Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovudine alone in HIV-1-infected antiretroviral-naive adults

J. C. Goodgame, Jr Pottage J.C., H. Jablonowski, W. D. Hardy, A. Stein, Margaret A Fischl, P. Morrow, J. Feinberg, C. H. Brothers, I. Vafidis, P. Nacci, J. Yeo, L. Pedneault

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Objectives: To compare the antiviral activity and safety of a new protease inhibitor, amprenavir (141W94) in combination with lamivudine and zidovudine, versus lamivudine and zidovudine alone in HIV-1 infected, antiretroviralnaive subjects. Design: Subjects (n=232) with a CD4 T cell count of ≥200 cells/mm3, plasma HIV-1 RNA levels of ≥10000 copies/ml, and ≤4 weeks of prior nucleoside antiretroviral therapy, were stratified according to baseline plasma HIV-1 RNA level (10000-30000; 30000-100000; or >100000 copies/ml). Subjects received double-blind treatment with either 1200 mg amprenavir twice daily in combination with lamivudine (150 mg twice daily) and zidovudine (300 mg twice daily) (amprenavir/lamivudine/zidovudine) or matched placebo, lamivudine and zidovudine for 16 weeks. Thereafter, subjects with confirmed plasma HIV-1 RNA levels of ≥400 copies/ml could add open-label amprenavir or switch to other antiretrovirals and continue treatment for up to a minimum of 48 weeks. The primary endpoint of the study was defined as the proportion of subjects with plasma HIV-1 RNA of <400 copies/ml at 48 weeks. Results: At 48 weeks, a significantly greater proportion of amprenavir/lamivudine/zidovudine subjects had plasma HIV-1 RNA levels <400 copies/ml than lamivudine/zidovudine subjects in the overall population: 41 versus 3% (intent-to-treat missing equals failure analysis) (P<0.001); 93 versus 42% (as-treated analysis) (P<0.001); and within each of the three randomization strata (P<0.001). Subjects on amprenavir/lamivudine/zidovudine experienced longer time to event (permanent discontinuation of randomized therapy or viral rebound) than those on lamivudine/zidovudine (median of 33 versus 13 weeks; P<0.001). A significantly greater incidence of drug-related nausea, vomiting, rash and oral/perioral paresthesia was observed with amprenavir/lamivudine/zidovudine than with lamivudine/zidovudine. Conclusions: Amprenavir, in combination with lamivudine and zidovudine, has potent and durable antiviral activity in antiretroviral-naive subjects over 48 weeks. Amprenavir was safe and generally well tolerated.

Original languageEnglish
Pages (from-to)215-225
Number of pages11
JournalAntiviral Therapy
Volume5
Issue number3
StatePublished - Nov 22 2000
Externally publishedYes

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Lamivudine
Zidovudine
HIV-1
RNA
Antiviral Agents
amprenavir
Paresthesia
Therapeutics
CD4 Lymphocyte Count
Random Allocation
Plasma Cells
Exanthema
Protease Inhibitors
Nucleosides
Nausea
Vomiting
Placebos

ASJC Scopus subject areas

  • Pharmacology

Cite this

Goodgame, J. C., Pottage J.C., J., Jablonowski, H., Hardy, W. D., Stein, A., Fischl, M. A., ... Pedneault, L. (2000). Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovudine alone in HIV-1-infected antiretroviral-naive adults. Antiviral Therapy, 5(3), 215-225.

Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovudine alone in HIV-1-infected antiretroviral-naive adults. / Goodgame, J. C.; Pottage J.C., Jr; Jablonowski, H.; Hardy, W. D.; Stein, A.; Fischl, Margaret A; Morrow, P.; Feinberg, J.; Brothers, C. H.; Vafidis, I.; Nacci, P.; Yeo, J.; Pedneault, L.

In: Antiviral Therapy, Vol. 5, No. 3, 22.11.2000, p. 215-225.

