All Journals > The Journal of Infectious Diseases > 1 December 2005 > Tenofovir, Abacavir, and Lamivudine

Article Tools

Search for Related Articles

  • By Author
  • Search In

Announcements

Science Watch logo

JID Article Named "New Hot Paper" by ScienceWatch.com

Dr. Lauri Hicks' 2007 article on pneumococcal disease has been named a "hot new paper" by Thompson Reuters' ScienceWatch.com. Read a Q&A about the article with Dr. Hicks here. 

Press Release

Unique Collaboration Charts the Migrations of a Parasite that Affected History
Researchers Sequence Louse DNA from Mummies and Propose New Model for its Development


In the News

Featured in Grist
"Another symptom of swine flu: instant amnesia" May 11, 2009
Swine Influenza Virus: Zoonotic Potential and Vaccination Strategies for the Control of Avian and Swine Influenzas
Eileen Thacker and Bruce Janke
Read the veterinary literature on swine flu and you get a strong sense of what might be called vaccination treadmill: the hog industry is literally scrambling to generate new vaccines for the rapidly evolving flu strains that sweep through CAFOs. Writing in the Journal of Infectious Diseases [PDF] in 2008, Eileen Thacker and Bruce Janke of Iowa State University paint a stark picture: “A number of genetically diverse viruses are circulating in swine herds throughout the world and are a major cause of concern to the swine industry,” they write. “Influenza virus infections in swine and poultry are potential sources of viruses for the next pandemic among humans.”

Featured in New York Times
"Fear of a Swine Flu Epidemic in 1976 Offers Some Lessons, and Concerns, Today" May 8, 2009
Anti‐Ganglioside Antibody Induction by Swine (A/NJ/1976/H1N1) and Other Influenza Vaccines: Insights into Vaccine‐Associated Guillain‐Barré Syndrome
Irving Nachamkin, Sean V. Shadomy, Anthony P. Moran, Nancy Cox, Collette Fitzgerald, Huong Ung, Adrian T. Corcoran, John K. Iskander, Lawrence B. Schonberger, and Robert T. Chen
Irving Nachamkin, a professor of pathology and laboratory medicine at the University of Pennsylvania, examined some 1976 vaccine that had been saved by a scientist in Texas. In a paper published last year in The Journal of Infectious Diseases, he and colleagues reported that mice given the vaccine made antibodies that reacted with gangliosides, which are components of nerve cells. An antibody attack on gangliosides is part of the disease mechanism of Guillain-Barré.

Featured in AFP
"Swine flu vaccine 'could be ready soon'" May 7, 2009
A Broadly Protective Vaccine against Globally Dispersed Clade 1 and Clade 2 H5N1 Influenza Viruses
Mary A. Hoelscher, Neetu Singh, Sanjay Garg, Lakshmi Jayashankar, Vic Veguilla, Aseem Pandey, Yumi Matsuoka, Jacqueline M. Katz, Ruben Donis, Suresh K. Mittal, and Suryaprakash Sambhara
The vaccine Mittal created for the bird flu worked on three different strains isolated over a seven-year period and was described in papers for the Journal of Infectious Diseases and the journal Clinical Pharmacology and Therapeutics.

Featured in Newsweek
"The Path of a Pandemic" http://www.newsweek.com/id/195692
Swine Influenza Virus: Zoonotic Potential and Vaccination Strategies for the Control of Avian and Swine Influenzas
Eileen Thacker and Bruce Janke
Last year researchers from Iowa State University in Ames warned that pigs located in industrial-scale farms were being subjected to influenza infections from farm poultry, wild birds and their human handlers. Writing in The Journal of Infectious Diseases, Eileen Thacker and Bruce Janke said, "As a result of the constantly changing genetic makeup of individual influenza viruses in pigs, the U.S. swine industry is continually scrambling to respond to the influenza viruses circulating within individual production systems."

