reverse transcriptase inhibitors

Summary

Summary: Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.

Top Publications

  1. pmc Effect of reverse transcriptase inhibitors on LINE-1 and Ty1 reverse transcriptase activities and on LINE-1 retrotransposition
    Lixin Dai
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    BMC Biochem 12:18. 2011
  2. pmc The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy
    Mina C Hosseinipour
    University of North Carolina Project, Lilongwe, Malawi
    AIDS 23:1127-34. 2009
  3. ncbi Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial
    Calvin J Cohen
    Community Research Initiative of New England, Boston, MA 02215, USA
    Lancet 378:229-37. 2011
  4. pmc Association of abacavir and impaired endothelial function in treated and suppressed HIV-infected patients
    Priscilla Y Hsue
    Division of Cardiology, Positive Health Program of the Department of Medicine, San Francisco General Hospital, University of California San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110, USA
    AIDS 23:2021-7. 2009
  5. 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
  6. ncbi Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study
    F van Leth
    International Antiviral Therapy Evaluation Center, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
    Lancet 363:1253-63. 2004
  7. ncbi Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients
    C Marzolini
    Department of Medicine, University Hospital of Lausanne, Switzerland
    AIDS 15:71-5. 2001
  8. pmc Class-sparing regimens for initial treatment of HIV-1 infection
    Sharon A Riddler
    University of Pittsburgh, Pittsburgh, USA
    N Engl J Med 358:2095-106. 2008
  9. pmc N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance
    Soo Huey Yap
    Molecular Interactions Group, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia
    PLoS Med 4:e335. 2007
  10. pmc Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility
    George L Melikian
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USA
    Antimicrob Agents Chemother 56:2305-13. 2012

Detail Information

Publications293 found, 100 shown here

  1. pmc Effect of reverse transcriptase inhibitors on LINE-1 and Ty1 reverse transcriptase activities and on LINE-1 retrotransposition
    Lixin Dai
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    BMC Biochem 12:18. 2011
    ..Full-length L1 encodes two open reading frames (ORF1, ORF2) and ORF2 has reverse transcriptase activity...
  2. pmc The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy
    Mina C Hosseinipour
    University of North Carolina Project, Lilongwe, Malawi
    AIDS 23:1127-34. 2009
    ..We evaluated drug resistance patterns among patients failing first-line ART on the basis of clinical or immunological criteria in Lilongwe and Blantyre, Malawi...
  3. ncbi Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial
    Calvin J Cohen
    Community Research Initiative of New England, Boston, MA 02215, USA
    Lancet 378:229-37. 2011
    ..We aimed to assess non-inferiority of rilpivirine to efavirenz in a phase 3 trial with common background nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs).
  4. pmc Association of abacavir and impaired endothelial function in treated and suppressed HIV-infected patients
    Priscilla Y Hsue
    Division of Cardiology, Positive Health Program of the Department of Medicine, San Francisco General Hospital, University of California San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110, USA
    AIDS 23:2021-7. 2009
    ..As endothelial dysfunction is central to the pathogenesis of atherosclerosis, we tested the hypothesis that current treatment with abacavir is associated with impaired endothelial function...
  5. 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...
  6. ncbi Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study
    F van Leth
    International Antiviral Therapy Evaluation Center, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
    Lancet 363:1253-63. 2004
    ..The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz...
  7. ncbi Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients
    C Marzolini
    Department of Medicine, University Hospital of Lausanne, Switzerland
    AIDS 15:71-5. 2001
    ..The important inter-individual variability in efavirenz levels strongly argues for dose adjustment on the basis of therapeutic drug monitoring to optimize treatment...
  8. pmc Class-sparing regimens for initial treatment of HIV-1 infection
    Sharon A Riddler
    University of Pittsburgh, Pittsburgh, USA
    N Engl J Med 358:2095-106. 2008
    ..The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs...
  9. pmc N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance
    Soo Huey Yap
    Molecular Interactions Group, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia
    PLoS Med 4:e335. 2007
    ..The objective of this multidisciplinary study was to establish the in vivo relevance of this mutation and its role in drug resistance...
  10. pmc Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility
    George L Melikian
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USA
    Antimicrob Agents Chemother 56:2305-13. 2012
    ....
  11. ncbi Factors influencing efavirenz and nevirapine plasma concentration: effect of ethnicity, weight and co-medication
    Wolfgang Stöhr
    MRC Clinical Trials Unit, London, UK
    Antivir Ther 13:675-85. 2008
    ..The aim of this study was to examine factors influencing plasma concentration of efavirenz and nevirapine...
  12. ncbi Mitochondrial toxicity of NRTI antiviral drugs: an integrated cellular perspective
    William Lewis
    Emory University, Department of Pathology, 1639 Pierce Drive, Room 7117, Atlanta, Georgia 30322, USA
    Nat Rev Drug Discov 2:812-22. 2003
    Highly active antiretroviral therapy (HAART) regimes based on nucleoside reverse transcriptase inhibitors (NRTIs) have revolutionized the treatment of AIDS in recent years...
  13. ncbi Non-nucleoside reverse transcriptase inhibitors (NNRTIs), their discovery, development, and use in the treatment of HIV-1 infection: a review of the last 20 years (1989-2009)
    Marie Pierre de Béthune
    Tibotec BVBA, Generaal De Wittelaan L11 B3, B2800 Mechelen, Belgium
    Antiviral Res 85:75-90. 2010
    ..This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010...
  14. ncbi HIV-1 reverse transcriptase inhibitor resistance mutations and fitness: a view from the clinic and ex vivo
    Javier Martinez-Picado
    Fundacio irsiCaixa, Hospital Germans Trias i Pujol, Ctra de Canyet s n, 08916 Badalona, Spain
    Virus Res 134:104-23. 2008
    ....
  15. ncbi Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging
    Edwin Leeansyah
    Department of Medicine, Monash University, Melbourne, Australia
    J Infect Dis 207:1157-65. 2013
    ..We hypothesized that nucleos(t)ide reverse transcriptase inhibitors (NRTI) may contribute to accelerated aging in HIV-infected individuals on cART via inhibition of ..
  16. pmc Nucleoside analogue reverse transcriptase inhibitors differentially inhibit human LINE-1 retrotransposition
    R Brad Jones
    Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada
    PLoS ONE 3:e1547. 2008
    ..LINE-1 element activity may also play a role in normal physiology...
  17. 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
    ..antiretroviral regimens recommended for treatment-naïve patients include 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)...
  18. ncbi Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy
    K Brinkman
    Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
    Lancet 354:1112-5. 1999
    ....
  19. pmc Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors
    Atsuko Hachiya
    Laboratory of Virus Immunology, Research Center for AIDS, Institute for Virus Research, Kyoto University, 53, Kawaramachi, Shogoin, Sakyo ku, Kyoto 606 8507, Japan
    J Virol 82:3261-70. 2008
    ..showed that N348I conferred multiclass resistance to NNRTIs (NVP and delavirdine) and to nucleoside reverse transcriptase inhibitors (zidovudine [AZT] and didanosine [ddI])...
