Document 0162
 DOCN  M9580162
 TI    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.
 DT    9506
 AU    Ragni MV; Amato DA; LoFaro ML; DeGruttola V; Van Der Horst C; Eyster ME;
       Kessler CM; Gjerset GF; Ho M; Parenti DM; et al; Department of Medicine,
       University of Pittsburgh School of; Medicine, PA, USA.
 SO    Blood. 1995 May 1;85(9):2337-46. Unique Identifier : AIDSLINE
       MED/95244853
 AB    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.
 DE    Adult  Comparative Study  CD4 Lymphocyte Count/DRUG EFFECTS
       Didanosine/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC  USE
       Drug Therapy, Combination  Female  Hemophilia/*COMPLICATIONS/IMMUNOLOGY
       Hepatitis, Toxic/ETIOLOGY  Human  HIV Core Protein p24/BLOOD  HIV
       Infections/COMPLICATIONS/*DRUG THERAPY/IMMUNOLOGY/VIROLOGY
       HIV-1/ISOLATION & PURIF  Male  Safety  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  Treatment Outcome  Viremia/DRUG THERAPY/VIROLOGY
       Zidovudine/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC  USE
       CLINICAL TRIAL  CLINICAL TRIAL, PHASE I  CLINICAL TRIAL, PHASE II
       JOURNAL ARTICLE  RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).