Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovudine alone in HIV-1-infected antiretroviral-naive adults. Amprenavir PROAB3001 International Study Team.
OBJECTIVE
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, antiretroviral-naive subjects.


METHODS
Subjects (n=232) with a CD4 T cell count of > or =200 cells/mm3, plasma HIV-1 RNA levels of > or =10000 copies/ml, and < or =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 > or =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.
Goodgame
J C
JC
Central Florida Research Initiative, Altamonte Springs, Florida, USA.
Pottage
J C
JC
Jablonowski
H
H
Hardy
W D
WD
Stein
A
A
Fischl
M
M
Morrow
P
P
Feinberg
J
J
Brothers
C H
CH
Vafidis
I
I
Nacci
P
P
Yeo
J
J
Pedneault
L
L
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D019259:Lamivudine; D015215:Zidovudine; C095108:amprenavir