Michael D Miller

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. doi request reprint Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection
    David A Cooper
    National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney
    N Engl J Med 359:355-65. 2008
  2. pmc A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding a critical gp41 epitope
    Michael D Miller
    Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19486, USA
    Proc Natl Acad Sci U S A 102:14759-64. 2005
  3. ncbi request reprint HIV-1 reverse transcriptase plus-strand initiation exhibits preferential sensitivity to non-nucleoside reverse transcriptase inhibitors in vitro
    Jay A Grobler
    Department of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 282:8005-10. 2007
  4. ncbi request reprint Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody
    Micah A Luftig
    Istituto di Ricerche di Biologia Molecolare P Angeletti, Via Pontina Km 30, 600, I 00040 Pomezia Rome, Italy
    Nat Struct Mol Biol 13:740-7. 2006
  5. ncbi request reprint In vitro evaluation of the anti-HIV activity and metabolic interactions of tenofovir and emtricitabine
    Katyna Borroto-Esoda
    Department of Clinical Virology, Gilead Sciences, Inc, Foster City, CA, USA
    Antivir Ther 11:377-84. 2006
  6. ncbi request reprint HIV resistance to the fusion inhibitor enfuvirtide: mechanisms and clinical implications
    Michael D Miller
    Department of Biological Chemistry, Merck Research Laboratories, P O Box 4, WP16 101, West Point, PA 19486, USA
    Drug Resist Updat 7:89-95. 2004
  7. ncbi request reprint Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 3: SAR studies on the benzylpyrazole segment
    Min Shu
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 14:947-52. 2004
  8. pmc A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase
    Daria J Hazuda
    Department of Biological Chemistry, Merck Research Laboratories, P O Box 4, West Point, PA 19486, USA
    Proc Natl Acad Sci U S A 101:11233-8. 2004
  9. ncbi request reprint Syntheses and SAR studies of 4-(heteroarylpiperdin-1-yl-methyl)-pyrrolidin-1-yl-acetic acid antagonists of the human CCR5 chemokine receptor
    K Shankaran
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 14:3419-24. 2004
  10. pmc Distinct mutation pathways of non-subtype B HIV-1 during in vitro resistance selection with nonnucleoside reverse transcriptase inhibitors
    Ming Tain Lai
    Department of Antiviral Research, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA
    Antimicrob Agents Chemother 54:4812-24. 2010

Detail Information

Publications76

  1. doi request reprint Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection
    David A Cooper
    National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney
    N Engl J Med 359:355-65. 2008
    ....
  2. pmc A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding a critical gp41 epitope
    Michael D Miller
    Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19486, USA
    Proc Natl Acad Sci U S A 102:14759-64. 2005
    ..Our data provide a structural framework for the design of new immunogens and therapeutic antibodies with crossneutralizing potential...
  3. ncbi request reprint HIV-1 reverse transcriptase plus-strand initiation exhibits preferential sensitivity to non-nucleoside reverse transcriptase inhibitors in vitro
    Jay A Grobler
    Department of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 282:8005-10. 2007
    ..The data presented here suggest that specific inhibition of plus-strand initiation may be an important mechanism by which NNRTIs block HIV-1 replication...
  4. ncbi request reprint Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody
    Micah A Luftig
    Istituto di Ricerche di Biologia Molecolare P Angeletti, Via Pontina Km 30, 600, I 00040 Pomezia Rome, Italy
    Nat Struct Mol Biol 13:740-7. 2006
    ..Thus, our data validate the gp41 N-peptide trimer fusion intermediate as a target for neutralizing antibodies and provide a template for identification of more potent and broadly neutralizing molecules...
  5. ncbi request reprint In vitro evaluation of the anti-HIV activity and metabolic interactions of tenofovir and emtricitabine
    Katyna Borroto-Esoda
    Department of Clinical Virology, Gilead Sciences, Inc, Foster City, CA, USA
    Antivir Ther 11:377-84. 2006
    ..We evaluated this combination for anti-HIV activity and intracellular metabolic interactions in vitro...
  6. ncbi request reprint HIV resistance to the fusion inhibitor enfuvirtide: mechanisms and clinical implications
    Michael D Miller
    Department of Biological Chemistry, Merck Research Laboratories, P O Box 4, WP16 101, West Point, PA 19486, USA
    Drug Resist Updat 7:89-95. 2004
    ..Many aspects of the complexities observed in ENF resistance are likely to be relevant for other classes of HIV entry inhibitors currently in development...
