Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine: A randomized, double-blind clinical trial

Spotswood L. Spruance, Andrew T. Pavia, Dolores Peterson, Allison Berry, Richard Pollard, Thomas F. Patterson, Ian Frank, Scot C. Remick, Melanie Thompson, Rodger David MacArthur, G. E. Morey, Carlos H. Ramirez-Ronda, Barry M. Bernstein, Donna E. Sweet, Lawrence Crane, Eskild A. Peterson, Constance T. Pachucki, Stephen L. Green, Jerry Brand, Adan RiosLisa M. Dunkle, Anne Cross, Michael J. Brown, Peter Ingraham, Ronald Gugliotti, Andrew H. Schindzielorz, Laurie Smaldone

Research output: Contribution to journalArticle

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Abstract

Objective: To determine the benefits of switching to didanosine compared with continuing zidovudine among patients infected with human immunodeficiency virus (HIV) who have previously used zidovudine and have signs of clinical deterioration. Design: Randomized, double-blind, two- armed, parallel, comparative clinical trial with a blinded, compassionate crossover provision at 12 weeks. Setting: Outpatient clinics at 19 tertiary care medical centers. Patients: 312 patients infected with HIV who had received zidovudine for 6 months or more, had CD4 cell counts of 300/mm3 or less, and had signs of clinical deterioration within 12 weeks before study entry. Intervention: Peroral didanosine tablets (600 mg/d adjusted for weight, 'high dose') or zidovudine capsules (600 mg/d). Measurements: Primary study end points were death, a new acquired immunodeficiency syndrome (AIDS)- defining event, or the combination of two new or recurrent HIV-related diagnoses with a 50% decrease in CD4 cells. Results: Switching to didanosine was associated with fewer end points than continuing zidovudine (relative risk [RR] for zidovudine:didanosine = 1.5; 95% Cl, 1.1 to 2.0). This benefit was consistent across subgroups of patients with either AIDS-related complex or AIDS and was most apparent among those with a CD4 count at entry of 100/mm3 or more (RR = 2.2; Cl, 1.1 to 4.4). Conclusions: This study shows a positive treatment effect for switching from zidovudine to didanosine among patients with either AIDS-related complex or AIDS and validates the common practice of using clinical signs or a decrease in the CD4 count as an indication for changing therapy.

Original languageEnglish (US)
Pages (from-to)360-368
Number of pages9
JournalAnnals of Internal Medicine
Volume120
Issue number5
DOIs
StatePublished - Mar 1 1994
Externally publishedYes

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Didanosine
Zidovudine
Clinical Trials
HIV
Acquired Immunodeficiency Syndrome
CD4 Lymphocyte Count
Ambulatory Care Facilities
Tertiary Care Centers
Tablets
Capsules
Weights and Measures
Therapeutics

ASJC Scopus subject areas

  • Internal Medicine

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Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine : A randomized, double-blind clinical trial. / Spruance, Spotswood L.; Pavia, Andrew T.; Peterson, Dolores; Berry, Allison; Pollard, Richard; Patterson, Thomas F.; Frank, Ian; Remick, Scot C.; Thompson, Melanie; MacArthur, Rodger David; Morey, G. E.; Ramirez-Ronda, Carlos H.; Bernstein, Barry M.; Sweet, Donna E.; Crane, Lawrence; Peterson, Eskild A.; Pachucki, Constance T.; Green, Stephen L.; Brand, Jerry; Rios, Adan; Dunkle, Lisa M.; Cross, Anne; Brown, Michael J.; Ingraham, Peter; Gugliotti, Ronald; Schindzielorz, Andrew H.; Smaldone, Laurie.

In: Annals of Internal Medicine, Vol. 120, No. 5, 01.03.1994, p. 360-368.