  20. pmc Natural substrate concentrations can modulate the prophylactic efficacy of nucleotide HIV reverse transcriptase inhibitors
    J Gerardo Garcia-Lerma
    Division of HIV AIDS Prevention, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA
    J Virol 85:6610-7. 2011
    ..identify dATP/TFV-DP ratios as a possible correlate of protection by TFV and suggest that natural substrate concentrations at the mucosa will likely modulate the prophylactic efficacy of nucleotide reverse transcriptase inhibitors.
  21. pmc Dose-response curve slope sets class-specific limits on inhibitory potential of anti-HIV drugs
    Lin Shen
    Department of Medicine, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, Maryland 21205, USA
    Nat Med 14:762-6. 2008
    ..Nucleoside reverse transcriptase inhibitors and integrase inhibitors have slopes of approximately 1, characteristic of noncooperative reactions, ..
  22. ncbi A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase inhibitors
    Bluma Brenner
    McGill University AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada
    AIDS 17:F1-5. 2003
    ..This study evaluates the prevalence of V106 (GTG) and 106M (ATG) codons in clinical isolates as well as the effects of V106M on resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI).
  23. 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...
  24. ncbi Ultra-deep sequencing of HIV-1 reverse transcriptase before start of an NNRTI-based regimen in treatment-naive patients
    Peter Messiaen
    AIDS Reference Laboratory, Ghent University, De Pintelaan 185 9000 Gent, Belgium
    Virology 426:7-11. 2012
    ..Using UDPS, we could not confirm an association between the presence of low minority variants harbouring RT mutations at the start of therapy and primary or secondary therapeutic failure...
  25. ncbi HIV drug resistance
    Francois Clavel
    Unité de Recherche Antivirale, Institut National de la Sante et de la Recherche Medicale, Unité 552, Hopital Bichat Claude Bernard, Paris
    N Engl J Med 350:1023-35. 2004
  26. pmc The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine
    Matthew M Schuckmann
    Christopher Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, Missouri 65211, USA
    J Biol Chem 285:38700-9. 2010
    ..In conclusion, connection subdomain mutation N348I decreases catalytic efficiency and causes in vitro resistance to NVP by decreasing inhibitor binding...
  27. pmc Structural basis of HIV-1 resistance to AZT by excision
    Xiongying Tu
    Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey, USA
    Nat Struct Mol Biol 17:1202-9. 2010
    ..Thus, the resistance mutations create a high-affinity ATP-binding site. The structure of the site provides an opportunity to design inhibitors of AZT-monophosphate excision...
  28. ncbi Switch from protease inhibitor- to efavirenz-based antiretroviral therapy improves quality of life, treatment satisfaction and adherence with low rates of virological failure in virologically suppressed patients
    R E Campo
    Division of Infectious Diseases, Leonard M Miller School of Medicine, University of Miami, 1120 NW14th St, Suite 863, Miami, FL 33136, USA
    Int J STD AIDS 21:166-71. 2010
    ..didanosine (efavirenz-A [QD]) or once-daily efavirenz plus continuation of current nucleoside reverse transcriptase inhibitors (efavirenz-B)...
  29. ncbi Nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase
    Prem L Sharma
    Department of Pediatrics, Laboratory of Biochemical Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA
    Curr Top Med Chem 4:895-919. 2004
    ..The drug cocktail can comprise all three classes of HIV inhibitors, including nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI)...
  30. ncbi Reverse transcriptase inhibitors down-regulate cell proliferation in vitro and in vivo and restore thyrotropin signaling and iodine uptake in human thyroid anaplastic carcinoma
    Matteo Landriscina
    Dipartimento di Scienze Mediche e del Lavoro, Universita degli Studi di Foggia, Viale Pinto, 1 71100 Foggia, Italy
    J Clin Endocrinol Metab 90:5663-71. 2005
    ..Two nonnucleosidic RT inhibitors, efavirenz and nevirapine, currently used in HIV treatment, reversibly down-regulate tumor growth and induce differentiation in several human tumor cell models...
  31. pmc Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission
    Deborah Persaud
    Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    AIDS Res Hum Retroviruses 27:823-9. 2011
    ....
  32. ncbi Increased carotid intima-media thickness in HIV patients treated with protease inhibitors as compared to non-nucleoside reverse transcriptase inhibitors
    Raaj R Sankatsing
    Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Atherosclerosis 202:589-95. 2009
    ..Most markedly, NNRTIs have been associated with increases in high density lipoprotein cholesterol (HDL-C), which may be atheroprotective...
  33. ncbi Effects of nucleoside reverse transcriptase inhibitor backbone on the efficacy of first-line boosted highly active antiretroviral therapy based on protease inhibitors: meta-regression analysis of 12 clinical trials in 5168 patients
    A Hill
    Pharmacology Research Laboratories, University of Liverpool, Liverpool, UK
    HIV Med 10:527-35. 2009
    ..The ACTG 5202 and BICOMBO trials suggested higher efficacy for TDF/FTC, whereas the HEAT trial showed no efficacy difference between the nucleoside reverse transcriptase inhibitor (NRTI) backbones...
  34. 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
    ..immunodeficiency virus (HIV) infections, 19 compounds have been formally approved: (i) the nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine; (ii) ..
  35. ncbi Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts
    Annalise M Martin
    Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia
    AIDS 19:97-9. 2005
    ..These data suggest that HLA-DRB1*0101 and the CD4 status may determine susceptibility to nevirapine hypersensitivity, consistent with a CD4 T-cell-dependent immune response to nevirapine-specific antigens...
  36. ncbi Long-term efficacy and tolerance of efavirenz- and nevirapine-containing regimens in adult HIV type 1 Senegalese patients
    Pierre De Beaudrap
    Hospices Civils de Lyon, Service de Biostatistique, Lyon, F 69424, France
    AIDS Res Hum Retroviruses 24:753-60. 2008
    ..Adverse effects were different between NVP and EFV, but long-term tolerance was good for both. This analysis provided further information on long-term tolerance and efficacy of EFV and NVP in a resource-limited setting...
  37. pmc Induction of T-cell immunity to antiretroviral drug-resistant human immunodeficiency virus type 1
    Ivan Stratov
    Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia
    J Virol 79:7728-37. 2005
    ..This study suggests feasible strategies to further evaluate the potential of limiting antiretroviral drug resistance through induction of T-cell immunity...
  38. ncbi Patient-reported outcomes in virologically suppressed, HIV-1-Infected subjects after switching to a simplified, single-tablet regimen of efavirenz, emtricitabine, and tenofovir DF
    Sally L Hodder
    University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101, USA
    AIDS Patient Care STDS 24:87-96. 2010
    ....