  7. ncbi request reprint Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 3: SAR studies on the benzylpyrazole segment
    Min Shu
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 14:947-52. 2004
    ..They demonstrate improved antiviral activity while retaining good pharmacokinetic profile and selectivity...
  8. pmc A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase
    Daria J Hazuda
    Department of Biological Chemistry, Merck Research Laboratories, P O Box 4, West Point, PA 19486, USA
    Proc Natl Acad Sci U S A 101:11233-8. 2004
    ..These studies provide a structural basis and rationale for developing integrase inhibitors with the potential for unique and nonoverlapping resistance profiles...
  9. ncbi request reprint Syntheses and SAR studies of 4-(heteroarylpiperdin-1-yl-methyl)-pyrrolidin-1-yl-acetic acid antagonists of the human CCR5 chemokine receptor
    K Shankaran
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 14:3419-24. 2004
    ..The synthesis and SAR of pyrrolidineacetic acid derivatives as CCR5 antagonists displaying potent binding and antiviral properties in a HeLa cell-based HIV-1 infectivity assay are discussed...
  10. pmc Distinct mutation pathways of non-subtype B HIV-1 during in vitro resistance selection with nonnucleoside reverse transcriptase inhibitors
    Ming Tain Lai
    Department of Antiviral Research, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA
    Antimicrob Agents Chemother 54:4812-24. 2010
    ..Thus, the interactions between NNRTIs and the residues in the NNRTIBPs of different subtypes may not be identical, leading to distinct mutation pathways during resistance selection in cell culture...
  11. ncbi request reprint Dissecting the effects of DNA polymerase and ribonuclease H inhibitor combinations on HIV-1 reverse-transcriptase activities
    Cathryn A Shaw-Reid
    Department of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania 19486 0004, USA
    Biochemistry 44:1595-606. 2005
    ....
  12. ncbi request reprint Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 2: Discovery of potent, selective, and orally bioavailable compounds
    Dong Ming Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 14:941-5. 2004
    ..This allowed us to prepare compounds such as 24 and 25 for the first time. A novel Pd-mediated N-dealkylation of alpha-(pyrrolidin-1-yl)acetic acid was also uncovered...
  13. pmc Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41
    Donna L Montgomery
    Department of Biologics Research, Merck Research Laboratories, West Point, PA, USA
    MAbs 1:462-74. 2009
    ....
  14. doi request reprint Assessment of the susceptibility of mutant HIV-1 to antiviral agents
    Ying Jie Wang
    Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19486, USA
    J Virol Methods 165:230-7. 2010
    ....
  15. ncbi request reprint Syntheses and biological evaluation of 5-(piperidin-1-yl)-3-phenyl-pentylsulfones as CCR5 antagonists
    K Shankaran
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 14:3589-93. 2004
    ..Our medicinal chemistry efforts in this area have resulted in the identification of N-alkyl piperidine sulfones as CCR5 antagonists. These compounds display potent binding and show antiviral properties in HIV-1 spread cell-based assays...
  16. pmc Antiviral activity and in vitro mutation development pathways of MK-6186, a novel nonnucleoside reverse transcriptase inhibitor
    Meiqing Lu
    Department of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania, USA
    Antimicrob Agents Chemother 56:3324-35. 2012
    ..More importantly, mutant viruses selected by MK-6186 showed FCs of <10 against EFV or etravirine (ETR), and the mutant viruses containing mutations selected by EFV or ETR were sensitive to MK-6186 (FCs of <10)...
  17. pmc Antiviral activity of MK-4965, a novel nonnucleoside reverse transcriptase inhibitor
    Ming Tain Lai
    Department of Antiviral Research, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA
    Antimicrob Agents Chemother 53:2424-31. 2009
    ..Taken together, these in vitro data show that MK-4965 possesses the desired properties for further development as a new NNRTI for the treatment of HIV-1 infection...
  18. ncbi request reprint Progress towards the development of a HIV-1 gp41-directed vaccine
    Georgia B McGaughey
    Department of Molecular Systems, Merck Research Laboratories, P O Box 4, West Point, PA 19486, USA
    Curr HIV Res 2:193-204. 2004
    ..The implication of these findings with regard to structural and immunological considerations is discussed...
