title: 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.
abstract: 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.
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
authors.forename: M V
authors.initials: MV
authors.lastname: Ragni
authors.forename: D A
authors.initials: DA
authors.lastname: Amato
authors.forename: M L
authors.initials: ML
authors.lastname: LoFaro
authors.forename: V
authors.initials: V
authors.lastname: DeGruttola
authors.forename: C
authors.initials: C
authors.lastname: Van Der Horst
authors.forename: M E
authors.initials: ME
authors.lastname: Eyster
authors.forename: C M
authors.initials: CM
authors.lastname: Kessler
authors.forename: G F
authors.initials: GF
authors.lastname: Gjerset
authors.forename: M
authors.initials: M
authors.lastname: Ho
authors.forename: D M
authors.initials: DM
authors.lastname: Parenti
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D016049:Didanosine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006467:Hemophilia A / Q000150:complications* / Q000276:immunology; D006801:Humans; D008297:Male; D012449:Safety; D016896:Treatment Outcome; D014766:Viremia / Q000188:drug therapy / Q000821:virology; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D016655:HIV Core Protein p24; D015215:Zidovudine; D016049:Didanosine