  39. ncbi HIV type 1 genotypic resistance in a clinical database correlates with antiretroviral utilization
    Ron Kagan
    Department of Infectious Diseases, Quest Diagnostics Nichols Institute, San Juan Capistrano, California 92690, USA
    AIDS Res Hum Retroviruses 20:1-9. 2004
    ..Continued monitoring of ARV resistance prevalence, patterns, and utilization trends in clinical databases provides insight into the evolving relationship between clinical practice and ARV resistance...
  40. ncbi Resistance at virological failure using boosted protease inhibitors versus nonnucleoside reverse transcriptase inhibitors as first-line antiretroviral therapy--implications for sustained efficacy of ART in resource-limited settings
    Andrew Hill
    Pharmacology Research Laboratories, Liverpool University, United Kingdom
    J Infect Dis 207:S78-84. 2013
    Increases in the prevalence of resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) have been observed among previously untreated individuals in all areas of sub-Saharan Africa...
  41. ncbi Twenty years of HIV-1 non-nucleoside reverse transcriptase inhibitors: time to reevaluate their toxicity
    A Blas-Garcia
    Departamento de Farmacologia, Facultad de Medicina, Universidad de Valencia, Valencia, Spain
    Curr Med Chem 18:2186-95. 2011
    Twenty years of effective clinical application have consolidated non-nucleoside reverse transcriptase inhibitors (NNRTI) as essential components of the Highly Active Antiretroviral Therapy (HAART) employed in the treatment of Human ..
  42. ncbi Self-Reported adherence to antiretroviral treatment among HIV-infected people in Central China
    Honghong Wang
    School of Nursing, Central South University, Changsha, Hunan, China
    AIDS Patient Care STDS 22:71-80. 2008
    ..Prospective studies are needed to evaluate the efficacy of reminder devices to improve adherence in this population and to describe the prevalence and incidence of ARV resistance...
  43. pmc Selective excision of AZTMP by drug-resistant human immunodeficiency virus reverse transcriptase
    P L Boyer
    ABL Basic Research Program, National Cancer Institute Frederick Cancer Research and Development Center, Frederick, Maryland 21702 1201, USA
    J Virol 75:4832-42. 2001
    ..Steric constraints involving the azido group cause the end of an AZT 5'-monophosphate-terminated primer to preferentially reside at the nucleotide binding site, which favors excision...
  44. ncbi Increased platelet reactivity in HIV-1-infected patients receiving abacavir-containing antiretroviral therapy
    Claudette S Satchell
    HIV Molecular Research Group, School of Medicine and Medical Sciences, University College Dublin, Ireland
    J Infect Dis 204:1202-10. 2011
    ..Given the role of platelet aggregation in thrombus formation in MI and the reversible nature of the abacavir association, we hypothesized that patients treated with abacavir would have increased platelet reactivity...
  45. ncbi Impact of CRF01_AE-specific polymorphic mutations G335D and A371V in the connection subdomain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on susceptibility to nucleoside RT inhibitors
    Junko Tanuma
    AIDS Clinical Center, National Center for Global Health and Medicine, 1 21 1 Toyama, Shinjuku ku, Tokyo 162 8655, Japan
    Microbes Infect 12:1170-7. 2010
    ..H domain of reverse transcriptase (RT) of subtype B HIV-1 contribute to resistance to nucleoside reverse transcriptase inhibitors (NRTIs)...
  46. ncbi The MONET trial: week 144 analysis of the efficacy of darunavir/ritonavir (DRV/r) monotherapy versus DRV/r plus two nucleoside reverse transcriptase inhibitors, for patients with viral load < 50 HIV-1 RNA copies/mL at baseline
    J R Arribas
    University Hospital La Paz, IdiPAZ, Madrid, Spain
    HIV Med 13:398-405. 2012
    ..two nucleoside reverse transcriptase inhibitors (NRTIs) plus DRV/r at the primary 48-week analysis...
  47. pmc Impact of minority nonnucleoside reverse transcriptase inhibitor resistance mutations on resistance genotype after virologic failure
    Jonathan Z Li
    Division of Infectious Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Infect Dis 207:893-7. 2013
    ..NNRTI regimen choice and preexisting NNRTI-resistant minority variants were both associated with the probability and type of resistance mutations detected after virologic failure...
  48. ncbi Declining prevalence of HIV-1 drug resistance in antiretroviral treatment-exposed individuals in Western Europe
    Andrea De Luca
    Catholic University of the Sacred Heart, Rome, Italy
    J Infect Dis 207:1216-20. 2013
    ..5% in 2005, decreasing thereafter. The proportion of cases exhausting available drug options dropped from 32% in 2000 to 1% in 2008. Reduced risk of resistance over calendar years was confirmed by multivariable analysis...
  49. pmc High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen
    Henry Sunpath
    McCord Hospital, Durban, South Africa
    AIDS 26:1679-84. 2012
    ..We sought to determine the rate of the K65R mutation in patients receiving tenofovir (TDF)-based antiretroviral therapy (ART) with subtype C HIV infection...
  50. ncbi Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: a multicentre cohort study
    Raph L Hamers
    PharmAccess Foundation, Department of Global Health, Amsterdam Institute for Global Health and Development, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands
    Lancet Infect Dis 12:307-17. 2012
    ..We studied pretreatment drug resistance and virological, immunological, and drug-resistance treatment outcomes in a large prospective cohort...
  51. pmc Quantifying the impact of nevirapine-based prophylaxis strategies to prevent mother-to-child transmission of HIV-1: a combined pharmacokinetic, pharmacodynamic, and viral dynamic analysis to predict clinical outcomes
    M Frank
    Department of Clinical Pharmacy, Institute of Pharmacy, Martin Luther Universitaet Halle Wittenberg, Wolfgang Langenbeck Str 4, 06120 Halle, Germany
    Antimicrob Agents Chemother 55:5529-40. 2011
    ....
  52. pmc Novel aptamer inhibitors of human immunodeficiency virus reverse transcriptase
    Jeffrey J Destefano
    Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA
    Oligonucleotides 18:133-44. 2008
    ..Phosphothioate nucleotides or the presence of a 3' dideoxy G residue did not alter affinity. The 37-nt aptamer was a potent inhibitor of HIV-RT in vitro and functioned by blocking binding of other primer-templates...
  53. pmc Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors
    Nicolas Sluis-Cremer
    Division of Infectious Diseases, University of Pittsburgh School of Medicine, S817 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Virus Res 134:147-56. 2008
    ..Accordingly, in this review we describe the multiple mechanisms by which NNRTIs inhibit HIV-1 reverse transcription (and in some cases HIV-2 reverse transcription) and other key steps involved in HIV-1/HIV-2 replication...
