Zidovudine plus lamivudine in Human T-Lymphotropic Virus type-I-associated myelopathy: a randomised trial

Taylor, Goon Peter, Furukawa Yoshitaka, Green Hannah, Barfield Anna, Mosley Angelina, Nose Hirohisa, Babiker Abdel, Rudge Peter, Usuku Koichiro, Osame Mitsuhiro, Bangham, Weber

Description

No therapies have been proven to persistently improve the outcome of HTLV-I-associated myelopathy. Clinical benefit has been reported with zidovudine and with lamivudine in observational studies. We therefore conducted a randomised, double blind, placebo controlled study of six months combination therapy with these nucleoside analogues in sixteen patients. Results Primary outcomes were change in HTLV-I proviral load in PBMCs and clinical measures. Secondary endpoints were changes in T-cell subsets and markers of activation and proliferation. Six patients discontinued zidovudine. No significant changes in pain, bladder function, disability score, gait, proviral load or markers of T-cell activation or proliferation were seen between the two arms. Active therapy was associated with an unexplained decrease in CD8 and non-T lymphocyte counts. Conclusion Failure to detect clinical improvement may have been due irreversible nerve damage in these patients with a long clinical history and future studies should target patients presenting earlier. The lack of virological effect but may reflect a lack of activity of these nucleoside analogues against HTLV-I RT in vivo , inadequate intracellular concentrations of the active moiety or the contribution of new cell infection to maintaining proviral load at this stage of infection may be relatively small masking the effects of RT inhibition.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2006
• Nombre de lectures: 33

Extrait

Retrovirology

BioMedCentral

Open Access Research Zidovudine plus lamivudine in Human T-Lymphotropic Virus type-I-associated myelopathy: a randomised trial 1 1,2 3 4 Graham P Taylor* , Peter Goon , Yoshitaka Furukawa , Hannah Green , 1 2 3 4 Anna Barfield , Angelina Mosley , Hirohisa Nose , Abdel Babiker , 5 3 3 2 Peter Rudge , Koichiro Usuku , Mitsuhiro Osame , Charles RM Bangham 1 and Jonathan N Weber

1 2 Address: Department of GU Medicine and Communicable Diseases, Faculty of Medicine, Imperial College, London, UK, Department of 3 Immunology, Faculty of Medicine, Imperial College, London, UK, 3rd Department of Internal Medicine, University of Kagoshima, Kagoshima, 4 5 Japan, Clinical Trials Unit, Medical Research Council, London, UK and The National Hospital for Neurology and Neurosurgery, London, UK

Email: Graham P Taylor*  [e-mail]; Peter Goon  [e-mail]; Yoshitaka Furukawa  [e-mail]u.ac.jp; Hannah Green  [e-mail]; Anna Barfield  [e-mail]; Angelina Mosley  [e-mail]; Hirohisa Nose  [e-mail]u.ac.jp; Abdel Babiker  [e-mail]; Peter Rudge  [e-mail]; Koichiro Usuku  space[e-mail]u.ac.jp; Mitsuhiro Osame  [e-mail]u.ac.jp; Charles RM Bangham  [e-mail]; Jonathan N Weber  [e-mail] * Corresponding author

Published: 19 September 2006 Received: 21 August 2006 Accepted: 19 September 2006 Retrovirology2006,3:63 doi:10.1186/1742-4690-3-63 This article is available from: http://www.retrovirology.com/content/3/1/63 © 2006 Taylor et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background:No therapies have been proven to persistently improve the outcome of HTLV-I- associated myelopathy. Clinical benefit has been reported with zidovudine and with lamivudine in observational studies. We therefore conducted a randomised, double blind, placebo controlled study of six months combination therapy with these nucleoside analogues in sixteen patients. Results:Primary outcomes were change in HTLV-I proviral load in PBMCs and clinical measures. Secondary endpoints were changes in T-cell subsets and markers of activation and proliferation. Six patients discontinued zidovudine. No significant changes in pain, bladder function, disability score, gait, proviral load or markers of T-cell activation or proliferation were seen between the two arms. Active therapy was associated with an unexplained decrease in CD8 and non-T lymphocyte counts.

Conclusion:Failure to detect clinical improvement may have been due irreversible nerve damage in these patients with a long clinical history and future studies should target patients presenting earlier. The lack of virological effect but may reflect a lack of activity of these nucleoside analogues against HTLV-I RTin vivo, inadequate intracellular concentrations of the active moiety or the contribution of new cell infection to maintaining proviral load at this stage of infection may be relatively small masking the effects of RT inhibition.

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