  19. doi request reprint 10-Hydroxy-7,8-dihydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-diones: potent, orally bioavailable HIV-1 integrase strand-transfer inhibitors with activity against integrase mutants
    Catherine M Wiscount
    Department of Medicinal Chemistry, WP14 3, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 18:4581-3. 2008
    ..v. t(1/2)=5.3 h, f=17%)...
  20. ncbi request reprint A potent and orally active HIV-1 integrase inhibitor
    Melissa S Egbertson
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 17:1392-8. 2007
    ..A 1,6-naphthyridine inhibitor of HIV-1 integrase has been discovered with excellent inhibitory activity in cells, good pharmacokinetics, and an excellent ability to inhibit virus with mutant enzyme...
  21. ncbi request reprint Monitoring the development of non-nucleoside reverse transcriptase inhibitor-associated resistant HIV-1 using an electrochemiluminescence-based reverse transcriptase polymerase assay
    Vandna Munshi
    Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19486, USA
    Anal Biochem 374:121-32. 2008
    ..The magnitude of resistance of the resulting mutant viruses was assessed directly by the assay, eliminating the need for cloning, expressing, and purifying the RT mutants...
  22. ncbi request reprint PD-1 blockade in rhesus macaques: impact on chronic infection and prophylactic vaccination
    Adam C Finnefrock
    Vaccine Basic Research, Merck Research Laboratories, West Point, PA 19486, USA
    J Immunol 182:980-7. 2009
    ..05) increase in the peak percentage of T cells specific for the CM9 Gag epitope. These new results on PD-1 blockade in nonhuman primates point to a broader role for PD-1 immunomodulation and to potential applications in humans...
  23. doi request reprint Purification of untagged HIV-1 reverse transcriptase by affinity chromatography
    Meiqing Lu
    Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19486, USA
    Protein Expr Purif 71:231-9. 2010
    ..Untagged RT was released from the column by reductive cleavage of the intein by DTT. These two methods significantly shorten the time required to purify untagged WT and mutant RTs...
  24. doi request reprint Potent and selective HIV-1 ribonuclease H inhibitors based on a 1-hydroxy-1,8-naphthyridin-2(1H)-one scaffold
    Peter D Williams
    Department of Medicinal Chemistry, Merck and Co, Inc, West Point, PA 19486, USA
    Bioorg Med Chem Lett 20:6754-7. 2010
    ..19 μM) with a modest window with respect to cytotoxicity (CC(50)=3.3 μM)...
  25. ncbi request reprint Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques
    Daria J Hazuda
    Department of Biological Chemistry, Merck Research Laboratories, Post Office Box 4, West Point, PA 19486, USA
    Science 305:528-32. 2004
    ..These studies demonstrate integrase inhibitor activity in vivo and suggest that cellular immunity facilitates chemotherapeutic efficacy in retroviral infections...
  26. ncbi request reprint Enhancement of alpha -helicity in the HIV-1 inhibitory peptide DP178 leads to an increased affinity for human monoclonal antibody 2F5 but does not elicit neutralizing responses in vitro. Implications for vaccine design
    Joseph G Joyce
    Department of Virus and Cell Biology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 277:45811-20. 2002
    ..We discuss these findings in terms of structural and immunological considerations as to the utility of a 2F5-like response...
  27. pmc Altering expression levels of human immunodeficiency virus type 1 gp120-gp41 affects efficiency but not kinetics of cell-cell fusion
    Janet E Lineberger
    Department of Biological Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Virol 76:3522-33. 2002
    ..Furthermore, the probability of reaching this threshold is governed, in part, by the surface density of gp120/gp41...
  28. pmc Covalent stabilization of coiled coils of the HIV gp41 N region yields extremely potent and broad inhibitors of viral infection
    Elisabetta Bianchi
    Istituto di Ricerche di Biologia Moleculare P Angeletti, 00040 Pomezia, Rome, Italy
    Proc Natl Acad Sci U S A 102:12903-8. 2005
    ..These features make (CCIZN17)3 an attractive lead to develop as an antiviral drug, alone or in combination with DP178, as well as a promising immunogen to elicit a fusion-blocking neutralizing antibody response...