  54. ncbi Raltegravir and unboosted atazanavir dual therapy in virologically suppressed antiretroviral treatment-experienced HIV patients
    Damien V Cordery
    National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia
    Antivir Ther 15:1035-8. 2010
    ....
  55. ncbi Telomerase inhibition using azidothymidine in the HT-29 colon cancer cell line
    Tommy Brown
    Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Ann Surg Oncol 10:910-5. 2003
    ..We investigated the effects of telomerase inhibition by using the reverse transcriptase inhibitor azidothymidine (AZT) in the human colorectal cancer cell line HT-29 in the presence and absence of 5-fluorouracil (5-FU)...
  56. ncbi Cyclic induction of senescence with intermittent AZT treatment accelerates both apoptosis and telomere loss
    Hyun Jung Ji
    Cancer Metastasis Research Center, Young Cancer Center, Yonsei University College of Medicine, Seoul, Seodaemun Ku, Korea
    Breast Cancer Res Treat 93:227-36. 2005
    ..AZT is also known to inhibit reverse transcriptase, as well as other cellular enzymes including DNA polymerase gamma, thymidine kinase, and telomerase...
  57. pmc Broad-spectrum aptamer inhibitors of HIV reverse transcriptase closely mimic natural substrates
    Mark A Ditzler
    Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA
    Nucleic Acids Res 39:8237-47. 2011
    ..These results inform our perspective on how sustained, broad-spectrum inhibition of RT can be achieved by aptamers...
  58. ncbi Nucleoside reverse transcriptase inhibitor toxicity and mitochondrial DNA
    Christopher A Koczor
    Emory University, Department of Pathology, Atlanta, GA 30322, USA
    Expert Opin Drug Metab Toxicol 6:1493-504. 2010
    HIV/AIDS is a worldwide epidemic. While there remains no cure for the HIV-1 infection, nucleoside reverse transcriptase inhibitors (NRTIs) have helped transform the HIV-1 infection from a lethal disease into a chronic illness...
  59. ncbi The role of HIV and antiretroviral therapy in bone disease
    Felix Gutierrez
    Infectious Diseases Unit, Hospital General Universitario, Elche, Spain
    AIDS Rev 13:109-18. 2011
    ..Given the complex interaction between HIV and drugs in causing low bone mineral density, optimization of antiretroviral therapy and preemptive strategies aimed to prevent bone loss during therapy may be of paramount importance...
  60. ncbi Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study
    Todd Hulgan
    Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA
    AIDS 19:1341-9. 2005
    HIV nucleoside reverse transcriptase inhibitors (NRTI) can cause peripheral neuropathy that is a result of mitochondrial injury. Polymorphisms in the mitochondrial genome define haplogroups that may have functional implications...
  61. ncbi Molecular determinants of multi-nucleoside analogue resistance in HIV-1 reverse transcriptases containing a dipeptide insertion in the fingers subdomain: effect of mutations D67N and T215Y on removal of thymidine nucleotide analogues from blocked DNA prim
    Tania Matamoros
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, 28049 Madrid, Spain
    J Biol Chem 279:24569-77. 2004
    ....
  62. ncbi Relationship between antiretrovirals used as part of a cART regimen and CD4 cell count increases in patients with suppressed viremia
    Amanda Mocroft
    Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK
    AIDS 20:1141-50. 2006
    ..It is unknown if the CD4 cell count response differs according to antiretroviral drugs used in combination antiretroviral therapy (cART) in patients with maximal virological suppression [viral load (VL) < 50 copies/ml]...
  63. 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...
  64. pmc Human immunodeficiency virus types 1 and 2 exhibit comparable sensitivities to Zidovudine and other nucleoside analog inhibitors in vitro
    Robert A Smith
    University of Washington, Department of Pathology, K 046 HSB, Box 357705, 1959 NE Pacific St, Seattle, WA 98195, USA
    Antimicrob Agents Chemother 52:329-32. 2008
    ..These data support the use of nucleoside analogs for antiviral therapy of HIV-2 infection...
  65. pmc Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors
    Nicolas Sluis-Cremer
    Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, S817 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Antimicrob Agents Chemother 51:48-53. 2007
    ..Taken together, these findings indicate that the K70E mutation, like the K65R mutation, reduces susceptibility to NRTI by selectively decreasing NRTI-TP incorporation and is antagonistic to TAM-mediated nucleotide excision...
  66. pmc Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design
    Joseph D Bauman
    Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ, USA
    Nucleic Acids Res 36:5083-92. 2008
    ..The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs...
  67. pmc Efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1
    Michael J Hofman
    Center for Comparative Medicine, University of California, Davis, CA 95616, USA
    Antimicrob Agents Chemother 48:3483-90. 2004
    ..Virus isolated from these two animals contained the K103N and Y188C or Y188L mutations. The RT-SHIV-rhesus macaque model may prove useful for studies of antiretroviral drug combinations that include efavirenz...
  68. 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...
  69. 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...
  70. pmc Efavirenz versus nevirapine-based initial treatment of HIV infection: clinical and virological outcomes in Southern African adults
    Jean B Nachega
    Department of Internal Medicine and Center for Infectious Disease, Stellenbosch University, Cape Town, South Africa
    AIDS 22:2117-25. 2008
    ..To determine the effectiveness of efavirenz versus nevirapine in initial antiretroviral therapy regimens for adults in sub-Saharan Africa...
  71. ncbi Risk of severe hepatotoxicity associated with antiretroviral therapy in the HIV-NAT Cohort, Thailand, 1996-2001
    W Phillip Law
    National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia
    AIDS 17:2191-9. 2003
    ..To examine rates and predictors of severe hepatotoxicity with combination antiretroviral therapy in a developing country setting: the eight HIV-NAT randomized controlled trials in Thailand...
  72. ncbi Effectiveness of antiretroviral therapy among HIV-infected children in sub-Saharan Africa
    Catherine G Sutcliffe
    Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
    Lancet Infect Dis 8:477-89. 2008
    ....
  73. 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...
  74. pmc High-resolution structures of HIV-1 reverse transcriptase/TMC278 complexes: strategic flexibility explains potency against resistance mutations
    Kalyan Das
    Center for Advanced Biotechnology and Medicine and Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
    Proc Natl Acad Sci U S A 105:1466-71. 2008
    ..The crystal structures provide a better understanding of how the flexibility of an inhibitor can compensate for drug-resistance mutations...
  75. ncbi Stability of antiretroviral regimens in patients with viral suppression
    Rebecca K Lodwick
    Research Department of Infection and Population Health, Division of Population Health, Royal Free and University College Medical School, London, UK
    AIDS 22:1039-46. 2008
    ..To study the rate of treatment change due to toxicities in patients who achieved viral suppression within 6 months of starting antiretroviral therapy and who have never experienced virological failure...
