Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex

Gail Skowron, Samuel A. Bozzette, Lynette Lim, Carla B. Pettinelli, Herbert H. Schaumburg, Joseph C. Arezzo, Margaret A. Fischl, William G. Powderly, David J. Gocke, Douglas D. Richman, John C. Pottage, Diana Antoniskis, George F. McKinley, Newton E. Hyslop, Graham Ray, Gary Simon, Nancy Reed, Marsha L. LoFaro, Raj B. Uttamchandani, Lawrence D. Gelb & 10 others Steven J. Sperber, Robert L. Murphy, John M. Leedom, Michael H. Grieco, James Zachary, Martin S. Hirsch, Stephen A. Spector, Joseph Bigley, Whaijen Soo, Thomas C. Merigan

Research output: Contribution to journalArticle

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Abstract

Objective: To determine whether alternating regimens consisting of zidovudine and 2′,3′-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. Design: An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. Setting: Outpatient clinics of 12 AIDS Clinical Trials Units. Patients: One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigertemia (≥70 pg/mL). Intervention: Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. Measurements: Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). Results: Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P<0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high fates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. Conclusions: These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.

Original languageEnglish (US)
Pages (from-to)321-330
Number of pages10
JournalAnnals of Internal Medicine
Volume118
Issue number5
StatePublished - Mar 1 1993
Externally publishedYes

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Zalcitabine
Zidovudine
Acquired Immunodeficiency Syndrome
Therapeutics
Extremities
CD4 Lymphocyte Count
Antigens
Phase II Clinical Trials
Peripheral Nervous System Diseases
Ambulatory Care Facilities
Serum
Pharmaceutical Preparations
Weight Gain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Skowron, G., Bozzette, S. A., Lim, L., Pettinelli, C. B., Schaumburg, H. H., Arezzo, J. C., ... Merigan, T. C. (1993). Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex. Annals of Internal Medicine, 118(5), 321-330.

Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex. / Skowron, Gail; Bozzette, Samuel A.; Lim, Lynette; Pettinelli, Carla B.; Schaumburg, Herbert H.; Arezzo, Joseph C.; Fischl, Margaret A.; Powderly, William G.; Gocke, David J.; Richman, Douglas D.; Pottage, John C.; Antoniskis, Diana; McKinley, George F.; Hyslop, Newton E.; Ray, Graham; Simon, Gary; Reed, Nancy; LoFaro, Marsha L.; Uttamchandani, Raj B.; Gelb, Lawrence D.; Sperber, Steven J.; Murphy, Robert L.; Leedom, John M.; Grieco, Michael H.; Zachary, James; Hirsch, Martin S.; Spector, Stephen A.; Bigley, Joseph; Soo, Whaijen; Merigan, Thomas C.

In: Annals of Internal Medicine, Vol. 118, No. 5, 01.03.1993, p. 321-330.

