Jc. Goodgame et al., Amprenavir in combination with lamivudine and zidovudine versus lamivudineand zidovudine alone in HIV-1-infected antiretroviral-naive adults, ANTIVIR TH, 5(3), 2000, pp. 215-225
Objectives: To compare the antiviral activity and safety of a new protease
inhibitor, amprenavir (141W94) in combination with lamivudine and zidovudin
e, versus lamivudine and zidovudine alone in HIV-1 infected, antiretroviral
-naive subjects.
Design: Subjects (n-232) with a CD4 T cell count of greater than or equal t
o 200 cells/mm(3), plasma HIV-1 RNA levels of greater than or equal to 1000
0 copies/ml, and less than or equal to4 weeks of prior nucleoside antiretro
viral therapy, were stratified according to baseline plasma HIV-1 RNA level
(10000-30000; 30000-100000; or >100000 copies/ml), Subjects received doubl
e-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 zidovu
dine for 10 weeks. Thereafter, subjects with confirmed plasma HIV-1 RNA lev
els of greater than or equal to 400 copies/ml could add open-label amprenav
ir or switch to other antiretrovirals and continue treatment for up to a mi
nimum of 48 weeks. The primary endpoint of the study was defined as the pro
portion of subjects with plasma HIV-1 RNA of <400 copies/ml at 48 weeks. Re
sults: At 48 weeks, a significantly greater proportion of amprenavir/lamivu
dine/zidovudine subjects had plasma HIV-1 RNA levels <400 copies/ml than la
mivudine/zidovudine subjects in the overall population: 41 versus 3% (inten
t-to-treat missing equals failure analysis) (P<0.001); 93 versus 42% (as-tr
eated analysis) (P<0.001); and within each of the three randomization strat
a (P<0.001), Subjects on amprenavir/lamivudine/zidovudine experienced longe
r time to event (permanent discontinuation of randomized therapy or viral r
ebound) than those on lamivudine/zidovudine (median of 33 versus 13 weeks;
P<0.001). A significantly greater incidence of drug-related nausea, vomitin
g, rash and oral/perioral paresthesia was observed with amprenavir/lamivudi
ne/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.