  76. pmc Structure of HIV-1 reverse transcriptase with the inhibitor beta-Thujaplicinol bound at the RNase H active site
    Daniel M Himmel
    Center for Advanced Biotechnology and Medicine and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854 8021, USA
    Structure 17:1625-35. 2009
    ..We provide biochemical evidence that beta-thujaplicinol is a slow-binding RNH inhibitor with noncompetitive kinetics and suggest that it forms a tropylium ion that interacts favorably with RT and the RNA:DNA substrate...
  77. ncbi Antiretroviral resistance patterns and factors associated with resistance in adult patients failing NNRTI-based regimens in the Western Cape, South Africa
    Gert U van Zyl
    Division of Medical Virology, Stellenbosch University, Tygerberg, Cape Town, South Africa
    J Med Virol 83:1764-9. 2011
    ..Major protease inhibitor mutations were not detected. A delayed response to ART failure may risk accumulation of TAMs in patients on an NNRTI-based regimen. The use of NVP rather than EFV was associated with ETV resistance...
  78. ncbi Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase
    Tanya Welz
    Department of HIV Genitourinary Medicine, King s College Hospital, London, UK
    AIDS 24:1923-8. 2010
    ....
  79. 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...
  80. ncbi Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana: a randomized trial: the Mashi Study
    Ibou Thior
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Mass 02115, USA
    JAMA 296:794-805. 2006
    ..Postnatal transmission of human immunodeficiency virus-1 (HIV) via breastfeeding reverses gains achieved by perinatal antiretroviral interventions...
  81. pmc Novel bimodular DNA aptamers with guanosine quadruplexes inhibit phylogenetically diverse HIV-1 reverse transcriptases
    Daniel Michalowski
    Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65211, USA
    Nucleic Acids Res 36:7124-35. 2008
    ..The bimodular ssDNA aptamers inhibited RT from diverse primate lentiviruses with low nM IC(50) values. These data provide insight into the requirements for broad-spectrum RT inhibition by nucleic acid aptamers...
  82. ncbi Clearance of the original hepatitis B virus YMDD-motif mutants with emergence of distinct lamivudine-resistant mutants during prolonged lamivudine therapy
    C T Yeh
    Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan
    Hepatology 31:1318-26. 2000
    ..These results suggested that distinct lamivudine-resistant mutants could emerge and replace the original YMDD-motif mutants as the cause of continuing chronic hepatitis during prolonged lamivudine therapy...
  83. ncbi Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study
    Todd T Brown
    Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA
    AIDS 19:1375-83. 2005
    ..To estimate insulin resistance and its relationship to antiretroviral therapy (ART) in a cohort of HIV-infected persons with comparison to HIV-seronegative controls...
  84. pmc Population pharmacokinetics of tenofovir in human immunodeficiency virus-infected patients taking highly active antiretroviral therapy
    Vincent Jullien
    Service de Pharmacologie Clinique, Hopital Cochin Saint Vincent de Paul, 74 82 Avenue Denfert Rochereau, 75674 Paris Cedex 14, France
    Antimicrob Agents Chemother 49:3361-6. 2005
    ..In patients without tubular dysfunction, AUC(0-24) values markedly decreased from 6.7 to 1.4 mg . h/liter for BW/S(CR) increasing from 0.44 to 1.73. The relevance of a dosage adjustment based on BW/S(CR) should be further evaluated...
  85. pmc Progressive mitochondrial compromise in brains and livers of primates exposed in utero to nucleoside reverse transcriptase inhibitors (NRTIs)
    Rao L Divi
    Carcinogen DNA Interactions Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    Toxicol Sci 118:191-201. 2010
    ..4-56.5% in liver. These investigations suggest that some NRTI-exposed human infants may sustain similar mitochondrial compromise in brain and liver and should be followed long term for cognitive integrity and liver function...
  86. ncbi Highly active antiretroviral treatment against STLV-1 infection combining reverse transcriptase and HDAC inhibitors
    Philippe V Afonso
    Unité d Epidémiologie et Physiopathologie des Virus Oncogènes, Centre National de la Recherche Scientifique CNRS URA 3015, Institut Pasteur, Paris, France
    Blood 116:3802-8. 2010
    ..Such treatments may be useful to reduce the risk of HAM/TSP in asymptomatic carriers with a high PVL...
  87. pmc Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance
    Kalyan Das
    Center for Advanced Biotechnology and Medicine CABM, Rutgers University, Piscataway, New Jersey 08854, USA
    J Biol Chem 284:35092-100. 2009
    ..These K65R-mediated effects on RT structure and function help us to visualize the complex interaction with other key nucleotide RT drug resistance mutations, such as M184V, L74V, and thymidine analog resistance mutations...
  88. 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
    ..treatment with a combination of three antiretroviral drugs consisting of two nucleoside analogue reverse transcriptase inhibitors and a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor...
  89. pmc Suppression of viremia and evolution of human immunodeficiency virus type 1 drug resistance in a macaque model for antiretroviral therapy
    Zandrea Ambrose
    HIV Drug Resistance Program, National Cancer Institute, Building 535, Room 123, Frederick, MD 21702, USA
    J Virol 81:12145-55. 2007
    ..By contrast, ART effectively suppressed RT-SHIV in 5/6 animals. These data indicate that suboptimal therapy facilitates HIV-1 drug resistance and suggest that this model can be used to investigate persisting viral reservoirs...
  90. ncbi Carrageenan/MIV-150 (PC-815), a combination microbicide
    Jose A Fernández-Romero
    Population Council, New York, NY, USA
    Sex Transm Dis 34:9-14. 2007
    ....
  91. ncbi Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics
    Brian P Kearney
    Department of Pharmacology and Pharmacokinetics, Gilead Sciences, Inc, Foster City, California 94404, USA
    Clin Pharmacokinet 43:595-612. 2004
    ..No dosage adjustment of tenofovir DF is necessary in patients with liver disease...
  92. ncbi The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes
    David A van de Vijver
    Eijkman Winkler Institute, Department of Virology, University Medical Center Utrecht, G04 614, 3584 CX Utrecht, The Netherlands
    J Acquir Immune Defic Syndr 41:352-60. 2006
    ..This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (>600 of non-B subtype) isolated from anti-retroviral-naive patients in Europe...
  93. ncbi Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients
    Claudine Duvivier
    AP HP, Groupe Hospitalier Pitie Salpetriere, Service de Maladies Infectieuses et Tropicales, Paris, France
    AIDS 23:817-24. 2009
    ..To evaluate the change in bone mineral density (BMD) at specific sites in patients initiating antiretroviral therapy in a substudy of the ANRS 121 trial...
  94. 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...
  95. pmc Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission
    Francois Dabis
    Unité INSERM 593, Institut de Santé Publique, Epidémiologie et Développement ISPED, Universite Victor Segalen, 146 rue Leo Saignat, 33076 Bordeaux, France
    AIDS 19:309-18. 2005
    ..We evaluated the 6-week field efficacy of two more PMTCT drug combinations...