Research output: Contribution to journalArticle

Goodgame, JC, Pottage J.C., J, Jablonowski, H, Hardy, WD, Stein, A, Fischl, MA, Morrow, P, Feinberg, J, Brothers, CH, Vafidis, I, Nacci, P, Yeo, J & Pedneault, L 2000, 'Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovudine alone in HIV-1-infected antiretroviral-naive adults', Antiviral Therapy, vol. 5, no. 3, pp. 215-225.
Goodgame, J. C. ; Pottage J.C., Jr ; Jablonowski, H. ; Hardy, W. D. ; Stein, A. ; Fischl, Margaret A ; Morrow, P. ; Feinberg, J. ; Brothers, C. H. ; Vafidis, I. ; Nacci, P. ; Yeo, J. ; Pedneault, L. / Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovudine alone in HIV-1-infected antiretroviral-naive adults. In: Antiviral Therapy. 2000 ; Vol. 5, No. 3. pp. 215-225.
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abstract = "Objectives: To compare the antiviral activity and safety of a new protease inhibitor, amprenavir (141W94) in combination with lamivudine and zidovudine, versus lamivudine and zidovudine alone in HIV-1 infected, antiretroviralnaive subjects. Design: Subjects (n=232) with a CD4 T cell count of ≥200 cells/mm3, plasma HIV-1 RNA levels of ≥10000 copies/ml, and ≤4 weeks of prior nucleoside antiretroviral therapy, were stratified according to baseline plasma HIV-1 RNA level (10000-30000; 30000-100000; or >100000 copies/ml). Subjects received double-blind treatment with either 1200 mg amprenavir twice daily in combination with lamivudine (150 mg twice daily) and zidovudine (300 mg twice daily) (amprenavir/lamivudine/zidovudine) or matched placebo, lamivudine and zidovudine for 16 weeks. Thereafter, subjects with confirmed plasma HIV-1 RNA levels of ≥400 copies/ml could add open-label amprenavir or switch to other antiretrovirals and continue treatment for up to a minimum of 48 weeks. The primary endpoint of the study was defined as the proportion of subjects with plasma HIV-1 RNA of <400 copies/ml at 48 weeks. Results: At 48 weeks, a significantly greater proportion of amprenavir/lamivudine/zidovudine subjects had plasma HIV-1 RNA levels <400 copies/ml than lamivudine/zidovudine subjects in the overall population: 41 versus 3{\%} (intent-to-treat missing equals failure analysis) (P<0.001); 93 versus 42{\%} (as-treated analysis) (P<0.001); and within each of the three randomization strata (P<0.001). Subjects on amprenavir/lamivudine/zidovudine experienced longer time to event (permanent discontinuation of randomized therapy or viral rebound) than those on lamivudine/zidovudine (median of 33 versus 13 weeks; P<0.001). A significantly greater incidence of drug-related nausea, vomiting, rash and oral/perioral paresthesia was observed with amprenavir/lamivudine/zidovudine than with lamivudine/zidovudine. Conclusions: Amprenavir, in combination with lamivudine and zidovudine, has potent and durable antiviral activity in antiretroviral-naive subjects over 48 weeks. Amprenavir was safe and generally well tolerated.",
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T1 - Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovudine alone in HIV-1-infected antiretroviral-naive adults

AU - Goodgame, J. C.

AU - Pottage J.C., Jr

AU - Jablonowski, H.

AU - Hardy, W. D.

AU - Stein, A.

AU - Fischl, Margaret A

AU - Morrow, P.

AU - Feinberg, J.

AU - Brothers, C. H.

AU - Vafidis, I.

AU - Nacci, P.

AU - Yeo, J.

AU - Pedneault, L.

