Low doses of zidovudine plus didanosine are less effective than higher doses of didanosine monotherapy

A randomized trial in patients pretreated with zidovudine

Philippe Sudre, Jean Philippe Chave, Christian Ruef, Anne Iten, Heiner C. Bucher, Pietro L. Vernazza, Hansjakob Furrer, Enos Bernasconi, Norberto Ceserani, Manuel Battegay, Jan Von Overbeck, Ignazio Cassis, Adriano Lazzarin, Victor Gabriel, Bernard J. Hirschel

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)629-633
Number of pages5
JournalClinical Microbiology and Infection
Volume3
Issue number6
Publication statusPublished - 1997

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Didanosine
Zidovudine
Acquired Immunodeficiency Syndrome
Pharmaceutical Preparations
Therapeutics
Opportunistic Infections
CD4 Lymphocyte Count
Group Psychotherapy
Randomized Controlled Trials
Demography
HIV
Confidence Intervals

Keywords

  • AIDS
  • Antiretroviral
  • Combination therapy
  • Didanosine
  • Drug dosage
  • HIV
  • Randomized trial
  • Zidovudine

ASJC Scopus subject areas

  • Microbiology (medical)
  • Microbiology

Cite this

Low doses of zidovudine plus didanosine are less effective than higher doses of didanosine monotherapy : A randomized trial in patients pretreated with zidovudine. / Sudre, Philippe; Chave, Jean Philippe; Ruef, Christian; Iten, Anne; Bucher, Heiner C.; Vernazza, Pietro L.; Furrer, Hansjakob; Bernasconi, Enos; Ceserani, Norberto; Battegay, Manuel; Von Overbeck, Jan; Cassis, Ignazio; Lazzarin, Adriano; Gabriel, Victor; Hirschel, Bernard J.

In: Clinical Microbiology and Infection, Vol. 3, No. 6, 1997, p. 629-633.

Research output: Contribution to journalArticle

Sudre, P, Chave, JP, Ruef, C, Iten, A, Bucher, HC, Vernazza, PL, Furrer, H, Bernasconi, E, Ceserani, N, Battegay, M, Von Overbeck, J, Cassis, I, Lazzarin, A, Gabriel, V & Hirschel, BJ 1997, 'Low doses of zidovudine plus didanosine are less effective than higher doses of didanosine monotherapy: A randomized trial in patients pretreated with zidovudine', Clinical Microbiology and Infection, vol. 3, no. 6, pp. 629-633.
Sudre, Philippe ; Chave, Jean Philippe ; Ruef, Christian ; Iten, Anne ; Bucher, Heiner C. ; Vernazza, Pietro L. ; Furrer, Hansjakob ; Bernasconi, Enos ; Ceserani, Norberto ; Battegay, Manuel ; Von Overbeck, Jan ; Cassis, Ignazio ; Lazzarin, Adriano ; Gabriel, Victor ; Hirschel, Bernard J. / Low doses of zidovudine plus didanosine are less effective than higher doses of didanosine monotherapy : A randomized trial in patients pretreated with zidovudine. In: Clinical Microbiology and Infection. 1997 ; Vol. 3, No. 6. pp. 629-633.
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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.",
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T1 - Low doses of zidovudine plus didanosine are less effective than higher doses of didanosine monotherapy

T2 - A randomized trial in patients pretreated with zidovudine

AU - Sudre, Philippe

AU - Chave, Jean Philippe

AU - Ruef, Christian

AU - Iten, Anne

AU - Bucher, Heiner C.

AU - Vernazza, Pietro L.

AU - Furrer, Hansjakob

AU - Bernasconi, Enos

AU - Ceserani, Norberto

AU - Battegay, Manuel

AU - Von Overbeck, Jan

AU - Cassis, Ignazio

AU - Lazzarin, Adriano

AU - Gabriel, Victor

AU - Hirschel, Bernard J.

PY - 1997

Y1 - 1997

N2 - 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.

AB - 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.

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KW - Antiretroviral

KW - Combination therapy

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KW - Drug dosage

KW - HIV

KW - Randomized trial

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