  96. pmc A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo
    Martin Markowitz
    Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York 10016, USA
    J Virol 77:5037-8. 2003
    ..7 day, and the generation time of HIV-1 in vivo, approximately 2 days, confirming the dynamic nature of HIV-1 replication...
  97. ncbi HLA-B*5701 screening for hypersensitivity to abacavir
    Simon Mallal
    Royal Perth Hospital and Murdoch University, Perth, Australia
    N Engl J Med 358:568-79. 2008
    ..This study was designed to establish the effectiveness of prospective HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir...
  98. pmc Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3'-azido-3'-dideoxythymidine
    Jessica H Brehm
    University of Pittsburgh School of Medicine, S818 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    J Virol 81:7852-9. 2007
    ....
  99. ncbi Differential incorporation and removal of antiviral deoxynucleotides by human DNA polymerase gamma
    S E Lim
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 276:23616-23. 2001
    ..Thus, although their greatest inhibitory effects are through incorporation and chain termination, persistence of these analogs in DNA and inhibition of exonucleolytic proofreading may also contribute to mitochondrial toxicity...
  100. pmc Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration
    Caroline A Sabin
    Lancet 371:1417-26. 2008
    Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infarction in HIV-infected individuals is unclear...

Research Grants64

  1. AIDS Neurotherapeutics and BBB Drug Efflux
    William Pardridge; Fiscal Year: 2007
    ..inhibitors) or non-p-glycoprotein BBB active efflux transporters (AET) [in the case of the nucleoside reverse transcriptase inhibitors (NRTIs)]...
  2. A Targeted Preemptive Approach to Addressing Mitochondrial Toxicity of Nucleoside
    John K Buolamwini; Fiscal Year: 2013
    ..virus (HIV) revolutionized acquired immunodeficiency disease (AIDS) therapy, nucleoside reverse transcriptase inhibitors (NRTIs) that are a cornerstone of HAART cocktails have been found to cause severe mitochondrial ..
  3. Alcohol &Antiretrovirals in HIV Infection, Oxidative Stress and Liver Disease
    Marianna K Baum; Fiscal Year: 2012
    ..Nucleoside reverse transcriptase inhibitors (NRTI) in combination with non-NRTIs and protease inhibitors have demonstrated their effectiveness as ..
  4. Drug Transport at the Blood-Testis Barrier
    Nathan J Cherrington; Fiscal Year: 2013
    ..Indeed, protease inhibitors and non-nucleoside reverse transcriptase inhibitors are actively excluded at the BTB and do not reach therapeutic concentrations in the testis...
  5. Kinetics of DNA polymerase gamma upon mutation and nucleoside analog exposure
    CHRISTAL DYANE SOHL; Fiscal Year: 2013
    ..For patients infected with HIV, nucleoside reverse transcriptase inhibitors (NRTIs) are a critical component of treatment, but unfortunately DNA pol 3 also can use these ..
  6. Metabolism and toxicity of NRTIs in non-replicating tissues
    Edward E McKee; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Nucleoside reverse transcriptase inhibitors (NRTIs) are an important component of long-term AIDS therapy and are associated with a host of mild to lethal side effects that are caused by mitochondrial ..
  7. Global HIV Drug Therapies and Mitochondrial Complications and Mechanisms
    Mariana Gerschenson; Fiscal Year: 2012
    ..toxicities due to mitochondrial (mt) dysfunction are common complications seen with the nucleoside reverse transcriptase inhibitors (NRTIs)...
  8. CNS Delivery of Activated Antiviral Drugs with Reduced Neurotoxicity (Nano-NRTIs)
    Serguei V Vinogradov; Fiscal Year: 2013
    ..The important components of HAART, nucleoside reverse transcriptase inhibitors (NRTI), induce neurotoxicity due to the degradation of mitochondrial functions in peripheral and CNS ..
  9. Impact of TB on Outcome of HIV in Pregnant Women
    Richard E Chaisson; Fiscal Year: 2013
    ..has the potential to interfere with the efficacy of treatment to prevent MTCT with the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine and efavirenz because of upregulation of P450 cytochromes by rifampin, the key ..
  10. HIV Nucleoside Analogs Translational Studies: Resistance and Metabolism
    Elijah Paintsil; Fiscal Year: 2012
    ..virology and pharmacology by the integration of research studies on the cellular pharmacology of HIV reverse transcriptase inhibitors in relation to toxicity in different individuals with the aim of optimizing HIV therapeutic regimens ..
  11. Stellenbosch University Clinical Trial Unit, Cape Town, South Africa
    MARK FREDRIC COTTON; Fiscal Year: 2013
    ..record of conducting ARV trials for industry and initiating a trial comparing two non-nucleoside reverse transcriptase inhibitors as a third component of ARV therapy...
  12. ULTRAFAST PROCESSES IN PROTEINS AND OTHER ASSEMBLIES
    Feng Gai; Fiscal Year: 2013
    ..time through associated water in transmembrane (TM) helices, proton channels, fast folding proteins, reverse transcriptase inhibitors and fibrils will be obtained by two dimensional infrared spectroscopy (2D IR) a powerful new method...
  13. Risk Factors for the Development of Lactic Acidosis and Pancreatitis Among HAART-
    William Wester; Fiscal Year: 2011
    ..Nucleoside analogue reverse transcriptase inhibitors (NRTIs) are effective antiretroviral therapies for the treatment of HIV-1 infected adults and they ..
  14. Alternative Formulations of Tenofovir and UC781
    Lisa C Rohan; Fiscal Year: 2013
    ..The reverse transcriptase inhibitors tenofovir (TFV) and UC781 have significant activity against HIV...
  15. LIPOGENESIS & LIPOPROTEIN COMPLICATIONS OF HIV THERAPY
    David Y Hui; Fiscal Year: 2010
    ..In contrast, treatment that includes non-nucleoside reverse transcriptase inhibitors (NNRTI) nevirapine and efavirenz increases HDL-cholesterol...
  16. Innovative methods for measuring antiretroviral exposure
    RUTH MARTHA GREENBLATT; Fiscal Year: 2010
    ..develop methods for quantifying the amount of antiretroviral protease inhibitors and non-nucleoside reverse transcriptase inhibitors in small samples of hair...
  17. Discovery of Novel HIV-1 Reverse Transcriptase Inhibitors by Fragment Screening
    ANGELA MCKOY; Fiscal Year: 2013
    ..The fragment screening approach allows for efficient search of chemical space and should lead to the identification of novel scaffolds for inhibiting HIV-1 RNH activity at both the active site and allosteric pockets. ..
  18. HIV and NRTI's-induced painful pathogenic mechanisms and gene therapy
    Shuanglin Hao; Fiscal Year: 2013
    ..created by application of gp120 to the sciatic nerve along with systemic administration of nucleoside reverse transcriptase inhibitors (NRTIs), have allowed studies of the pathogenesis of HIV/HAART neuropathic pain...
