Background Hydroxyurea is believed to inhibit human immunodeficiency virus
type 1 (HIV-1) in HIV disease by decreasing the amount of intracellular deo
xynucleotides needed for viral replication. A plasma concentration of 400 m
u mol L-1 is tolerated in oncological diseases. The present study focused o
n the possible interference of hydroxyurea with antigen-dependent T-cell ac
tivation as an alternative explanation for inhibiting HIV replication in vi
vo.
Methods The effect of hydroxyurea on common antigen-induced cell proliferat
ion was studied in peripheral blood mononuclear cells (PBMC) in vitro.
Results Hydroxyurea inhibited Candida albicans-induced cell proliferation a
t a low concentration (1 mu mol L-1), while at least 10 mu mol L-1 was requ
ired to block HIV-1 replication in phytohaemagglutinin (PHA)-stimulated PBM
C.
Conclusion Hydroxyurea inhibits antigen-induced lymphoproliferation in vitr
o at a concentration at which it does not inhibit PHA-induced HIV replicati
on. Hydroxyurea may inhibit HIV-1 in CD4(+) T cells in vivo not only by dec
reasing the amount of intracellular deoxynucleotides, but more specifically
by interfering with antigen-dependent T-cell activation, thereby causing a
reduction in the number of HIV target cells.