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.
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.
Taylor
G P
GP
Department of Genito-Urinary Medicine and Communicable Diseases, Division of Medicine, Imperial College School of Medicine, London W2 1PG, United Kingdom.
Hall
S E
SE
Navarrete
S
S
Michie
C A
CA
Davis
R
R
Witkover
A D
AD
Rossor
M
M
Nowak
M A
MA
Rudge
P
P
Matutes
E
E
Bangham
C R
CR
Weber
J N
JN
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016384:Consensus Sequence; D004279:DNA, Viral / Q000187:drug effects; D005260:Female; D016356:Gene Products, tax / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019380:Anti-HIV Agents; D004279:DNA, Viral; D016356:Gene Products, tax; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase