Antiretroviral effect and safety of abacavir alone and in combination with zidovudine in HIV-infected adults

Saag, Michael S.; Sönnerborg, Anders; Torres, Ramón A.; Lancaster, Danny J.; Gazzard, Brian; Schooley, Robert T.; Romero, Carmen; Kelleher, Dennis; Spreen, William; LaFon, Stephen W.

doi:10.1097/00002030-199816000-00002

Cited by 85 publications

(64 citation statements)

References 9 publications

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“…As evidenced by the ITT switch-included analysis, the response rate for the 3TC/ZDV group was comparable to that of the of the ABC/3TC/ZDV group at week 48, indicating that an appropriate use of ABC in this population would be as an alternative nucleoside analog in salvage regimens. The potency of ABC, as demonstrated in other studies [31][32][33][34] and as indicated by the additional viral suppression achieved in the present study, suggest that ABC can be combined successfully with protease inhibitors and other antiretroviral agents in a salvage regimen.…”

Section: Discussionsupporting

confidence: 84%

“…The frequency of ABC-related hypersensitivity reaction in this study was 3%, consistent with the incidence reported in other studies. 31,33 Incidences of grades 3 and 4 hepatic, hematologic, pancreatic, and renal toxicities occurred infrequently among participants treated with ABC/3TC/ZDV and were no higher than incidences observed among participants treated with 3TC/ZDV. These tolerability/safety findings are in agreement with those reported previously in other clinical trials that have evaluated ABC/3TC/ZDV 31,33,34 or 3TC/ZDV.…”

Section: Discussionmentioning

confidence: 89%

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A Randomized, Double-Blind Study of Triple Nucleoside Therapy of Abacavir, Lamivudine, and Zidovudine Versus Lamivudine and Zidovudine in Previously Treated Human Immunodeficiency Virus Type 1-Infected Children

et al. 2001

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ABSTRACT. Objectives. Abacavir (ABC) is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. We compared the efficacy, safety, and tolerability of combination therapy with ABC, lamivudine (3TC), and zidovudine (ZDV) versus 3TC and ZDV in antiretroviral experienced HIV-1-infected children over 48 weeks.Methods. Two hundred five HIV-1-infected children who had received previous antiretroviral therapy and had CD4 ؉ cell counts >100 cells/mm 3 were stratified by age and by previous treatment. Participants were randomly assigned to receive ABC (8 mg/kg twice daily [BID]) plus 3TC (4 mg/kg BID) and ZDV (180 mg/m 2 BID; ABC/3TC/ZDV group) or ABC placebo plus 3TC (4 mg/kg BID) and ZDV (180 mg/m 2 ; 3TC/ZDV group). Participants who met a protocol-defined switch criteria (plasma HIV-1 RNA >0.5 log 10 copies/mL above baseline at week 8 or >10 000 copies/mL after week 16) had the option to switch to open-label ABC plus any antiretroviral combination or continue randomized therapy or withdraw from the study.Results. The Kaplan-Meier estimates (95% confidence interval) of the proportion of participants who maintained HIV-1 RNA levels <10 000 copies/mL for 48 weeks or more was significantly better in the ABC/3TC/ ZDV group compared with the 3TC/ZDV group: 33% (23%-42%) versus 21% (13%-29%). At week 48, the proportions of participants with HIV-1 RNA <10 000 copies/mL were 36% versus 26% for the ABC/3TC/ZDV and 3TC/ZDV groups, respectively, by intent-to-treat analysis. For the subgroup of participants with baseline HIV-1 RNA >10 000 copies/mL, a significantly higher proportion of participants in the ABC/3TC/ZDV group had HIV-1 RNA <10 000 copies/mL compared with the 3TC/ ZDV group (29% vs 12%) but no difference was observed in the subgroup of participants with baseline HIV-1 RNA <10 000 copies/mL (78% vs 72%). The median changes from baseline in CD4 ؉ cell counts were greater in the ABC/3TC/ZDV group than in the 3TC/ZDV group. Few participants (3%) experienced abacavir-related hypersensitivity reaction.Conclusions. ABC, in combination with 3TC and ZDV, provides additional antiretroviral activity over 48 weeks, compared with combination therapy with 3TC and ZDV in antiretroviral experienced HIV-1-infected children. ABC was safe and generally well-tolerated and should be considered an active component of combination antiretroviral therapy in this pediatric population. ABBREVIATIONS. HIV-1, human immunodeficiency virus type 1; RT, reverse transcriptase; ZDV, zidovudine; ddI, didanosine; 3TC, lamivudine; ABC, abacavir; BID, twice daily; ITT, intent-to-treat; AAUCMB, average area under the curve minus baseline; NAUC, normalized area under the curve; NRTI, nucleoside reverse transcriptase inhibitors.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 89%