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N2 - Objectives: To compare the antiviral activity and safety of a new protease inhibitor, amprenavir (141W94) in combination with lamivudine and zidovudine, versus lamivudine and zidovudine alone in HIV-1 infected, antiretroviralnaive subjects. Design: Subjects (n=232) with a CD4 T cell count of ≥200 cells/mm3, plasma HIV-1 RNA levels of ≥10000 copies/ml, and ≤4 weeks of prior nucleoside antiretroviral therapy, were stratified according to baseline plasma HIV-1 RNA level (10000-30000; 30000-100000; or >100000 copies/ml). Subjects received double-blind treatment with either 1200 mg amprenavir twice daily in combination with lamivudine (150 mg twice daily) and zidovudine (300 mg twice daily) (amprenavir/lamivudine/zidovudine) or matched placebo, lamivudine and zidovudine for 16 weeks. Thereafter, subjects with confirmed plasma HIV-1 RNA levels of ≥400 copies/ml could add open-label amprenavir or switch to other antiretrovirals and continue treatment for up to a minimum of 48 weeks. The primary endpoint of the study was defined as the proportion of subjects with plasma HIV-1 RNA of <400 copies/ml at 48 weeks. Results: At 48 weeks, a significantly greater proportion of amprenavir/lamivudine/zidovudine subjects had plasma HIV-1 RNA levels <400 copies/ml than lamivudine/zidovudine subjects in the overall population: 41 versus 3% (intent-to-treat missing equals failure analysis) (P<0.001); 93 versus 42% (as-treated analysis) (P<0.001); and within each of the three randomization strata (P<0.001). Subjects on amprenavir/lamivudine/zidovudine experienced longer time to event (permanent discontinuation of randomized therapy or viral rebound) than those on lamivudine/zidovudine (median of 33 versus 13 weeks; P<0.001). A significantly greater incidence of drug-related nausea, vomiting, rash and oral/perioral paresthesia was observed with amprenavir/lamivudine/zidovudine than with lamivudine/zidovudine. Conclusions: Amprenavir, in combination with lamivudine and zidovudine, has potent and durable antiviral activity in antiretroviral-naive subjects over 48 weeks. Amprenavir was safe and generally well tolerated.

AB - Objectives: To compare the antiviral activity and safety of a new protease inhibitor, amprenavir (141W94) in combination with lamivudine and zidovudine, versus lamivudine and zidovudine alone in HIV-1 infected, antiretroviralnaive subjects. Design: Subjects (n=232) with a CD4 T cell count of ≥200 cells/mm3, plasma HIV-1 RNA levels of ≥10000 copies/ml, and ≤4 weeks of prior nucleoside antiretroviral therapy, were stratified according to baseline plasma HIV-1 RNA level (10000-30000; 30000-100000; or >100000 copies/ml). Subjects received double-blind treatment with either 1200 mg amprenavir twice daily in combination with lamivudine (150 mg twice daily) and zidovudine (300 mg twice daily) (amprenavir/lamivudine/zidovudine) or matched placebo, lamivudine and zidovudine for 16 weeks. Thereafter, subjects with confirmed plasma HIV-1 RNA levels of ≥400 copies/ml could add open-label amprenavir or switch to other antiretrovirals and continue treatment for up to a minimum of 48 weeks. The primary endpoint of the study was defined as the proportion of subjects with plasma HIV-1 RNA of <400 copies/ml at 48 weeks. Results: At 48 weeks, a significantly greater proportion of amprenavir/lamivudine/zidovudine subjects had plasma HIV-1 RNA levels <400 copies/ml than lamivudine/zidovudine subjects in the overall population: 41 versus 3% (intent-to-treat missing equals failure analysis) (P<0.001); 93 versus 42% (as-treated analysis) (P<0.001); and within each of the three randomization strata (P<0.001). Subjects on amprenavir/lamivudine/zidovudine experienced longer time to event (permanent discontinuation of randomized therapy or viral rebound) than those on lamivudine/zidovudine (median of 33 versus 13 weeks; P<0.001). A significantly greater incidence of drug-related nausea, vomiting, rash and oral/perioral paresthesia was observed with amprenavir/lamivudine/zidovudine than with lamivudine/zidovudine. Conclusions: Amprenavir, in combination with lamivudine and zidovudine, has potent and durable antiviral activity in antiretroviral-naive subjects over 48 weeks. Amprenavir was safe and generally well tolerated.

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