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.

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Blood. 1995 May 1;85(9):2337-46. Unique Identifier : AIDSLINE MED/95244853
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.

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.

Keywords: 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
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