1 December 2005

Volume 192, Number 11
The Journal of Infectious Diseases 2005;192:1921–1930
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19211-0010$15.00
DOI: 10.1086/498069
MAJOR ARTICLE

Early Virologic Nonresponse to Tenofovir, Abacavir, and Lamivudine in HIV‐Infected Antiretroviral‐Naive Subjects

Joel E. Gallant,1

Allan E. Rodriguez,2

Winkler G. Weinberg,3

Benjamin Young,4

Daniel S. Berger,5

Michael L. Lim,6

Qiming Liao,6

Lisa Ross,6

Judy Johnson,6 and

Mark S. Shaefer,6

for the ESS30009 Studya

1Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland; 2University of Miami, Miami, Florida; 3Kaiser Permanente, Atlanta, Georgia; 4Rose Medical Center, Denver, Colorado; 5Northstar Medical Center, Chicago, Illinois; 6GlaxoSmithKline, Research Triangle Park, North Carolina

Background.Antiretroviral combinations that reduce the number of pills and dosing frequency have the potential to simplify therapy. We compared 2 regimens dosed as 2 pills once daily.

Methods.This was a randomized, open‐label, multicenter study of tenofovir disoproxil fumarate versus efavirenz, both administered once daily with the abacavir/lamivudine fixed‐dose combination in treatment‐naive human immunodeficiency virus type 1 (HIV‐1)–infected subjects. After reports of early nonresponse, an unplanned interim analysis was performed. Virologic nonresponse was defined as (1) a <2.0‐log10 copies/mL decrease in HIV‐1 RNA level by week 8, (2) an HIV‐1 RNA rebound of 1.0 log10 copies/mL above the nadir, or (3) for subjects with 2 consecutive HIV‐1 RNA measurements <50 copies/mL, a subsequent increase to >400 copies/mL on 2 consecutive occasions.

Results.We randomized 340 subjects. Median baseline HIV‐1 RNA level and CD4+ cell count were 4.7 log10 copies/mL and 251 cells/mm3, respectively; 194 subjects with HIV‐1 RNA data from 8 weeks were included in the interim analysis. Virologic nonresponse occurred in 50 (49%) of 102 subjects in the tenofovir disoproxil fumarate arm, compared with 5 (5%) of 92 of subjects in the efavirenz arm ( ). Within 12 weeks, viral genotypes for nonresponders in the tenofovir disoproxil fumarate arm showed M184V or I/M/V mixtures in 40 (98%) of 41 subjects and K65R and M184V or mixtures in 22 (54%) of 41 subjects. The protocol was immediately amended to modify the tenofovir disoproxil fumarate arm. The efavirenz arm continued unchanged; after 48 weeks, 120 (71%) of 169 subjects achieved HIV‐1 RNA levels <50 copies/mL.

Conclusion.The tenofovir disoproxil fumarate/abacavir/lamivudine regimen resulted in an unexpected and unacceptably high rate of nonresponse and incidence of K65R and M184V/I. This 3‐drug regimen should not be used.

Received 28 March 2005; accepted 16 June 2005; electronically published 25 October 2005.

  • (See the editorial commentary by Kuritzkes, on pages 1867–8.)

Reprints or correspondence: Dr. Joel E. Gallant, Div. of Infectious Diseases, Johns Hopkins University School of Medicine, 1830 E. Monument St., Rm. 443, Baltimore, MD 21287 ().