Research output: Contribution to journalArticle

Skowron, G, Bozzette, SA, Lim, L, Pettinelli, CB, Schaumburg, HH, Arezzo, JC, Fischl, MA, Powderly, WG, Gocke, DJ, Richman, DD, Pottage, JC, Antoniskis, D, McKinley, GF, Hyslop, NE, Ray, G, Simon, G, Reed, N, LoFaro, ML, Uttamchandani, RB, Gelb, LD, Sperber, SJ, Murphy, RL, Leedom, JM, Grieco, MH, Zachary, J, Hirsch, MS, Spector, SA, Bigley, J, Soo, W & Merigan, TC 1993, 'Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex', Annals of Internal Medicine, vol. 118, no. 5, pp. 321-330.
Skowron, Gail ; Bozzette, Samuel A. ; Lim, Lynette ; Pettinelli, Carla B. ; Schaumburg, Herbert H. ; Arezzo, Joseph C. ; Fischl, Margaret A. ; Powderly, William G. ; Gocke, David J. ; Richman, Douglas D. ; Pottage, John C. ; Antoniskis, Diana ; McKinley, George F. ; Hyslop, Newton E. ; Ray, Graham ; Simon, Gary ; Reed, Nancy ; LoFaro, Marsha L. ; Uttamchandani, Raj B. ; Gelb, Lawrence D. ; Sperber, Steven J. ; Murphy, Robert L. ; Leedom, John M. ; Grieco, Michael H. ; Zachary, James ; Hirsch, Martin S. ; Spector, Stephen A. ; Bigley, Joseph ; Soo, Whaijen ; Merigan, Thomas C. / Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex. In: Annals of Internal Medicine. 1993 ; Vol. 118, No. 5. pp. 321-330.
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abstract = "Objective: To determine whether alternating regimens consisting of zidovudine and 2′,3′-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. Design: An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. Setting: Outpatient clinics of 12 AIDS Clinical Trials Units. Patients: One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigertemia (≥70 pg/mL). Intervention: Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. Measurements: Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). Results: Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11{\%} to 15{\%}) or every other month (11{\%} to 14{\%}) than in those who received continuous zidovudine therapy (33{\%}) (P<0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high fates of peripheral neuropathy (41{\%} and 50{\%}, respectively). Neuropathy occurred in 10{\%} to 21{\%} of patients in the other three alternating-therapy limbs and in 17{\%} of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. Conclusions: These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.",
author = "Gail Skowron and Bozzette, {Samuel A.} and Lynette Lim and Pettinelli, {Carla B.} and Schaumburg, {Herbert H.} and Arezzo, {Joseph C.} and Fischl, {Margaret A.} and Powderly, {William G.} and Gocke, {David J.} and Richman, {Douglas D.} and Pottage, {John C.} and Diana Antoniskis and McKinley, {George F.} and Hyslop, {Newton E.} and Graham Ray and Gary Simon and Nancy Reed and LoFaro, {Marsha L.} and Uttamchandani, {Raj B.} and Gelb, {Lawrence D.} and Sperber, {Steven J.} and Murphy, {Robert L.} and Leedom, {John M.} and Grieco, {Michael H.} and James Zachary and Hirsch, {Martin S.} and Spector, {Stephen A.} and Joseph Bigley and Whaijen Soo and Merigan, {Thomas C.}",
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T1 - Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex

AU - Skowron, Gail

AU - Bozzette, Samuel A.

AU - Lim, Lynette

AU - Pettinelli, Carla B.

AU - Schaumburg, Herbert H.

AU - Arezzo, Joseph C.

AU - Fischl, Margaret A.

AU - Powderly, William G.

AU - Gocke, David J.

AU - Richman, Douglas D.

AU - Pottage, John C.

AU - Antoniskis, Diana

AU - McKinley, George F.

AU - Hyslop, Newton E.

AU - Ray, Graham

AU - Simon, Gary

AU - Reed, Nancy

AU - LoFaro, Marsha L.

AU - Uttamchandani, Raj B.

AU - Gelb, Lawrence D.

AU - Sperber, Steven J.

AU - Murphy, Robert L.

AU - Leedom, John M.

AU - Grieco, Michael H.

AU - Zachary, James

AU - Hirsch, Martin S.

AU - Spector, Stephen A.

AU - Bigley, Joseph

AU - Soo, Whaijen

AU - Merigan, Thomas C.

PY - 1993/3/1

Y1 - 1993/3/1

N2 - Objective: To determine whether alternating regimens consisting of zidovudine and 2′,3′-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. Design: An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. Setting: Outpatient clinics of 12 AIDS Clinical Trials Units. Patients: One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigertemia (≥70 pg/mL). Intervention: Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. Measurements: Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). Results: Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P<0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high fates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. Conclusions: These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.

AB - Objective: To determine whether alternating regimens consisting of zidovudine and 2′,3′-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. Design: An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. Setting: Outpatient clinics of 12 AIDS Clinical Trials Units. Patients: One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigertemia (≥70 pg/mL). Intervention: Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. Measurements: Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). Results: Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P<0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high fates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. Conclusions: These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.

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