Michael D Miller

Summary

Affiliation: Gilead Sciences
Country: USA

Publications

  1. ncbi Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity
    M D Miller
    Gilead Sciences, Foster City, California 94404, USA
    Mol Pharmacol 54:291-7. 1998
  2. ncbi Human immunodeficiency virus type 1 expressing the lamivudine-associated M184V mutation in reverse transcriptase shows increased susceptibility to adefovir and decreased replication capability in vitro
    M D Miller
    Gilead Sciences, Foster City, California, USA
    J Infect Dis 179:92-100. 1999
  3. ncbi Adefovir and tenofovir susceptibilities of HIV-1 after 24 to 48 weeks of adefovir dipivoxil therapy: genotypic and phenotypic analyses of study GS-96-408
    M D Miller
    Gilead Sciences, Inc, 333 Lakeside Dr, Foster City, CA 94404, U S A
    J Acquir Immune Defic Syndr 27:450-8. 2001
  4. ncbi K65R, TAMs and tenofovir
    Michael D Miller
    Gilead Sciences, Inc, Foster City, CA 94404, USA
    AIDS Rev 6:22-33. 2004
  5. ncbi 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
  6. ncbi 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
  7. ncbi 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
  8. ncbi Development of HIV-1 drug resistance through 144 weeks in antiretroviral-naïve subjects on emtricitabine, tenofovir disoproxil fumarate, and efavirenz compared with lamivudine/zidovudine and efavirenz in study GS-01-934
    Nicolas A Margot
    Gilead Sciences, Inc, Foster City, California 94404, USA
    J Acquir Immune Defic Syndr 52:209-21. 2009
  9. ncbi The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study
    Joy Y Feng
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, California 94404, USA
    Retrovirology 6:44. 2009
  10. ncbi 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