  19. Treatment Options for Protease Inhibitor Exposed Children
    Louise Kuhn; Fiscal Year: 2013
    ....
  20. Analysis of HIV-1 Uncoating
    AMY ELIZABETH HULME; Fiscal Year: 2013
    ..facilitates initiation or progression of uncoating by studying p24CA mutants and the effect of reverse transcriptase inhibitors on uncoating...
  21. Drug-resistance testing in Kenya to improve ART suppression of HIV replication
    Lisa M Frenkel; Fiscal Year: 2013
    ..to their infants, and (3) to maintaining the effectiveness of the current 1st-line non-nucleoside reverse transcriptase inhibitors (NNRTI)- based ART...
  22. HIV-1 evolution in the female genital tract and trafficking to the blood
    Lisa M Frenkel; Fiscal Year: 2013
    ..from production of virions without full- cycles of replication, as nucleoside- and non-nucleoside reverse transcriptase inhibitors (NRTI and NNRTI) would prevent infection of additional cells...
  23. Pharmacogenetics and Drug-Drug Interactions during HIV/TB Therapy
    AWEWURA JACOB KWARA; Fiscal Year: 2011
    ..that rifampin-containing anti-TB therapy reduces the intracellular concentrations of nucleoside reverse transcriptase inhibitors. Successful completion of the proposed studies will generate fundamental knowledge regarding drug-..
  24. Rational Design of NRTI for Drug Resistant HIV-1
    John W Mellors; Fiscal Year: 2010
    Nucleoside analog reverse transcriptase inhibitors (NRTI) are integral components of therapy for HIV-1 infection...
  25. Effects of HIV and ARV Exposure on Child Health and Neurodevelopment in Botswana.
    Shahin Lockman; Fiscal Year: 2013
    ..outcomes following in utero exposure to 3-drug HAART that contains 2 or more nucleoside reverse transcriptase inhibitors (NRTIs), vs...
  26. Biochemical Pharmacology of Anti-HIV Compounds
    Yung Chi Cheng; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Nucleoside analog reverse transcriptase inhibitors (NRTIs) were the first therapeutic agents to demonstrate clinical efficacy for HIV-1 infection, and continue to be the cornerstone of highly active ..
  27. Origin of Seminal Virus in Human Immunodeficiency Virus Infection
    Martin D Hill; Fiscal Year: 2012
    ..Protease inhibitors and non-nucleoside reverse transcriptase inhibitors appear in semen at a fraction (typically, 2 - 15%) of their concentration in blood...
  28. Studies of toxicities of HIV RT inhibitors to human mitochondrial DNA polymerase
    YUHUI WHITNEY YIN; Fiscal Year: 2012
    ..However, nucleoside reverse transcriptase inhibitors (NRTIs), the indispensable component of the treatment, have displayed severe adverse reaction mostly ..
  29. Plasma and Genital HIV Dynamics in Women
    Michael N Neely; Fiscal Year: 2010
    ..to antiretroviral therapy by women, adolescents, and children, as well as finding that non-nucleoside reverse transcriptase inhibitors (NNRTIs) may be more associated with shedding of HIV RNA from the cervix than are protease inhibitors ..
  30. ANTIRETROVIRAL THERAPIES AND SUBSTANCE ABUSE
    David Greenblatt; Fiscal Year: 2002
    ..antiretroviral therapies (HAART), including the HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), constitute major advances in the treatment of HIV infecffon, but greatly complicate the ..
  31. Nucleoside Transporters In HAART Mitochondrial Toxicity
    John Buolamwini; Fiscal Year: 2006
    ..long-term use of HAART, which is a combination therapy that almost invariably contains nucleoside HIV reverse transcriptase inhibitors (NRTIs), is associated with major toxicities including liver damage, neuoropathy, pancreatitis, ..
  32. Reverse Transcriptase Activity in Megakaryocytes and Platelets
    ANDREW SCOTT WEYRICH; Fiscal Year: 2010
    ..Studies in aim 2 will also provide important clinical information, especially in regards to HIV-infected patients who are medicated with reverse transcriptase inhibitors and patients who receive platelet transfusions.
  33. DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS
    Arun K Ghosh; Fiscal Year: 2010
    ..of HIV-1 protease inhibitors (PIs) in 1996 into combination therapy regimens with two or more reverse transcriptase inhibitors has been critical to the reduction of AIDS related mortality, improvement of quality of life, and ..
  34. Persistent HIV-1 Replication in the Respiratory Tract Despite ART
    Thor Andrew Wagner; Fiscal Year: 2012
    ..gauged in sputum specimens from adults who are or are not treated with tenofovir and non-nucleoside reverse transcriptase inhibitors, which appear to be more active in macrophages...
  35. Antiretroviral Therapy for HIV-2 Infection in Senegal
    GEOFFREY SCOTT GOTTLIEB; Fiscal Year: 2013
    ..Because HIV-2 is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors and may have partial resistance to some protease inhibitors (PI), treating HIV-2 and HIV-1/HIV-2 dual ..
  36. Cellular pharmacology of tenofovir and emtricitabine for HIV prophylaxis
    PETER LINDSAY ANDERSON; Fiscal Year: 2012
    ..TFV and FTC belong to the nucleoside analog reverse transcriptase inhibitors (NRTls) drug class, which undergoes sequential phosphorylation in patients to the intracellular ..
  37. Novel Mechanisms for Coreceptor Switching
    Donald E Mosier; Fiscal Year: 2013
    ..Prior antiviral therapy with reverse transcriptase inhibitors may lead to a higher mutation rate that differently impacts R5 viruses...
  38. Ultrapotent Inhibitors of Wild-type and Multi-drug Resistant HIV
    Stefan Sarafianos; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Nucleoside reverse transcriptase inhibitors (NRTIs) are among the most potent antiretrovirals used clinically, and are often used in first-line therapy for HIV infection...
  39. NUCLEOSIDES WITH DUAL ANTI-HIV AND HBV ACTIVITY
    RAYMOND SCHINAZI; Fiscal Year: 2009
    ..and preclinical antiretroviral agents nucleoside analogs, and various protease and non-nucleoside reverse transcriptase inhibitors. It was effective against cloned viruses with single and multiple mutations in the reverse ..
  40. TDM & Drug Interactions in HIVinfected Substance Abusers
    Gene Morse; Fiscal Year: 2007
    ..to the rapid assessment of complex drug interactions between protease inhibitors and nonnucleoside reverse transcriptase inhibitors (NNRTIs), and commonly prescribed medications including methadone, ethinyl estradiol, fluconazole, ..
  41. Optimizing NNRTI Doses in Patients with HIV and TB
    Terrence Blaschke; Fiscal Year: 2007
    ..Services recommends the use of rifampin (RMP) with a regimen consisting of one of the non nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) or nevirapine (NVP) plus 2 nucleoside reverse transcriptase inhibitors (NRTI),..
