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


CONCLUSIONS
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.
Taylor
Graham P
GP
Department of GU Medicine and Communicable Diseases, Faculty of Medicine, Imperial College, London, UK. g.p.taylor@imperial.ac.uk.
Goon
Peter
P
Furukawa
Yoshitaka
Y
Green
Hannah
H
Barfield
Anna
A
Mosley
Angelina
A
Nose
Hirohisa
H
Babiker
Abdel
A
Rudge
Peter
P
Usuku
Koichiro
K
Osame
Mitsuhiro
M
Bangham
Charles R M
CR
Weber
Jonathan N
JN
D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D049109:Cell Proliferation; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy*; D010919:Placebos; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects
D019380:Anti-HIV Agents; D010919:Placebos; D019259:Lamivudine; D015215:Zidovudine