Detail Information

Publications81

  1. ncbi Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity
    M D Miller
    Gilead Sciences, Foster City, California 94404, USA
    Mol Pharmacol 54:291-7. 1998
    ..These results with recombinant K70E RT are consistent with the reduced in vitro replication capacity of the K70E RT mutant of HIV-1 and further demonstrate that the K70E mutation confers minor PMEA and 3TC resistance to HIV-1...
  2. ncbi Human immunodeficiency virus type 1 expressing the lamivudine-associated M184V mutation in reverse transcriptase shows increased susceptibility to adefovir and decreased replication capability in vitro
    M D Miller
    Gilead Sciences, Foster City, California, USA
    J Infect Dis 179:92-100. 1999
    ..These studies suggest that patients possessing HIV with zidovudine and lamivudine resistance mutations may benefit from adefovir dipivoxil therapy...
  3. ncbi Adefovir and tenofovir susceptibilities of HIV-1 after 24 to 48 weeks of adefovir dipivoxil therapy: genotypic and phenotypic analyses of study GS-96-408
    M D Miller
    Gilead Sciences, Inc, 333 Lakeside Dr, Foster City, CA 94404, U S A
    J Acquir Immune Defic Syndr 27:450-8. 2001
    ..To determine whether genotypic changes in HIV-1 (HIV) reverse transcriptase (RT) occur during adefovir dipivoxil (ADV) therapy that may alter the susceptibility of HIV to adefovir or the related nucleotide inhibitor, tenofovir...
  4. ncbi 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...
  5. ncbi 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...
  6. ncbi 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...
  7. ncbi 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...
  8. ncbi Development of HIV-1 drug resistance through 144 weeks in antiretroviral-naïve subjects on emtricitabine, tenofovir disoproxil fumarate, and efavirenz compared with lamivudine/zidovudine and efavirenz in study GS-01-934
    Nicolas A Margot
    Gilead Sciences, Inc, Foster City, California 94404, USA
    J Acquir Immune Defic Syndr 52:209-21. 2009
    ..Baseline NNRTI-R was significantly associated with virologic failure in both groups (P < 0.001)...
  9. ncbi The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study
    Joy Y Feng
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, California 94404, USA
    Retrovirology 6:44. 2009
    ....
  10. ncbi 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...
  11. ncbi Anti-hepatitis B virus activity in vitro of combinations of tenofovir with nucleoside/nucleotide analogues
    Yuao Zhu
    Gilead Sciences, Inc, Durham, NC, USA
    Antivir Chem Chemother 19:165-76. 2009
    ..We therefore evaluated the in vitro anti-HBV activity of tenofovir (TFV), the active parent drug of TDF, combined with FTC, 3TC, ETV, LdT and adefovir (AFV)...
  12. ncbi Week 48 resistance surveillance in two phase 3 clinical studies of adefovir dipivoxil for chronic hepatitis B
    Christopher E Westland
    Gilead Sciences, Inc, Foster City, CA
    Hepatology 38:96-103. 2003
    ..In conclusion, no adefovir resistance mutations were identified in a large group of chronic hepatitis B patients treated with ADV for 48 weeks...
  13. ncbi 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)...
  14. ncbi 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
    ....
  15. ncbi 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...
  16. ncbi Mutations in the thumb-connection and RNase H domain of HIV type-1 reverse transcriptase of antiretroviral treatment-experienced patients
    Joshua M Waters
    Gilead Sciences, Inc, Durham, NC, USA
    Antivir Ther 14:231-9. 2009
    ..Antiretroviral therapy that targets HIV type-1 (HIV-1) reverse transcriptase (RT) can be linked to mutations in the thumb-connection (amino acids [AA] 241-426) and RNase H (AA 427-560) domains, which could affect drug resistance...
  17. ncbi 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)...
  18. ncbi Phenotypic susceptibility to bevirimat in isolates from HIV-1-infected patients without prior exposure to bevirimat
    Nicolas A Margot
    Gilead Sciences, Inc, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 54:2345-53. 2010
    ..Our results should be helpful in the design of diagnostics for prediction of the potential benefit of BVM treatment in HIV-1-infected patients...
  19. ncbi 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...
  20. ncbi 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
    ....
  21. ncbi 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)...
  22. ncbi 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...
  23. ncbi 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...
  24. ncbi 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...
  25. ncbi Reduced emergence of the M184V/I resistance mutation when antiretroviral-naïve subjects use emtricitabine versus lamivudine in regimens composed of two NRTIs plus the NNRTI efavirenz
    Damian J McColl
    Gilead Sciences, Inc, Foster City, CA, USA
    HIV Clin Trials 12:61-70. 2011
    ....
  26. ncbi Abundant drug-resistant NS3 mutants detected by deep sequencing in hepatitis C virus-infected patients undergoing NS3 protease inhibitor monotherapy
    Evguenia S Svarovskaia
    Gilead Sciences, Inc, Foster City, CA, USA
    J Clin Microbiol 50:3267-74. 2012
    ..6 to 3.8 log(10) with NS3 protease inhibitor monotherapy that does not suppress the identified preexisting NS3 DRMs and thus a need for a combination therapy...
