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 language | English |
|---|---|
| Pages (from-to) | 215-225 |
| Number of pages | 11 |
| Journal | Antiviral Therapy |
| Volume | 5 |
| Issue number | 3 |
| State | Published - Nov 22 2000 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
Cite this
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 journal › Article
}
TY - JOUR
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.
PY - 2000/11/22
Y1 - 2000/11/22
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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M3 - Article
VL - 5
SP - 215
EP - 225
JO - Antiviral Therapy
JF - Antiviral Therapy
SN - 1359-6535
IS - 3
ER -