  42. Synthesis of New NNRTLs for the Treatment of AIDS
    Mark Cushman; Fiscal Year: 2005
    A current need exists for novel non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) that: 1) have lower toxicities than the existing NNRTIs, 2) have unique resistance mutation profiles and remain active against mutant reverse ..
  43. ORAL BIOAVAILABILITY AND VARIABILITY OF ANTIAIDS DRUGS
    Patrick Sinko; Fiscal Year: 2000
    ..specific drugs to be studied include HIV protease inhibitors (saquinavir, ritonavir), non-nucleoside reverse transcriptase inhibitors (delaviridine, UC-781), and antiherpetic/anti-CMV agents (valacyclovir, lobucavir)...
  44. Desaturases and Acetylenases from Basidiomycete Fungi
    ROBERT MINTO; Fiscal Year: 2004
    ..Through the above studies, we will test the hypothesis that multiple FAD2-like enzymes are required for polyacetylene biosynthesis, while characterizing an understudied group of important fungal enzymes. ..
  45. HAART Regimens in Substance Abusers
    David Greenblatt; Fiscal Year: 2003
    ..antiretroviral therapies (HAART), including the HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), has prolonged survival and improved quality of life for individuals with HIV infection and ..
  46. HIV/AIDS Intravirion Reverse Transcription and Virucides
    Hui Zhang; Fiscal Year: 2007
    ..We have also demonstrated that triphosphorylated derivatives of nucleoside-analogue reverse transcriptase inhibitors (NRTIs) and non-nucleoside-analogue RT inhibitors (NNRTIs) can directly enter lentivirions via pores ..
  47. SYNTHESIS AND BIOTRANSFORMATION OF ANTIHIV PRODRUGS
    David Chu; Fiscal Year: 2000
    ..The first issue is the viral reservoir. Triple combination therapy (two nucleoside reverse transcriptase inhibitors plus one protease inhibitor) can virtually eliminate the HIV viral load to undetectable level in the ..
  48. Mutagenesis of Single/Combined NRTI Drugs in Human Cells
    Vernon Walker; Fiscal Year: 2004
    ..in pregnant women poses a risk for neoplasia in the infants exposed in utero to nucleoside analogue reverse transcriptase inhibitors (NRTIs)...
  49. Mitochondria And Metabolic Complications Of HIV
    Pablo Tebas; Fiscal Year: 2006
    ..Clinical evidence suggests that specific nucleoside analogue reverse transcriptase inhibitors (particularly d4T and AZT) are associated with peripheral adipose tissue wasting, which may result ..
  50. Nanodelivery of active NRTI to the central nervous system: humanized HIV murine m
    Serguei Vinogradov; Fiscal Year: 2009
    ..Nucleoside analogs (NA), aka reverse transcriptase inhibitors (NRTIs), are cornerstones of the HAART...
  51. HIV-1 Envelope phenotype/genotype database resources
    Colombe Chappey; Fiscal Year: 2006
    ..As with protease and reverse transcriptase inhibitors, both the development and use of entry inhibitors will benefit from the comprehensive appreciation of ..
  52. COMBINATION GENETIC-CHEMOTHERAPEUTIC HIV1 THERAPY
    ROGER INOUYE; Fiscal Year: 2002
    ..Anti-Rev system genetic elements will be used in concert with chemotherapeutic reverse transcriptase inhibitors to assess changes in vitro anti-viral activity relative to standard chemotherapy...
  53. 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...
  54. HIV Protease Inhibitors & Glucose Transport
    Mike Mueckler; Fiscal Year: 2007
    ..Combined treatment of HIV-infected patients with reverse transcriptase inhibitors and PIs (Highly Active Antiretroviral Therapy, HAART) has been shown to delay the onset of overt ..
  55. ASYMMETRIC 1,2-ADDITIONS
    DAVID COLLUM; Fiscal Year: 2005
    ..of chiral amino alkoxides (R*OLi) employed as the critical steps in syntheses of non-nucleosides HIV reverse transcriptase inhibitors. The work will be carried out in collaboration with Dupont Pharmaceuticals and ASI Applied Systems...
  56. Synthesis of Nucleoside Analogs as HIV-1 Reverse Transcriptase Inhibitors
    KIMBERLYNN DAVIS; Fiscal Year: 2007
    ..Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs to be used clinically for the treatment of HIV and remain an essential ..
  57. NRTI-induced Mitochondrial Cardiomyopathy
    Kendall Wallace; Fiscal Year: 2006
    ..The cornerstone of the HAART drug regimen for treating HIV are nucleoside analog reverse transcriptase inhibitors (NRTIs), which inhibit viral RNA-dependent DNA polymerases...
  58. Chain Terminator Excision in HIV -1 Drug Resistance
    MICHAEL PARNIAK; Fiscal Year: 2006
    DESCRIPTION (provided by applicant): HIV-1 resistance to nucleoside reverse transcriptase inhibitors (NRTI) involves discrimination (selective alterations of RT binding of NRTI-triphosphate compared to the analogous dNTP), and chain ..
  59. STRATEGIC MANAGEMENT OF ANTIRETROVIRALS IN HIV INFECTION
    Pablo Tebas; Fiscal Year: 2001
    ..The availability of protease inhibitors and non-nucleoside reverse transcriptase inhibitors allowed the development of combinations of antiretroviral drugs (HAART) that can completely block HIV ..
  60. Mitochondrial Nucleotide Carriers of NRTI Metabolites
    Tod Gulick; Fiscal Year: 2007
    DESCRIPTION (provided by applicant): Nucleoside reverse transcriptase inhibitors (NRTI) are critical components of highly active anti-viral therapies...
  61. IMMUNIZING BY MUCOSAL SIV EXPOSURE DURING RT INHIBITION
    Lisa Frenkel; Fiscal Year: 1999
    ..The administration of reverse transcriptase inhibitors could provide prophylaxis from chronic infection while allowing an modicum of infection which ..
  62. Simulating Mitochondrial Toxicity of Nucleoside Analogs
    David Samuels; Fiscal Year: 2007
    ..Highly active antiretroviral therapy (HAART) typically contains two or more nucleoside reverse transcriptase inhibitors (NRTIs)...
  63. NMR STUDIES OF THE HIV ENVELOPE PROTEINS
    Michael Caffrey; Fiscal Year: 2004
    ..prophylactic properties, as well as being alternative and complementary therapies to the protease and reverse transcriptase inhibitors currently employed...
  64. Rationally Designed NNRTI Agents
    Taracad Venkatachalam; Fiscal Year: 2002
    We designed several reverse transcriptase inhibitors (RT) using our novel model of the non-nucleoside inhibitor binding pocket of HIV RT which combines high resolution crystal structure information from 9 NNRTI-RT complexes...