  27. ncbi Trends in HIV-1 reverse transcriptase resistance-associated mutations and antiretroviral prescription data from 2003-2010
    Michael D Miller
    Gilead Sciences, Inc, Foster City, CA, USA
    Antivir Ther 17:993-9. 2012
    ..Emtricitabine (FTC) or lamivudine (3TC), components of recommended initial ARV regimens, are structurally related and share the same resistance mutation (M184V/I). However they differ with respect to potency and incidence of M184V/I...
  28. ncbi 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...
  29. ncbi 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
    ..In addition, there was a low incidence of genotypic or phenotypic resistance to tenofovir DF arising during 48 weeks of therapy...
  30. ncbi 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
    ....
  31. ncbi Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virus
    William E Delaney
    Gilead Sciences Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 50:2471-7. 2006
    ..Overall, the antiviral and metabolic profile of tenofovir supports its development for the treatment of chronic hepatitis B...
  32. ncbi 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...
  33. ncbi No resistance to tenofovir disoproxil fumarate detected after up to 144 weeks of therapy in patients monoinfected with chronic hepatitis B virus
    Andrea Snow-Lampart
    Gilead Sciences, Incorporated, Durham, NC, USA
    Hepatology 53:763-73. 2011
    ..CONCLUSION: No nucleoside-naive or nucleoside-experienced patient developed HBV pol/RT mutations associated with TDF resistance after up to 144 weeks of exposure to TDF monotherapy...
  34. ncbi Characterization of resistance to the protease inhibitor GS-9451 in hepatitis C virus-infected patients
    Hadas Dvory-Sobol
    Gilead Sciences, Foster City, California, USA
    Antimicrob Agents Chemother 56:5289-95. 2012
    ..The lack of cross-resistance between GS-9451 and other classes of HCV inhibitors supports the utility of combination therapy...
  35. ncbi Tegobuvir (GS-9190) potency against HCV chimeric replicons derived from consensus NS5B sequences from genotypes 2b, 3a, 4a, 5a, and 6a
    Kelly A Wong
    Department of Clinical Virology, Gilead Sciences, Inc, Foster City, CA 94404, USA
    Virology 429:57-62. 2012
    ..These data support the use of HCV chimeras in profiling direct acting antivirals across genotypes and specifically determines the impact of the C445F NS5B polymorphism on tegobuvir potency against genotypes 3a, 4a, and 6a...
  36. ncbi Combinations of adefovir with nucleoside analogs produce additive antiviral effects against hepatitis B virus in vitro
    William E Delaney
    Gilead Sciences, Inc, Foster City, CA 94402, USA
    Antimicrob Agents Chemother 48:3702-10. 2004
    ..There was no evidence of cytotoxicity with any of the drugs when used alone or in combination at the tested doses...
  37. ncbi In vitro combination studies of tenofovir and other nucleoside analogues with ribavirin against HIV-1
    Nicolas A Margot
    Gilead Sciences, Inc, Foster City, CA, USA
    Antivir Ther 10:343-8. 2005
    ..These results suggest a low potential for increased toxicity upon co-administration of tenofovir DF with RBV in patients...
  38. ncbi In vitro drug susceptibility analysis of hepatitis B virus clinical quasispecies populations
    Yuao Zhu
    Gilead Sciences, Inc, 4611 University Drive, Durham, NC 27707, USA
    J Clin Microbiol 45:3335-41. 2007
    ....
  39. ncbi Pooled analysis of amino acid changes in the HBV polymerase in patients from four major adefovir dipivoxil clinical trials
    Katyna Borroto-Esoda
    Department of Clinical Virology, Gilead Sciences, Inc, 4 University Place, 4611 University Dr, Durham, NC 27707, USA
    J Hepatol 47:492-8. 2007
    ..Recent reports have proposed other ADV resistance (ADV-R) mutations. The aims of this study were to confirm the role of rtA181V and rtN236T in clinical resistance to ADV and to screen for other potential ADV-R mutations...
  40. ncbi Allele-specific real-time PCR system for detection of subpopulations of genotype 1a and 1b hepatitis C NS5B Y448H mutant viruses in clinical samples
    Andrew S Bae
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    J Clin Microbiol 49:3168-74. 2011
    ..5% to 3.0% detected in 5/62 (8%) treatment-naïve patient samples. These findings suggest the need for combination therapy with HCV-specific inhibitors to avoid viral rebound of preexisting mutant HCV...
  41. ncbi Lack of a metabolic and antiviral drug interaction between tenofovir, abacavir and lamivudine
    Adrian S Ray
    Gilead Sciences, Inc, Foster City, CA, USA
    Antivir Ther 10:451-7. 2005
    ..Design: Procedures were developed to evaluate the in vitro metabolism and antiviral activity of drug combinations of TFV, ABC and 3TC in cell types relevant for HIV infection...
  42. ncbi Effect of nucleoside and nucleotide reverse transcriptase inhibitors of HIV on endogenous nucleotide pools
    Jennifer E Vela
    Department of Preclinical Drug Metabolism, Gilead Sciences, Inc, Foster City, CA, USA
    Antivir Ther 13:789-97. 2008
    ..In vitro studies were performed in order to understand the effect of N(t)RTIs on endogenous nucleotide pools...
  43. ncbi The use of tenofovir disoproxil fumarate for the treatment of nucleoside-resistant HIV-1
    Damian J McColl
    Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA
    J Antimicrob Chemother 51:219-23. 2003
  44. ncbi 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...