Research output: Contribution to journalArticle

Spruance, SL, Pavia, AT, Peterson, D, Berry, A, Pollard, R, Patterson, TF, Frank, I, Remick, SC, Thompson, M, MacArthur, RD, Morey, GE, Ramirez-Ronda, CH, Bernstein, BM, Sweet, DE, Crane, L, Peterson, EA, Pachucki, CT, Green, SL, Brand, J, Rios, A, Dunkle, LM, Cross, A, Brown, MJ, Ingraham, P, Gugliotti, R, Schindzielorz, AH & Smaldone, L 1994, 'Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine: A randomized, double-blind clinical trial', Annals of Internal Medicine, vol. 120, no. 5, pp. 360-368. https://doi.org/10.7326/0003-4819-120-5-199403010-00002
Spruance, Spotswood L. ; Pavia, Andrew T. ; Peterson, Dolores ; Berry, Allison ; Pollard, Richard ; Patterson, Thomas F. ; Frank, Ian ; Remick, Scot C. ; Thompson, Melanie ; MacArthur, Rodger David ; Morey, G. E. ; Ramirez-Ronda, Carlos H. ; Bernstein, Barry M. ; Sweet, Donna E. ; Crane, Lawrence ; Peterson, Eskild A. ; Pachucki, Constance T. ; Green, Stephen L. ; Brand, Jerry ; Rios, Adan ; Dunkle, Lisa M. ; Cross, Anne ; Brown, Michael J. ; Ingraham, Peter ; Gugliotti, Ronald ; Schindzielorz, Andrew H. ; Smaldone, Laurie. / Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine : A randomized, double-blind clinical trial. In: Annals of Internal Medicine. 1994 ; Vol. 120, No. 5. pp. 360-368.
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abstract = "Objective: To determine the benefits of switching to didanosine compared with continuing zidovudine among patients infected with human immunodeficiency virus (HIV) who have previously used zidovudine and have signs of clinical deterioration. Design: Randomized, double-blind, two- armed, parallel, comparative clinical trial with a blinded, compassionate crossover provision at 12 weeks. Setting: Outpatient clinics at 19 tertiary care medical centers. Patients: 312 patients infected with HIV who had received zidovudine for 6 months or more, had CD4 cell counts of 300/mm3 or less, and had signs of clinical deterioration within 12 weeks before study entry. Intervention: Peroral didanosine tablets (600 mg/d adjusted for weight, 'high dose') or zidovudine capsules (600 mg/d). Measurements: Primary study end points were death, a new acquired immunodeficiency syndrome (AIDS)- defining event, or the combination of two new or recurrent HIV-related diagnoses with a 50{\%} decrease in CD4 cells. Results: Switching to didanosine was associated with fewer end points than continuing zidovudine (relative risk [RR] for zidovudine:didanosine = 1.5; 95{\%} Cl, 1.1 to 2.0). This benefit was consistent across subgroups of patients with either AIDS-related complex or AIDS and was most apparent among those with a CD4 count at entry of 100/mm3 or more (RR = 2.2; Cl, 1.1 to 4.4). Conclusions: This study shows a positive treatment effect for switching from zidovudine to didanosine among patients with either AIDS-related complex or AIDS and validates the common practice of using clinical signs or a decrease in the CD4 count as an indication for changing therapy.",
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T1 - Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine

T2 - A randomized, double-blind clinical trial

AU - Spruance, Spotswood L.

AU - Pavia, Andrew T.

AU - Peterson, Dolores

AU - Berry, Allison

AU - Pollard, Richard

AU - Patterson, Thomas F.

AU - Frank, Ian

AU - Remick, Scot C.

AU - Thompson, Melanie

AU - MacArthur, Rodger David

AU - Morey, G. E.

AU - Ramirez-Ronda, Carlos H.

AU - Bernstein, Barry M.

AU - Sweet, Donna E.

AU - Crane, Lawrence

AU - Peterson, Eskild A.

AU - Pachucki, Constance T.

AU - Green, Stephen L.

AU - Brand, Jerry

AU - Rios, Adan

AU - Dunkle, Lisa M.

AU - Cross, Anne

AU - Brown, Michael J.

AU - Ingraham, Peter

AU - Gugliotti, Ronald

AU - Schindzielorz, Andrew H.

AU - Smaldone, Laurie

PY - 1994/3/1

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N2 - Objective: To determine the benefits of switching to didanosine compared with continuing zidovudine among patients infected with human immunodeficiency virus (HIV) who have previously used zidovudine and have signs of clinical deterioration. Design: Randomized, double-blind, two- armed, parallel, comparative clinical trial with a blinded, compassionate crossover provision at 12 weeks. Setting: Outpatient clinics at 19 tertiary care medical centers. Patients: 312 patients infected with HIV who had received zidovudine for 6 months or more, had CD4 cell counts of 300/mm3 or less, and had signs of clinical deterioration within 12 weeks before study entry. Intervention: Peroral didanosine tablets (600 mg/d adjusted for weight, 'high dose') or zidovudine capsules (600 mg/d). Measurements: Primary study end points were death, a new acquired immunodeficiency syndrome (AIDS)- defining event, or the combination of two new or recurrent HIV-related diagnoses with a 50% decrease in CD4 cells. Results: Switching to didanosine was associated with fewer end points than continuing zidovudine (relative risk [RR] for zidovudine:didanosine = 1.5; 95% Cl, 1.1 to 2.0). This benefit was consistent across subgroups of patients with either AIDS-related complex or AIDS and was most apparent among those with a CD4 count at entry of 100/mm3 or more (RR = 2.2; Cl, 1.1 to 4.4). Conclusions: This study shows a positive treatment effect for switching from zidovudine to didanosine among patients with either AIDS-related complex or AIDS and validates the common practice of using clinical signs or a decrease in the CD4 count as an indication for changing therapy.

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