEVELOPMENT OF LIGAND ASSISTED ASYMMETRIC SYNTHESES
    Arun Ghosh; Fiscal Year: 2001
    ..Besides the broad range of scope and generality, this line of research will provide excellent opportunities to teach and train graduate and undergraduate students in the laboratory. ..
  50. Statistical Methods for Adherence and HIV Outcomes
    Honghu Liu; Fiscal Year: 2006
    ..such as dose-interval, which is particularly important for medications with a short half-life such as HIV protease inhibitors. No single adherence measure currently in use integrates the different aspects of adherence behavior...
  51. 400 MHZ NUCLEAR MAGNETIC RESONANCE SPECTROMETER
    David Vander Velde; Fiscal Year: 2001
    ..These methods have potential applications in peptidomimetics that can be used as antihypertensive agents, HIV protease inhibitors, and delivery of anticancer agents...
  52. NEW SOFTWARE FOR FINE SLICE DATA COLLECTION
    RONALD HAMLIN; Fiscal Year: 1999
    ..New HIV protease inhibitors which now can control AIDs disease in most patients are the testimonies of the success of this drug ..
  53. Treatment Intensification for Drug-Resistant HIV
    Steven Deeks; Fiscal Year: 2004
    ..Funding for the pilot clinical trial has been obtained from other sources; funding is requested in this proposal only for costs associated with the measurements of immunologic response to drug-resistant HIV-1. ..
  54. The impact of early antiretroviral therapy on HIV persistence and inflammation
    STEVEN GRANT DEEKS; Fiscal Year: 2010
    ..Our work may also provide important insights in the role of chronic inflammation in driving viral persistence, and hence may lead to the development of novel interventions. ..
  55. Immunologic Control of Drug-resistant HIV-1
    Steven Deeks; Fiscal Year: 2005
    ..Finally, since we will estimate the relative in vivo thresholds for HIV-mediated immunogenicity and pathogenicity, these studies may also have implications for vaccine development. ..
  56. HIV Protease Inhibitors and Hepatic Lipid Dysregulation
    Phillip Hylemon; Fiscal Year: 2008
    ..The mechanism(s) by which HIV protease inhibitors (PI) therapy leads to dysregulation of sterol and lipid metabolism is unclear...
  57. ANESTHETIC RENAL METABOLISM--MECHANISMS AND CONSEQUENCES
    Evan Kharasch; Fiscal Year: 2002
    ..More broadly, resulting biochemical and clinical insights will be applicable to the numerous other nephrotoxic haloalkenes that are ubiquitous environmental contaminants. ..
  58. Mechanisms for Altered Glucose Homeostasis During HAART
    Paul W Hruz; Fiscal Year: 2010
    ..The metabolic changes that occur in association with the use of HIV protease inhibitors (Pis) have significant potential for increasing cardiac- associated morbidity and mortality...
  59. Novel noninvasive assessment of cytochrome P450 activity
    Evan Kharasch; Fiscal Year: 2009
    ..This approach may identify inter-individual variability in drug disposition and response;permit more individualized dosing, and reduces the cost of drug interaction studies. ..
  60. Mechanism of GLUT4 Inhibition by HIV Protease Inhibitor
    Paul Hruz; Fiscal Year: 2005
    ..The recent discovery that HIV protease inhibitors are capable of selectively inhibiting GLUT4, the major insulin responsive glucose transporter, is the ..
  61. VANDERBILT ADULT AIDS CLINICAL TRIALS UNIT
    David Haas; Fiscal Year: 2006
    ..The proposed ACTU will not only enroll patients into ACTG clinical trials, but will provide the ACTG the ability to address important questions concerning AIDS treatment and pathogenesis. ..
  62. INTEGRATE/PHARMACOKINETIC/ANTIRETROVIRUS RESISTANCE TEST
    Edward Acosta; Fiscal Year: 2006
    ..abstract_text> ..
  63. CNS Viral Dynamics and Cellular Immunity During AIDS
    David Haas; Fiscal Year: 2009
    ..Characterizing these relationships will expand our knowledge regarding key events that lead to AIDS dementia, and may suggest novel approaches to other immunologic or viral-mediated diseases that affect the brain. ..
  64. TESTING REVERSE TRANSCRIPTASE FIDELITY AS A HIV TARGET
    Baek Kim; Fiscal Year: 2001
    ..Third, the investigator plans to measure the capability of HIV with mutant RT genes characterized from the previous aims to escape from the selective pressure of HIV protease inhibitors.