  45. ncbi In vitro resistance selections using elvitegravir, raltegravir, and two metabolites of elvitegravir M1 and M4
    Nicolas A Margot
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    Antiviral Res 93:288-96. 2012
    ....
  46. ncbi MultiCode-RTx real-time PCR system for detection of subpopulations of K65R human immunodeficiency virus type 1 reverse transcriptase mutant viruses in clinical samples
    Evguenia S Svarovskaia
    Gilead Sciences, Inc, 4 University Place, 4611 University Drive, Durham, NC 27707, USA
    J Clin Microbiol 44:4237-41. 2006
    ..Fifty-three treatment-naïve and 20 treatment-experienced specimens were successfully genotyped with the new method. Results were in agreement with population sequencing and the labor-intensive single-genome sequencing method...
  47. ncbi The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness
    Rima Kulkarni
    Clinical Virology, Gilead Sciences, Inc, Foster City, CA, USA
    J Acquir Immune Defic Syndr 59:47-54. 2012
    ..Eighty percent of subjects used emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF); a single tablet regimen of FTC/RPV/TDF is in development...
  48. ncbi Susceptibility of treatment-naive hepatitis C virus (HCV) clinical isolates to HCV protease inhibitors
    Andrew Bae
    Department of Clinical Virology, Gilead Sciences, 333 Lakeside Dr, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 54:5288-97. 2010
    ..Our results suggest that the natural variation in baseline susceptibility may contribute to different degrees of antiviral response among patients in vivo, particularly at lower doses...
  49. ncbi 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...
  50. ncbi 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
    ..CONCLUSION: In treatment-experienced patients with suboptimal viral suppression, tenofovir DF significantly reduced HIV-1 RNA level and had a safety profile similar to that of placebo...
  51. ncbi 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...
  52. ncbi 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...
  53. ncbi 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...
  54. ncbi 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...
  55. ncbi 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
    ..CONCLUSIONS: In treatment-experienced patients with baseline nucleoside resistance mutations, TDF provided dose-related, durable reductions in HIV-1 RNA. Through 24 weeks, the safety profile of TDF was similar to that of placebo...
  56. ncbi 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
    ....
  57. ncbi 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
    ....
  58. ncbi 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 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
    ....
  60. ncbi 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...
  61. ncbi Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naive and -experienced patients coinfected with HIV-1 and hepatitis B virus
    Gregory J Dore
    National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia
    J Infect Dis 189:1185-92. 2004
    ..Lamivudine has potent activity against both HIV-1 and HBV; however, lamivudine-resistance mutations in HBV frequently develop...
  62. ncbi 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...
  63. ncbi 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...
  64. ncbi 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...
  65. ncbi 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...
  66. ncbi 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...
  67. ncbi 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
    ....
  68. ncbi 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...
  69. ncbi 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...
  70. ncbi 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...
  71. ncbi 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...
  72. ncbi 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...
  73. ncbi 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
    ....
  74. ncbi 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...
  75. ncbi Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study
    Martin Markowitz
    Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY, USA
    J Acquir Immune Defic Syndr 46:125-33. 2007
    ..This study explored the antiretroviral activity and safety of raltegravir in treatment-naive patients with plasma HIV-1 RNA levels > or = 5000 copies/mL and CD4 T-cell counts > or = 100 cells/mm...
  76. ncbi 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...
  77. ncbi 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
    ....
  78. ncbi Structures of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir
    Steve Tuske
    Center for Advanced Biotechnology and Medicine and Rutgers University Department of Chemistry and Chemical Biology, 679 Hoes Lane, Piscataway, New Jersey 08854-5638, USA
    Nat Struct Mol Biol 11:469-74. 2004
    ..HIV-1 RT resistance mechanisms to AZT and 3TC take advantage of these handles; tenofovir's structure lacks handles that could protrude through the substrate envelope to cause resistance...
  79. ncbi K65R development among subtype C HIV-1-infected patients in tenofovir DF clinical trials
    Michael D Miller
    AIDS 21:265-6. 2007
  80. ncbi 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...
  81. ncbi 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
    ....