Hydroxyurea toxicity combined with didanosine (ddl) in HIV-1-seropositive asymptomatic individuals.
OBJECTIVE
Hydroxyurea, a carbamate compound widely used for the treatment of myeloproliferative disorders, has been investigated in several clinical trials conducted in the setting of HIV infection, where it is given in combination regimens almost always containing didanosine (ddI). Hydroxyurea mainly acts as a ribonucleotide reductase inhibitor and can positively modulate the activity of several pyrimidine and purine analogues. Due to its inhibition of DNA synthesis, the main side-effect of hydroxyurea is represented by myelosuppression.


METHODS
The toxicity profile of hydroxyurea plus didanosine (ddI) has been investigated in 40 asymptomatic HIV-positive patients with a baseline CD4+ absolute count between 250 and 500 cells/microl. Bone marrow function tests and adverse events occurring during the trial were analyzed.


RESULTS
No major toxic event according to WHO classification was registered. At the dosage of 500 mg twice a day, hydroxyurea could be safely administered for at least 40 weeks of therapy. Minimal reversible bone marrow depression was noted in 2 patients. Even though reductions observed in white blood cell count, lymphocyte count and hemoglobin were statistically significant, they did not have any clinical relevance.


CONCLUSIONS
Hydroxyurea seems to be well-tolerated and devoid of severe toxicity effects when used in asymptomatic HIV-positive subjects.
Seminari
E
E
Clinica delle Malattie Infettive, Policlinico San Matteo, Pavia, Italy.
Lisziewicz
J
J
Tinelli
C
C
Foli
A
A
Lori
F
F
Maserati
R
R
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D016049:Didanosine / Q000009:adverse effects* / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D019380:Anti-HIV Agents; D007166:Immunosuppressive Agents; D016049:Didanosine; D006918:Hydroxyurea