Zidovudine plus lamivudine in human T-lymphotropic virus type-I-associated myelopathy: a randomised trial

Title: Zidovudine plus lamivudine in human T-lymphotropic virus type-I-associated myelopathy: a randomised trial
Author(s): Taylor, GP
Goon, P
Furukawa, Y
Green, H
Barfield, A
Mosley, A
Nose, H
Babiker, A
Rudge, P
Usuku, K
Osame, M
Bangham, CR
Weber, JN
Item Type: Journal Article
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 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.
Publication Date: 19-Sep-2006
Date of Acceptance: 19-Sep-2006
URI: http://hdl.handle.net/10044/1/50811
DOI: https://dx.doi.org/10.1186/1742-4690-3-63
ISSN: 1742-4690
Publisher: BioMed Central
Journal / Book Title: Retrovirology
Volume: 3
Copyright Statement: © Taylor et al; licensee BioMed Central Ltd. 2006. This article is published under license to 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.
Keywords: Science & Technology
Life Sciences & Biomedicine
Virology
VIROLOGY
BLOOD MONONUCLEAR-CELLS
TROPICAL SPASTIC PARAPARESIS
CENTRAL-NERVOUS-SYSTEM
HTLV-I
PERIPHERAL-BLOOD
REVERSE-TRANSCRIPTASE
LEUKEMIA
INFECTION
TRANSMISSION
REPLICATION
Aged
Anti-HIV Agents
Cell Proliferation
Double-Blind Method
Drug Therapy, Combination
Female
Humans
Lamivudine
Male
Middle Aged
Paraparesis, Tropical Spastic
Placebos
Viral Load
Zidovudine
Humans
Paraparesis, Tropical Spastic
Lamivudine
Zidovudine
Placebos
Anti-HIV Agents
Drug Therapy, Combination
Viral Load
Double-Blind Method
Cell Proliferation
Aged
Middle Aged
Female
Male
Science & Technology
Life Sciences & Biomedicine
Virology
VIROLOGY
BLOOD MONONUCLEAR-CELLS
TROPICAL SPASTIC PARAPARESIS
CENTRAL-NERVOUS-SYSTEM
HTLV-I
PERIPHERAL-BLOOD
REVERSE-TRANSCRIPTASE
LEUKEMIA
INFECTION
TRANSMISSION
REPLICATION
1103 Clinical Sciences
Virology
Publication Status: Published
Article Number: ARTN 63
Appears in Collections:Department of Medicine
Faculty of Medicine



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