Cited by

M. Y. Chowers, B. S. Gottesman, L. Leibovici, U. Pielmeier, S. Andreassen, M. Paul. (2009) Reporting of adverse events in randomized controlled trials of highly active antiretroviral therapy: systematic review. Journal of Antimicrobial Chemotherapy 64:2, 239-250
Online publication date: 1-Sep-2009.
CrossRef
M. Perez-Olmeda, J. Garcia-Perez, E. Mateos, S. Spijkers, M.C. Ayerbe, A. Carcas, J. Alcami. (2009) In vitro analysis of synergism and antagonism of different nucleoside/nucleotide analogue combinations on the inhibition of human immunodeficiency virus type 1 replication. Journal of Medical Virology 81:2, 211-216
Online publication date: 1-Mar-2009.
CrossRef
Albert ML Anderson, Jeffrey L Lennox. (2009) Abacavir/lamivudine fixed dose combination in the treatment of patients with HIV infection. HIV Therapy 3:1, 19-29
Online publication date: 1-Feb-2009.
CrossRef
Karin J. Metzner, Stefano G. Giulieri, Stefanie A. Knoepfel, Pia Rauch, Philippe Burgisser, Sabine Yerly, Huldrych F. Günthard, and Matthias Cavassini. (2009) Minority Quasispecies of Drug‐Resistant HIV‐1 That Lead to Early Therapy Failure in Treatment‐Naive and ‐Adherent Patients. Clinical Infectious Diseases 48:2, 239-247
Online publication date: 15-Jan-2009.
Abstract-Full Text-PDF Version (385 kB)
Mark R. Underwood, Lisa L. Ross, David M. Irlbeck, Peter Gerondelis, Elizabeth Rouse, Marty H. St. Clair, Lan Trinh, Neil Parkin, and E. Randall Lanier. (2009) Sensitivity of Phenotypic Susceptibility Analyses for Nonthymidine Nucleoside Analogues Conferred by K65R or M184V in Mixtures with Wild‐Type HIV‐1. The Journal of Infectious Diseases 199:1, 84-88
Online publication date: 1-Jan-2009.
Abstract-Full Text-PDF Version (270 kB)
Kirk M Chan-Tack, Kimberly A Struble, Nathalie Morgensztejn, Jeffrey S Murray, Roy Gulick, Ben Cheng, Ian Weller, Veronica Miller. (2008) HIV clinical trial design for antiretroviral development: moving forward. AIDS 22:18, 2419-2427
Online publication date: 1-Dec-2008.
CrossRef
Noel A. Gomes, Ashutosh M. Pudage, Santosh S. Joshi, Vikas V. Vaidya, Sagar A. Parekh. (2008) LC–MS–MS Method for Simultaneous Analysis of Abacavir and Lamivudine in Human Plasma, and Its Application to a Bioequivalence Study. Chromatographia 68:7-8, 541-550
Online publication date: 1-Nov-2008.
CrossRef
P. L. Anderson, T. King, J.-H. Zheng, S. MaWhinney. (2008) Cytokine and sex hormone effects on zidovudine- and lamivudine-triphosphate concentrations in vitro. Journal of Antimicrobial Chemotherapy 62:4, 738-745
Online publication date: 27-Jul-2008.
CrossRef
Carmen de Mendoza, Inmaculada Jiménez‐Nacher, Carolina Garrido, Pablo Barreiro, Eva Poveda, Angélica Corral, Natalia Zahonero, Juan González‐Lahoz, and Vincent Soriano. (2008) Changing Patterns in HIV Reverse Transcriptase Resistance Mutations after Availability of Tenofovir. Clinical Infectious Diseases 46:11, 1782-1785
Online publication date: 1-Jun-2008.
Abstract-Full Text-PDF Version (337 kB)
Christoph Stephan. (2008) Experience with tenofovir disoproxil fumarate for antiretroviral therapy. Expert Opinion on Pharmacotherapy 9:7, 1197-1209
Online publication date: 1-Jun-2008.
CrossRef
Viktor von Wyl, Sabine Yerly, Jürg Böni, Philippe Bürgisser, Thomas Klimkait, Manuel Battegay, Enos Bernasconi, Matthias Cavassini, Hansjakob Furrer, Bernard Hirschel, Pietro L. Vernazza, Martin Rickenbach, Bruno Ledergerber, Huldrych F. Günthard, and the Swiss HIV Cohort Study. (2008) Factors Associated with the Emergence of K65R in Patients with HIV‐1 Infection Treated with Combination Antiretroviral Therapy Containing Tenofovir. Clinical Infectious Diseases 46:8, 1299-1309
Online publication date: 15-Apr-2008.
Abstract-Full Text-PDF Version (382 kB)
Calvin J Cohen, Marshall Kubota, Philip S Brachman, William B Harley, Stefan Schneider, Vanessa C Williams, Denise H Sutherland-Phillips, Michael L Lim, Rukmini B Balu, . (2008) Short-term Safety and Tolerability of a Once-Daily Fixed-Dose Abacavir-Lamivudine Combination versus Twice-Daily Dosing of Abacavir and Lamivudine as Separate Components: Findings from the ALOHA Study. Pharmacotherapy 28:3, 314-322
