Journal of Infection
Volume 61, Issue 4 , Pages 346-350 , October 2010

Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R

  • C. Stephan

      Affiliations

    • HIVCENTER at Building No. 68, Johann Wolfgang Goethe-University Hospital, Department of Internal Medicine II, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
    • Corresponding Author InformationCorresponding author. Tel.: + 49 69 6301 7680; fax: +49 69 6301 5712.
    • ,
  • B. Dauer

      Affiliations

    • HIVCENTER at Building No. 68, Johann Wolfgang Goethe-University Hospital, Department of Internal Medicine II, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
    • ,
  • M. Bickel

      Affiliations

    • HIVCENTER at Building No. 68, Johann Wolfgang Goethe-University Hospital, Department of Internal Medicine II, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
    • ,
  • A. Haberl

      Affiliations

    • HIVCENTER at Building No. 68, Johann Wolfgang Goethe-University Hospital, Department of Internal Medicine II, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
    • ,
  • L. Locher

      Affiliations

    • Infektiologikum Frankfurt, Germany
    • ,
  • A. Müller

      Affiliations

    • Infektiologikum Frankfurt, Germany
    • ,
  • S. Klauke

      Affiliations

    • Infektiologikum Frankfurt, Germany
    • ,
  • A. Berger

      Affiliations

    • Institute of Medical Virology at the Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany
    • ,
  • H.-W. Doerr

      Affiliations

    • Institute of Medical Virology at the Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany
    • ,
  • M. Stürmer

      Affiliations

    • Institute of Medical Virology at the Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany
    • M.S. and S.S. contributed equally to this article.
    • ,
  • S. Staszewski

      Affiliations

    • HIVCENTER at Building No. 68, Johann Wolfgang Goethe-University Hospital, Department of Internal Medicine II, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
    • M.S. and S.S. contributed equally to this article.
    • ,
  • for the Frankfurt Cohort Study

,Accepted 14 June 2010.

References 

  1. Gallant JE, Rodriguez AE, Weinberg WG, Young B, Berger DS, Lim ML, et al. Early virologic non-response to tenofovir, abacavir, and lamivudine in HIV-infected antiretroviral-naive subjects. J Infect Dis. 2005;192:1921–1930
  2. Maitland D, Moyle G, Hand J, Mandalia S, Boffito M, Nelson M, et al. Early virologic failure in HIV-1 infected subjects on didanosine/tenofovir/efavirenz: 12-week results from a randomized trial. AIDS. 2005;19:1183–1188
  3. Rey D, Hoen B, Chavanet P, Schmitt MP, Hoizey G, Meyer P, et al. High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients. J Antimicrob Chemother. 2009;63:380–388
  4. Ntemgwa ML, Toni T, Brenner BG, Oliveira M, Asahchop EL, Moisi D, et al. Nucleoside and nucleotide analogs select in culture for different patterns of drug resistance in human immunodeficiency virus types 1 and 2. Antimicrobial Agents Chemother. 2009;53:708–715
  5. Miller MD, McColl DJ, White KL, Parkin NT. Genotypic and phenotypic characterization of patient-derived HIV-1 isolates containing the K65R mutation in reverse transcriptase (RT). 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. (Chicago) September 2003 [Abstract H-904].
  6. Lani ER, Scott J, Ait-Khaled M, Craig C, Alcorn T, Irlbeck D, et al. Prevalence of mutations associated with resistance to antiretroviral therapy from 1999–2002. 10th Conference on Retroviruses and Opportunistic Infections (Boston) February 2003 [Abstract 635].
  7. Gallant JE, Staszewski S, Pozniak AL, DeJesus E, Suleiman JM, Miller MD, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. J Am Med Assoc. 2004;292:191–201
  8. McColl DJ, Margot NA, Wulfsohn M, Coakley DF, Cheng AK, Miller MD. Patterns of resistance emerging in HIV-1 from antiretroviral-experienced patients undergoing intensification therapy with tenofovir disoproxil fumarate. J Acquir Immune Defic Syndr Hum Retrovirol. 2004;37:1340–1349
  9. Gupta R, Hill A, Sawyer AW, Pillay D. Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: a systematic review of clinical trials. Clin Infect Dis. 2008;47:712–722
  10. Ferradini L, Jeannin A, Pinoges L, Izopet J, Odhiambo D, Mankhambo L, et al. Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment. Lancet. 2006;367:1335–1342
  11. White KL, Margot NA, Ly JK, Chen JM, Ray AS, Pavelko M, et al. A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. AIDS. 2005;19:1751–1760
  12. Kuritzkes DR, Marschner I, Johnson VA, Bassett R, Eron JJ, Fischl MA, et al. Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. AIDS. 1999;13:685–694
  13. Frankel FA, Invernizzi CF, Oliveira M, Wainberg MA. Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations. AIDS. 2007;21:665–675
  14. Parikh UM, Barnas DC, Faruki H, Mellors JW. Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level. J Infect Dis. 2006;194:651–660
  15. Parikh UM, Zelina S, Sluis-Cremer N, Mellors JW. Molecular mechanisms of bidirectional antagonism between K65R and thymidine analogue mutations in HIV-1 reverse transcriptase. AIDS. 2007;21:1405–1414
  16. Wirden M, Malet I, Derache A, Marcelin AG, Roquebert B, Simon A, et al. Clonal analyses of HIV quasispecies in patients harbouring plasma genotype with K65R mutation associated with thymidine analogue mutations or L74V substitution. AIDS. 2005;19:630–632

PII: S0163-4453(10)00175-1

doi: 10.1016/j.jinf.2010.06.008

Journal of Infection
Volume 61, Issue 4 , Pages 346-350 , October 2010

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