To evaluate the safety and efficacy of didanosine (ddl) monotherapy and three different combinations of zidovudine (ZDV) and ddl 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 ddI 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 and adjusting for hemophilia status, prior ZDV treatment, and baseline CD4, there was a significant reduction in quantitative viral 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.
ARTICLES|
May 1, 1995
Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups
MV Ragni,
MV Ragni
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
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DA Amato,
DA Amato
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
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ML LoFaro,
ML LoFaro
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
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V DeGruttola,
V DeGruttola
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
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C Van Der Horst,
C Van Der Horst
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
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ME Eyster,
ME Eyster
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
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CM Kessler,
CM Kessler
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
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GF Gjerset,
GF Gjerset
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
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M Ho,
M Ho
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
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DM Parenti
DM Parenti
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
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Blood (1995) 85 (9): 2337–2346.
Citation
MV Ragni, DA Amato, ML LoFaro, V DeGruttola, C Van Der Horst, ME Eyster, CM Kessler, GF Gjerset, M Ho, DM Parenti; Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups. Blood 1995; 85 (9): 2337–2346. doi: https://doi.org/10.1182/blood.V85.9.2337.bloodjournal8592337
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