  29. ncbi request reprint Structural analysis of the epitope of the anti-HIV antibody 2F5 sheds light into its mechanism of neutralization and HIV fusion
    Gaetano Barbato
    Istituto di Ricerche di Biologia Molecolare P Angeletti IRBM, Via Pontina Km 30 600, 00040 Pomezia, Rome, Italy
    J Mol Biol 330:1101-15. 2003
    ..At the same time, our hypothesis offers a structural explanation for the mechanism of neutralization of mAb 2F5...
  30. ncbi request reprint Tetrazole thioacetanilides: potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant
    Ester Muraglia
    Department of Medicinal Chemistry, IRBM MRL Rome, Via Pontina Km 30, 600, 00040 Pomezia, Rome, Italy
    Bioorg Med Chem Lett 16:2748-52. 2006
    ..Extensive SAR investigation led to potent compounds, with nanomolar activity on K103N, and orally bioavailable in rats...
  31. pmc In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor
    Ming Tain Lai
    Merck Research Laboratories, West Point, Pennsylvania, USA
    Antimicrob Agents Chemother 58:1652-63. 2014
    ..Taken together, these in vitro data suggest that MK-1439 possesses the desired properties for further development as a new antiviral agent. ..
  32. doi request reprint Raltegravir: the first HIV-1 integrase strand transfer inhibitor in the HIV armamentarium
    Bach Yen T Nguyen
    ISENTRESS Discovery and Development Team, Merck Research Laboratories, North Wales, Pennsylvania 19454 1099, USA
    Ann N Y Acad Sci 1222:83-9. 2011
    ..Raltegravir represents an important addition to the current armamentarium for the treatment of HIV infection...
  33. pmc Small molecule mimetics of an HIV-1 gp41 fusion intermediate as vaccine leads
    Michael J Caulfield
    Department of Vaccine Basic Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 285:40604-11. 2010
    ....
  34. ncbi request reprint Automated high-throughput purification of antibody fragments to facilitate evaluation in functional and kinetic based assays
    Bin Su
    Department of Vaccines and Biologics Research, Merck Research Laboratories, 770 Sumneytown Pike, P O Box 4, West Point, PA 19486, USA
    J Immunol Methods 322:94-103. 2007
    ..The assay results from these purified samples were used to prioritize candidates before converting them to IgG. This protocol can process up to 300 small-scale and up to 72 large-scale scFvs or Fabs per week per full-time employee (FTE)...
  35. ncbi request reprint Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs)
    Zhijian Zhao
    Department of Medicinal Chemistry, Merck and Co, Inc, PO Box 4, West Point, PA 19486, USA
    Bioorg Med Chem Lett 18:554-9. 2008
    ..This Letter describes the design, synthesis, and biological evaluation of novel 3-indole sulfonamides as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) with balanced profiles against common HIV RT mutants K103N and Y181C...
  36. ncbi request reprint Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 1: Discovery and SAR study of 4-pyrazolylpiperidine side chains
    Dong Ming Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 14:935-9. 2004
    ..Truncation of a benzyl group to a phenyl group afforded compounds with dramatically improved oral bioavailability, albeit with reduced activity...
  37. ncbi request reprint Potential new therapies for the treatment of HIV-1 infection
    Jon H Condra
    Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Annu Rev Med 53:541-55. 2002
    ..This brief review describes the current state of this search as well as potentially novel viral targets for chemotherapeutic intervention...
  38. ncbi request reprint Inhibition of HIV-1 ribonuclease H by a novel diketo acid, 4-[5-(benzoylamino)thien-2-yl]-2,4-dioxobutanoic acid
    Cathryn A Shaw-Reid
    Department of Biological Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486 0004, USA
    J Biol Chem 278:2777-80. 2003
    ....
  39. doi request reprint Determination of clinically relevant cutoffs for HIV-1 phenotypic resistance estimates through a combined analysis of clinical trial and cohort data
    Bart Winters
    Virco BVBA, Mechelen, Belgium
    J Acquir Immune Defic Syndr 48:26-34. 2008
    ..Clinically relevant cutoffs are needed for the interpretation of HIV-1 phenotypic resistance estimates as predicted by "virtual" phenotype HIV resistance analysis...
  40. ncbi request reprint Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database
    Damian J McColl
    Gilead Sciences, Foster City, CA 94404, USA
    Antivir Ther 13:189-97. 2008
    ..Nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations (NAMs) can affect response to treatment with NRTIs and might also result in HIV-1 with reduced replication capacity...
