title: Low doses of zidovudine plus didanosine are less effective than higher doses of didanosine monotherapy: a randomized trial in patients pretreated with zidovudine.
abstract: OBJECTIVE: To compare the clinical efficacy and tolerance of didanosine (ddl) monotherapy with low-dose zidovudine/didanosine (AZT/ddl) therapy among HIV-infected patients previously treated with AZT. METHODS: A randomized controlled trial was carried out of ddl 400 mg daily versus AZT/ddl 300/200 mg daily among patients with CD4 cell counts </=350 mm3 and prior AZT treatment for at least 16 weeks. Fifty eight patients received ddl monotherapy and 66 combined treatment. RESULTS: Patients were similar with respect to demographic, clinical and laboratory characteristics, and prior AZT treatment. Median duration of follow-up was 17.3 months. In the ddl group, 20 patients (34%) discontinued treatment because of toxicity, compared to 19 (29%) in the AZT/ddl group (p=0.38). There was no statistically significant difference in CD4 change between the two groups. In the ddl group, 16 patients (28%) developed a clinical endpoint (death or AIDS-defining opportunistic infection), compared to 33 (50%) in the combined therapy group (relative risk 1.8; 95% confidence interval 1.1-2.9; p=0.01). CONCLUSIONS: For fairly advanced AZT-pretreated patients, monotherapy with ddl was clinically and statistically superior to the low-dose AZT/ddl combination in preventing AIDS-defining illness and death. When access to drugs is limited, e.g. in under-resourced countries, combining available drugs and reducing dosage may be less effective than a single drug at the conventional dosage.
authors.affiliation: University Hospital, Geneva.
authors.forename: Philippe
authors.initials: P
authors.lastname: Sudre
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Chave
authors.forename: Christian
authors.initials: C
authors.lastname: Ruef
authors.forename: Anne
authors.initials: A
authors.lastname: Iten
authors.forename: Heiner C.
authors.initials: HC
authors.lastname: Bucher
authors.forename: Pietro L.
authors.initials: PL
authors.lastname: Vernazza
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Norberto
authors.initials: N
authors.lastname: Ceserani
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Jan
authors.initials: J
authors.lastname: Von Overbeck
authors.forename: Ignazio
authors.initials: I
authors.lastname: Cassis
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Victor
authors.initials: V
authors.lastname: Gabriel
authors.forename: Bernard J.
authors.initials: BJ
authors.lastname: Hirschel