Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection
Document Type
Journal Article
Publication Date
5-1-1995
Journal
Blood
Volume
85
Issue
9
DOI
10.1182/blood.v85.9.2337.bloodjournal8592337
Abstract
To evaluate the safety and efficacy of didanosine (ddI) monotherapy and three different combinations of zidovudine (ZDV) and ddI in asymptomatic human immunodeficiency virus-1 (HIV-1) infection, we conducted an open- label, phase I/II study in 126 asymptomatic HIV-1-infected hemophilic and nonhemophilic subjects with a CD4 count of 200 to 500/mm3 stratified for prior zidovudine treatment and baseline CD4 count. Study arms included arm A, low-dose combination (ZDV 150 mg and ddl 134 mg, daily); arm B, moderate- dose combination (ZDV 300 mg and ddl 334 mg, daily); arm C, high-dose combination (ZDV 600 mg and ddl 500 mg, daily), and arm D, ddl monotherapy (ddl 500 mg, daily). Earlier, more frequent hepatotoxicity was experienced by hemophilic subjects (P = .008), but there were no differences in toxicity between treatment arms (P = .51), nor were there any differences in the rate of development of clinical endpoints by treatment (P = .41). Smaller median CD4 increases occurred over the first 12 weeks for arms A and D, 44/mm3 and 42/mm3, than arms B and C, 105/mm3 and 114/mm3, respectively, (P = .015). Hemophilia status (P = .0004) and prior ZDV experience (P = .044) independently predicted weaker CD4 responses during the first 12 weeks of treatment. Using a regression model end adjusting for hemophilia status, prior ZDV treatment, and baseline CD4, there was a significant reduction in quantitative vital load from baseline by week 12 for all treatment arms combined (P = .0001), with significantly lower median percent reduction for arm A (56.3%) than arms B, C, and D (94.6%, 98.5%, and 91.9%, respectively, P = .015). Although greater hepatoxicity and weaker CD4 responses occur in hemophilic subjects, didanosine monotherapy and combination therapy with zidovudine are safe and effective in asymptomatic HIV-1-infected patients.
APA Citation
Ragni, M., Amato, D., LoFaro, M., DeGruttola, V., Van Der Horst, C., Eyster, M., Kessler, C., Gjerset, G., Ho, M., Parenti, D., Dafni, U., Rasheed, S., Korvick, J., & Merigan, T. (1995). Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. Blood, 85 (9). http://dx.doi.org/10.1182/blood.v85.9.2337.bloodjournal8592337