Online publication date: 1-Apr-2008.
CrossRef
Jean-Michel Molina. (2008) Efficacy and Safety of Once-Daily Regimens in the Treatment of HIV Infection. Drugs 68:5, 567-578
Online publication date: 1-Feb-2008.
CrossRef
Geoffrey J Yuen, Steve Weller, Gary E Pakes. (2008) A Review of the Pharmacokinetics of Abacavir. Clinical Pharmacokinetics 47:6, 351-371
Online publication date: 1-Feb-2008.
CrossRef
Laura Waters, Mark Nelson, Sundhiya Mandalia, Mark Bower, Tom Powles, Brian Gazzard, and Justin Stebbing. (2008) The Risks and Incidence of K65R and L74V Mutations and Subsequent Virologic Responses. Clinical Infectious Diseases 46:1, 96-100
Online publication date: 1-Jan-2008.
Abstract-Full Text-PDF Version (236 kB)
Graham S Cooke. (2007) Evolution of adult antiretroviral therapy for programmatic delivery in Africa and the potential role for new therapeutic approaches. Therapy 4:6, 767-774
Online publication date: 1-Dec-2007.
CrossRef
Peter L Anderson, Jia-Hua Zheng, Tracy King, Lane R Bushman, Julie Predhomme, Amie Meditz, John Gerber, Courtney V Fletcher. (2007) Concentrations of zidovudine- and lamivudine-triphosphate according to cell type in HIV-seronegative adults. AIDS 21:14, 1849-1854
Online publication date: 1-Oct-2007.
CrossRef
Mark A Wainberg, Jorge L Martinez-Cajas, Bluma G Brenner. (2007) Strategies for the optimal sequencing of antiretroviral drugs toward overcoming and preventing drug resistance. Future HIV Therapy 1:3, 291-313
Online publication date: 1-Oct-2007.
CrossRef
L. Waters, M. Nelson. (2007) Why do patients fail HIV therapy?. International Journal of Clinical Practice 61:6, 983-990
Online publication date: 1-Jul-2007.
CrossRef
Firouz?? Bani-Sadr, Lise Denoeud, Patrice Morand, Fran??oise Lunel-Fabiani, Stanislas Pol, Patrice Cacoub, Christian Perronne, Fabrice Carrat. (2007) Early Virologic Failure in HIV-Coinfected Hepatitis C Patients Treated With the Peginterferon-Ribavirin Combination. JAIDS Journal of Acquired Immune Deficiency Syndromes 45:1, 123-125
Online publication date: 1-Jun-2007.
CrossRef
Bruce L. Gilliam, Mohammad M. Sajadi, Anthony Amoroso, Charles E. Davis, Farley R. Cleghorn, Robert R. Redfield. (2007) Tenofovir and Abacavir Combination Therapy: Lessons Learned from an Urban Clinic Population. AIDS Patient Care and STDs 21:4, 240-246
Online publication date: 1-May-2007.
CrossRef
Clare L Taylor, Edmund GL Wilkins. (2007) Abacavir/lamivudine fixed-dose combination tablet for the treatment of HIV-1 infection. Future Virology 2:1, 11-21
Online publication date: 1-Feb-2007.
CrossRef
Luz Martín-Carbonero, Paldma Gil, Teresa García-Benayas, Pablo Barreiro, Francisco Blanco, Carmen De Mendoza, Ivana Maida, Juan González-Lahoz, Vincent Soriano. (2007) Rate of Virologic Failure and Selection of Drug Resistance Mutations Using Different Triple Nucleos(t)ide Analogue Combinations in HIV-Infected Patients. AIDS Research and Human Retroviruses 22:12, 1231-1235
Online publication date: 1-Jan-2007.
CrossRef
Anton Pozniak. (2007) Initiation of antiretroviral therapy. Current Opinion in Internal Medicine 5:6, 594-604
Online publication date: 1-Jan-2007.
CrossRef
B Gazzard, . (2006) British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2006). HIV Medicine 7:8, 487-503
Online publication date: 1-Dec-2006.
CrossRef
Erik De Clercq. (2006) From adefovir to Atripla? via tenofovir, Viread? and Truvada?. Future Virology 1:6, 709-715
Online publication date: 1-Dec-2006.
CrossRef
David Rey, Magali Krebs, Marialuisa Partisani, Georgette Hess, Christine Cheneau, Mich??le Priester, Claudine Bernard-Henry, Erik de Mautort, Jean-Marie Lang. (2006) Virologic Response of Zidovudine, Lamivudine, and Tenofovir Disoproxil Fumarate Combination in Antiretroviral-Naive HIV-1???Infected Patients. JAIDS Journal of Acquired Immune Deficiency Syndromes PAP,
Online publication date: 1-Dec-2006.
CrossRef
