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Journal of Virology, December 1999, p. 10289-10295, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Effect of Lamivudine on Human T-Cell Leukemia Virus Type 1 (HTLV-1) DNA Copy Number, T-Cell Phenotype, and Anti-Tax Cytotoxic T-Cell Frequency in Patients with HTLV-1-Associated Myelopathy

G. P. Taylor,1,* S. E. Hall,2 S. Navarrete,2 C. A. Michie,3 R. Davis,1 A. D. Witkover,2 M. Rossor,4 M. A. Nowak,5,dagger P. Rudge,6 E. Matutes,7 C. R. M. Bangham,2 and J. N. Weber1

Department of Genito-Urinary Medicine and Communicable Diseases, Division of Medicine,1 and Department of Immunology, Division of Investigative Science,2 Imperial College School of Medicine, London W2 1PG, Department of Paediatrics, Ealing Hospital NHS Trust, Ealing, Middlesex UB1 3HW,3 Department of Neurology, St. Mary's Hospital NHS Trust, London W2 1NY,4 Department of Zoology, University of Oxford, Oxford OX1 3PS,5 National Hospital for Neurology and Neurosurgery, London WC1N 3BG,6 and Academic Department of Haematology, Royal Marsden Hospital, London SW3,7 United Kingdom

Received 22 March 1999/Accepted 4 September 1999

Patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) typically have a high HTLV-1 proviral load in peripheral blood mononuclear cells and abundant, activated HTLV-1-specific cytotoxic T lymphocytes (CTLs). No effective treatment for HAM/TSP has been described so far. We report a 10-fold reduction in viral DNA for five patients with HAM/TSP during treatment with the reverse transcriptase inhibitor lamivudine. In one patient with recent-onset HAM/TSP, the reduction in viral DNA was associated with a fall in the frequency of CTLs specific to two peptides in the immunodominant viral antigen Tax. The half-life of peripheral blood mononuclear cell populations was estimated from changes in viral DNA copy number, CTL frequency, reduction in CD25 expression, and the loss of dicentric chromosomes following radiation-induced damage. Each of these four different techniques indicated a cellular half-life of approximately 3 days consistent with continuous lymphocyte replication and destruction. These results indicate that viral replication through reverse transcription significantly contributes to the maintenance of HTLV-1 viral DNA load. The relative contribution of proliferation versus replication may vary between infected people.

* Corresponding author. Mailing address: Department of Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, Norfolk Place, London W2 1PG, United Kingdom. Phone and fax: 44 171 886 6738. E-mail: g.p.taylor{at}ic.ac.uk.

dagger Present address: Institute for Advanced Study, Princeton, NJ 08540.

Journal of Virology, December 1999, p. 10289-10295, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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