US EPA

7568937 

Journal Article 

Hydroxyurea toxicity combined with didanosine (ddI) in HIV-1-seropositive asymptomatic individuals 

Seminari, E; Lisziewicz, J; Tinelli, C; Foli, A; Lori, F; Maserati, R 

1999 

Yes 

International Journal of Clinical Pharmacology and Therapeutics
ISSN: 0946-1965 

37 

10 

514-518 

English 

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. Design: 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/μl. 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. 

Antiretroviral therapy; Didanosine; HIV infection; Hydroxyurea; Side-effects; amylase; didanosine; hemoglobin; hydroxyurea; triacylglycerol; abdominal pain; adult; alopecia; anemia; article; bone marrow suppression; clinical article; clinical trial; controlled clinical trial; controlled study; diarrhea; fatigue; female; human; human immunodeficiency virus 1; human immunodeficiency virus infection; leukocyte count; lymphocyte count; male; nausea; neutropenia; phase 2 clinical trial; randomized controlled trial; side effect; thrombocytopenia; triacylglycerol blood level; Adult; Anti-HIV Agents; Bone Marrow; Didanosine; Drug Synergism; Drug Therapy, Combination; Female; HIV Seropositivity; HIV-1; Humans; Hydroxyurea; Immunosuppressive Agents; Male; Middle Aged; Retrospective Studies