NA Margot, B Lu, A Cheng, MD Miller, . (2006) Resistance development over 144 weeks in treatment-naive patients receiving tenofovir disoproxil fumarate or stavudine with lamivudine and efavirenz in Study 903*. HIV Medicine 7:7, 442-450
Online publication date: 1-Nov-2006.
CrossRef
John A Bartlett, Michael J Fath, Ralph DeMasi, Ashwaq Hermes, Joseph Quinn, Elsa Mondou, Franck Rousseau. (2006) An updated systematic overview of triple combination therapy in antiretroviral-naive HIV-infected adults. AIDS 20:16, 2051???2064
Online publication date: 1-Nov-2006.
CrossRef
Rebeca M Plank, Daniel R Kuritzkes. (2006) An update on HIV-1 antiretroviral resistance. Current Opinion in HIV and AIDS 1:5, 417-423
Online publication date: 1-Oct-2006.
CrossRef
Tomas Cihlar. (2006) Nucleotide HIV reverse transcriptase inhibitors: tenofovir and beyond. Current Opinion in HIV and AIDS 1:5, 373-379
Online publication date: 1-Oct-2006.
CrossRef
Paul A Pham, Joel E Gallant. (2006) Tenofovir disoproxil fumarate for the treatment of HIV infection. Expert Opinion on Drug Metabolism <html_ent glyph="@amp;" ascii="&amp;"/> Toxicology 2:3, 459-469
Online publication date: 1-Jul-2006.
CrossRef
Karen T. Tashima, Jennifer Adelson Mitty. (2006) Once-daily therapies for the treatment of HIV infection. Current HIV/AIDS Reports 3:2, 86-92
Online publication date: 1-Jul-2006.
CrossRef
(2006) Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa. AIDS 20:10, 1391???1399
Online publication date: 1-Jul-2006.
CrossRef
Rafik Samuel, Robert Bettiker, Byungse Suh. (2006) Antiretroviral therapy 2006: Pharmacology, applications, and special situations. Archives of Pharmacal Research 29:6, 431-458
Online publication date: 1-Jul-2006.
CrossRef
Bluma G Brenner, Maureen Oliveira, Florence Doualla-Bell, Daniela D Moisi, Michel Ntemgwa, Fernando Frankel, Max Essex, Mark A Wainberg. (2006) HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. AIDS 20:9, F9???F13
Online publication date: 1-Jul-2006.
CrossRef
Andrew Carr. (2006) Investigating New Antiretroviral Combinations. The Journal of Infectious Diseases 193:12, 1742-1742
Online publication date: 15-Jun-2006.
Citation-Full Text-PDF Version (139 kB)
Joel E. Gallant, Michael L. Lim, and Mark S. Shaefer. (2006) Reply to Carr. The Journal of Infectious Diseases 193:12, 1742-1743
Online publication date: 15-Jun-2006.
Citation-Full Text-PDF Version (139 kB)
Bruce L GILLIAM, Robert R REDFIELD, Richard Y ZHAO, Robert C GALLO. (2006) Commentary on “Prevalence and evolution of drug resistance HIV-1 variants in Henan, China”. Cell Research 15:11-12, 850-851
Online publication date: 1-Jan-2006.
CrossRef
Bruce L GILLIAM, Robert R REDFIELD. (2006) Approaches to antiretroviral therapy in China. Cell Research 15:11-12, 895-902
Online publication date: 1-Jan-2006.
CrossRef
Daniel R. Kuritzkes. (2005) Less than the Sum of Its Parts: Failure of a Tenofovir‐Abacavir‐Lamivudine Triple‐Nucleoside Regimen. The Journal of Infectious Diseases 192:11, 1867-1868
Online publication date: 1-Dec-2005.
Citation-Full Text-PDF Version (49 kB)

  • Presented in part: 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, 14–17 September 2003 (abstract H‐1722a); 44th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 30 October–2 November 2004 (abstract H‐567).

    Potential conflicts of interest: J.E.G. has served as a paid consultant for and has received honoraria from GlaxoSmithKline, Gilead Sciences, and Bristol‐Myers Squibb, the manufacturers of the drugs used in the study. He has also received research support from all 3 companies. W.G.W. conducts research that is sponsored by GlaxoSmithKline. B.Y. is on the speaker bureau and has received research support from GlaxoSmithKline. M.L.L., Q.L., L.R., J.J., and M.S.S. are all employed by and own stock in GlaxoSmithKline, which provided funding for the trial and is the manufacturer of abacavir, lamivudine, and zidovudine, which were used in the trial.

    Financial support: GlaxoSmithKline.

  • Study group members are listed after the text.

Back to Top
Close Popup