  41. ncbi request reprint The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V
    John K Ly
    Gilead Sciences, Inc, Foster City, CA, USA
    Antivir Chem Chemother 18:307-16. 2007
    ..The K65R-mediated effect on decreasing NRTI excision was stronger than for M184V. These studies show that both mechanisms of resistance (binding/incorporation and excision) must be considered when defining resistance mechanisms...
  42. pmc Nef does not affect the efficiency of human immunodeficiency virus type 1 fusion with target cells
    Minoru Tobiume
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2363, USA
    J Virol 77:10645-50. 2003
    ..We conclude that Nef acts at a postentry step in infection, probably by facilitating intracellular transport of the HIV-1 ribonucleoprotein complex...
  43. pmc Simian immunodeficiency virus SIVagm dynamics in African green monkeys
    Ivona Pandrea
    Division of Comparative Pathology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA
    J Virol 82:3713-24. 2008
    ....
  44. pmc Short-lived infected cells support virus replication in sooty mangabeys naturally infected with simian immunodeficiency virus: implications for AIDS pathogenesis
    Shari N Gordon
    University of Pennsylvania School of Medicine, 705 Stellar Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19143, USA
    J Virol 82:3725-35. 2008
    ....
  45. doi request reprint Genetic basis of variation in tenofovir drug susceptibility in HIV-1
    Robert J Murray
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland, UK
    AIDS 22:1113-23. 2008
    ..To develop an improved model for the genetic basis of reduced susceptibility to tenofovir in vitro...
  46. doi request reprint The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation
    Evguenia S Svarovskaia
    Gilead Sciences, Inc, 4 University Place, 4611 University Drive, Durham, NC 27707, USA
    J Acquir Immune Defic Syndr 48:428-36. 2008
    ..In clinical isolates, K65R is frequently accompanied by the A62V and S68G reverse transcriptase mutations...
  47. doi request reprint Raltegravir with optimized background therapy for resistant HIV-1 infection
    Roy T Steigbigel
    State University of New York at Stony Brook, Stony Brook, USA
    N Engl J Med 359:339-54. 2008
    ..Raltegravir (MK-0518) is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase active against HIV-1 susceptible or resistant to older antiretroviral drugs...
  48. ncbi request reprint Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection: a randomized trial
    Kathleen Squires
    Keck School of Medicine, University of Southern California, Los Angeles, USA
    Ann Intern Med 139:313-20. 2003
    ..Resistance to antiretroviral agents remains a leading cause of treatment failure for patients infected with HIV-1...
  49. pmc Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity
    Kirsten L White
    Gilead Sciences, Foster City, California 94404 ViroLogic, Inc, South San Francisco, California 94080, USA
    Antimicrob Agents Chemother 46:3437-46. 2002
    ....
  50. ncbi request reprint Resistance surveillance in chronic hepatitis B patients treated with adefovir dipivoxil for up to 60 weeks
    Huiling Yang
    Gilead Sciences Inc, Foster City, CA 94404, USA
    Hepatology 36:464-73. 2002
    ..In conclusion, these results, although based on a limited number of patients, suggest that treatment with ADV does not lead to the emergence of resistant virus after up to 60 weeks of therapy...
  51. pmc ATP-dependent removal of nucleoside reverse transcriptase inhibitors by human immunodeficiency virus type 1 reverse transcriptase
    Lisa K Naeger
    Gilead Sciences, Inc, Foster City, California 94404, USA
    Antimicrob Agents Chemother 46:2179-84. 2002
    ..The minimal removal of abacavir, ddC, DAPD, 3TC, ddI, and tenofovir is consistent with the minor changes in susceptibility to these drugs observed for HIV mutants with thymidine analog resistance mutations...
  52. ncbi request reprint Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study
    Robert T Schooley
    University of Colorado, Denver, Colorado, USA
    AIDS 16:1257-63. 2002
    ..To evaluate the safety and efficacy of once daily doses of tenofovir DF (TDF) administered in combination with other antiretroviral therapy (ART) in treatment-experienced HIV-1-infected patients with incomplete virological suppression...
  53. ncbi request reprint Genotypic and phenotypic analyses of HIV-1 in antiretroviral-experienced patients treated with tenofovir DF
    Nicolas A Margot
    Gilead Sciences, Inc, Foster City, California 94404, USA
    AIDS 16:1227-35. 2002
    ..To evaluate the virologic responses and mutational profiles in antiretroviral-experienced patients adding tenofovir DF once-daily to their existing regimens...
