Research

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

Graham P Taylor¹ , Peter Goon^1,2 , Yoshitaka Furukawa³ , Hannah Green⁴ , Anna Barfield¹ , Angelina Mosley² , Hirohisa Nose³ , Abdel Babiker⁴ , Peter Rudge⁵ , Koichiro Usuku³ , Mitsuhiro Osame³ , Charles RM Bangham² and Jonathan N Weber¹

¹  Department of GU Medicine and Communicable Diseases, Faculty of Medicine, Imperial College, London, UK

²  Department of Immunology, Faculty of Medicine, Imperial College, London, UK

³  3^rd Department of Internal Medicine, University of Kagoshima, Kagoshima, Japan

⁴  Clinical Trials Unit, Medical Research Council, London, UK

⁵  The National Hospital for Neurology and Neurosurgery, London, UK

author email corresponding author email

Retrovirology 2006, 3:63doi:10.1186/1742-4690-3-63

Published:	19 September 2006

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.