A Randomized, Double-Blind Study of Triple Nucleoside Therapy of Abacavir, Lamivudine, and Zidovudine Versus Lamivudine and Zidovudine in Previously Treated Human Immunodeficiency Virus Type 1-Infected Children

et al. 2001

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“…The objective of the present study (Glaxo Wellcome protocol CNAA-2001) was to determine the multiple-dose pharmacokinetics and pharmacodynamics of abacavir in HIV-1-infected subjects following oral administration of daily doses that ranged from 600 to 1,800 mg, with and without zidovudine (ZDV). The clinical efficacy and safety results of this study have been reported elsewhere (11).…”

mentioning

confidence: 76%

“…Details about the study population and design have been reported elsewhere (11) and are summarized here. Sixty-eight male subjects and 11 female subjects who were Ն13 years of age, who were confirmed to have HIV-1 infection, and who had CD4 ϩ counts of 200 to 550 cells/mm 3 were enrolled in the study at 1 of 13 study centers in the United States and Europe.…”

Section: Methodsmentioning

confidence: 99%

“…The main route of abacavir elimination is metabolism to the 5Ј-carboxylate and the 5Ј-glucuronide metabolites, and 83% of a radiolabeled oral dose is recovered in urine, with less than 2% recovered unchanged in the urine (10). Clinical studies have reported that abacavir produced marked decreases in plasma HIV-1 RNA levels and concomitant increases in CD4 ϩ -cell counts when administered alone or in combination with other NRTIs or protease inhibitors (11,13 Abacavir has demonstrated few drug interactions in patients. No clinically significant pharmacokinetic interactions were found between abacavir and zidovudine (16), lamivudine (16), or amprenavir (J.…”

mentioning

confidence: 99%

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Multiple-Dose Pharmacokinetics and Pharmacodynamics of Abacavir Alone and in Combination with Zidovudine in Human Immunodeficiency Virus-Infected Adults

McDowell

Lou²,

Symonds

et al. 2000

Antimicrob Agents Chemother

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Abacavir (1592U89) is a nucleoside reverse transcriptase inhibitor with potent activity against human immunodeficiency virus type 1 (HIV-1) when used alone or in combination with other antiretroviral agents. The present study was conducted to determine the multiple-dose pharmacokinetics and pharmacodynamics of abacavir in HIV-1-infected subjects following oral administration of daily doses that ranged from 600 to 1,800 mg, with and without zidovudine. Seventy-nine subjects received abacavir monotherapy for 4 weeks ( At the clinical abacavir dose (300 mg BID) zidovudine coadministration had no effect on the abacavir AUC tau , which is most closely associated with efficacy. Zidovudine pharmacokinetics appeared to be unaffected by abacavir. Statistically significant but weak relationships were found for the change in the log 10 HIV-1 RNA load from the baseline to week 4 versus total daily AUC tau and C tau (P < 0.05). The incidence of nausea was significantly associated with total daily AUC tau and C max . In conclusion, abacavir has predictable pharmacokinetic characteristics following the administration of multiple doses.

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Abacavir-Lamivudine-Zidovudine vs Indinavir-Lamivudine-Zidovudine in Antiretroviral-Naive HIV-Infected Adults<SUBTITLE>A Randomized Equivalence Trial</SUBTITLE>

Staszewski¹

2001

JAMA

260

141

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Antiretroviral effect and safety of abacavir alone and in combination with zidovudine in HIV-infected adults

Abstract: In HIV-infected subjects who have received little or no prior antiretroviral therapy, treatment with abacavir alone or in combination with ZDV is well tolerated and resulted in sustained improvements in key immunologic and virologic efficacy parameters through 12 weeks.

Cited by 85 publications

References 9 publications

A Randomized, Double-Blind Study of Triple Nucleoside Therapy of Abacavir, Lamivudine, and Zidovudine Versus Lamivudine and Zidovudine in Previously Treated Human Immunodeficiency Virus Type 1-Infected Children

A Randomized, Double-Blind Study of Triple Nucleoside Therapy of Abacavir, Lamivudine, and Zidovudine Versus Lamivudine and Zidovudine in Previously Treated Human Immunodeficiency Virus Type 1-Infected Children

Multiple-Dose Pharmacokinetics and Pharmacodynamics of Abacavir Alone and in Combination with Zidovudine in Human Immunodeficiency Virus-Infected Adults

Abacavir-Lamivudine-Zidovudine vs Indinavir-Lamivudine-Zidovudine in Antiretroviral-Naive HIV-Infected Adults<SUBTITLE>A Randomized Equivalence Trial</SUBTITLE>

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