  54. ncbi request reprint A comparison of the phenotypic susceptibility profiles of emtricitabine and lamivudine
    Katyna Borroto-Esoda
    Gilead Sciences, Inc, Foster City, CA, USA
    Antivir Chem Chemother 18:297-300. 2007
    ..FTC and 3TC demonstrate nearly identical phenotypic resistance profiles and have the same biological cutoff in this panel of NRTI-R and WT clinical HIV-1 isolates...
  55. ncbi request reprint Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations
    Jerome Deval
    Architecture et Fonction des Macromolecules Biologiques, UMR 6098 CNRS et Université Aix Marseille I et II, ESIL, Campus de Luminy, 13288 Marseille Cedex 09, France
    J Biol Chem 279:509-16. 2004
    ..All together, these results define at the molecular level how nucleoside-resistant viruses can be driven to reduced viral fitness...
  56. ncbi request reprint Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine
    Evguenia S Svarovskaia
    Gilead Sciences, Inc, Durham, NC, USA
    J Acquir Immune Defic Syndr 46:174-80. 2007
    ..Prior abacavir (ABC) or didanosine (ddI) therapy can result in the L74V/I or K65R mutation in HIV-1 reverse transcriptase. Preexisting K65R may have an impact on the treatment response to tenofovir disoproxil fumarate (TDF)...
  57. ncbi request reprint SIV-specific T lymphocyte responses in PBMC and lymphoid tissues of SIV-infected pigtailed macaques during suppressive combination antiretroviral therapy
    Lucy M Carruth
    Department of Comparative Medicine, Johns Hopkins University School of Medicine, Jefferson Street Building, 600 N Wolfe Street, Baltimore, MD 21287, USA
    J Med Primatol 34:109-21. 2005
    ..Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response...
  58. pmc Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation
    Jan Weber
    Cleveland Clinic Foundation, Lerner Research Institute, Department of Molecular Genetics, Section Virology NN10, 9500 Euclid Ave, Cleveland, OH 44195, USA
    J Clin Microbiol 43:1395-400. 2005
    ..These results support a reduction in in vivo replication for K65R mutant viruses...
  59. ncbi request reprint Predictors of residual viremia in HIV-infected patients successfully treated with efavirenz and lamivudine plus either tenofovir or stavudine
    Diane V Havlir
    Department of Medicine, San Francisco General Hospital, University of California at San Francisco, San Francisco, California, USA
    J Infect Dis 191:1164-8. 2005
    ..05). However, a level of residual viremia <50 copies/mL was not associated with CD4 cell count changes or risk of virologic rebound through 72 weeks of follow-up...
  60. pmc Coupling of human immunodeficiency virus type 1 fusion to virion maturation: a novel role of the gp41 cytoplasmic tail
    Donald J Wyma
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    J Virol 78:3429-35. 2004
    ..This "inside-out" regulation of HIV-1 fusion could play an important role in the virus life cycle by preventing the entry of immature, noninfectious particles...
  61. ncbi request reprint Synthesis and biological evaluation of 5R- and 5S-methyl substituted D- and L-configuration 1,3-dioxolane nucleoside analogs
    Sanjib Bera
    Department of Medicinal Chemistry, Isis Pharmaceuticals, Carlsbad, CA 92008, USA
    Bioorg Med Chem 12:6237-47. 2004
    ..In addition, activity against vaccinia and HIV was evaluated in cell-based assays. The 2-hydroxymethyl-5-methyl-1,3-dioxolanes were found to be inactive...
  62. pmc Murine T cells potently restrict human immunodeficiency virus infection
    Jörg G Baumann
    HIV Drug Resistance Program, Bldg 535, Rm 123, National Cancer Institute at Frederick, Frederick, MD 21702 1201, USA
    J Virol 78:12537-47. 2004
    ..Further studies of this newly identified block may lend insight into the early events of retroviral replication and reveal new targets for antiretroviral interventions...
  63. ncbi request reprint Patterns of resistance emerging in HIV-1 from antiretroviral-experienced patients undergoing intensification therapy with tenofovir disoproxil fumarate
    Damian J McColl
    Gilead Sciences, Inc, Foster City, CA 94404, USA
    J Acquir Immune Defic Syndr 37:1340-50. 2004
    ..Therefore, intensification with once-daily tenofovir DF therapy resulted in a sustained reduction in HIV-1 viral load and a low risk for development of the K65R mutation in this treatment-experienced patient population...
