Data from comparative trials involving more than 500 patients indicate that
hydroxyurea is safe and augments suppression of HIV-1 replication when use
d in combination with didanosine or didanosine/stavudine as initial therapy
or in patients without extensive antiretroviral experience. Additional stu
dies will determine the optimum dosage and schedule for hydroxyurea and its
effects when used with other agents and in patients with advanced disease
or extensive pretreatment Activities of hydroxyurea include inhibition of H
IV-1 in active and resting CD4 lymphocytes and macrophages, potentiation of
the activity of nucleoside reverse transcriptase inhibitors (NRTIs), compe
nsation for resistance to adenosine analogue NRTIs, and potential increased
phosphorylation of pyrimidine NRTIs. Recent attention, however, has focuse
d on the potential immunomodulatory effects of hydroxyurea. The cytostatic
effect of this agent on both CD4 and CD8 T cells may provide immunological
benefits by reducing immune system overactivation, thus preventing both CD8
T cell exhaustion and CD4 T cell depletion. Accumulating evidence indicate
s that hydroxy-urea-containing regimens may be associated with decreased le
vels of activated CD8 T cells, increased levels of naive CD4 and CD8 T cell
s, and preservation of the HIV-1-specific immune response. Further study of
the potential for beneficial immunomodulation with hydroxyurea-containing
regimens is needed to ascertain the clinical implications of these initial
findings.