  64. pmc Development of Vgamma2Vdelta2+ T cell responses during active mycobacterial coinfection of simian immunodeficiency virus-infected macaques requires control of viral infection and immune competence of CD4+ T cells
    Ling Shen
    Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    J Infect Dis 190:1438-47. 2004
    ....
  65. ncbi request reprint K65R, TAMs and tenofovir
    Michael D Miller
    Gilead Sciences, Inc, Foster City, CA 94404, USA
    AIDS Rev 6:22-33. 2004
    ..Thus, the K65R mutation appears manageable for the sequencing of treatment regimens in the case of its development...
  66. ncbi request reprint Extended treatment with tenofovir disoproxil fumarate in treatment-experienced HIV-1-infected patients: genotypic, phenotypic, and rebound analyses
    Nicolas A Margot
    Gilead Sciences, Goster City, California 94404, USA
    J Acquir Immune Defic Syndr 33:15-21. 2003
    ....
  67. pmc Molecular mechanisms of tenofovir resistance conferred by human immunodeficiency virus type 1 reverse transcriptase containing a diserine insertion after residue 69 and multiple thymidine analog-associated mutations
    Kirsten L White
    Gilead Sciences, Foster City, California, 94404, USA
    Antimicrob Agents Chemother 48:992-1003. 2004
    ..Computer modeling suggests that the increased mobility of the beta3-beta4 loop may contribute to the high-level and broad NRTI resistance caused by the T69 insertion mutation...
  68. ncbi request reprint A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT
    Kirsten L White
    Gilead Sciences Inc Foster City, California 94404, USA
    AIDS 19:1751-60. 2005
    ..To determine the mechanisms of resistance of K65R mutant reverse transcriptase (RT) to the currently approved nucleoside and nucleotide RT inhibitors (NRTI)...
  69. pmc Effects of the translocation status of human immunodeficiency virus type 1 reverse transcriptase on the efficiency of excision of tenofovir
    Bruno Marchand
    Department of Microbiology and Immunology, McGill University, Lyman Duff Medical Building, Montreal, QC, Canada
    Antimicrob Agents Chemother 51:2911-9. 2007
    ....
  70. ncbi request reprint Long-term follow-up of patients taking tenofovir DF with low-level HIV-1 viremia and the K65R substitution in HIV-1 RT
    Brandi J Chappell
    Gilead Sciences, Inc, Foster City, California 94404, USA
    AIDS 21:761-3. 2007
    ..Over 18 months, no patient developed multinucleoside resistance (Q151M or T69 insertions) and plasma viral loads were stable (median +0.04 log10 copies/ml)...
  71. ncbi request reprint K65R development among subtype C HIV-1-infected patients in tenofovir DF clinical trials
    Michael D Miller
    AIDS 21:265-6. 2007
  72. pmc The hepatitis B virus polymerase mutation rtV173L is selected during lamivudine therapy and enhances viral replication in vitro
    William E Delaney
    Gilead Sciences Inc, Foster City, California 94404, USA
    J Virol 77:11833-41. 2003
    ..Together, these results suggest that rtV173L is a compensatory mutation that is selected in lamivudine-resistant patients due to an enhanced replication phenotype...
  73. pmc Highly uneven distribution of tenofovir-selected simian immunodeficiency virus in different anatomical sites of rhesus macaques
    Magdalena Magierowska
    Department of Medicine, University of California San Francisco, California 94118, USA
    J Virol 78:2434-44. 2004
    ....
  74. ncbi request reprint The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations
    Kirsten L White
    Gilead Sciences, Inc, Foster City, CA, USA
    Antivir Ther 11:155-63. 2006
    ....
  75. ncbi request reprint Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients
    Michael D Miller
    Gilead Sciences, Foster City, California 94404, USA
    J Infect Dis 189:837-46. 2004
    ..The results from these controlled clinical trials provide guidance for the use of tenofovir DF for treatment-experienced patients...
  76. ncbi request reprint Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial
    Joel E Gallant
    Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    JAMA 292:191-201. 2004
    ..Tenofovir disoproxil fumarate (DF) is a once-daily nucleotide analogue reverse transcriptase inhibitor...