Similar virologic and immunologic efficacy with fosamprenavir boosted with 100 mg or 200 mg of ritonavir in HIV-infected patients: results of the LESS trial.
OBJECTIVE
ritonavir (RTV) effectively boosts most protease inhibitors but is associated with significant dose-dependent adverse events (AEs). In an effort to better manage toxicities through a reduced dose of RTV, this study compared fosamprenavir (FPV) boosted with RTV 100 mg (FPV/r100) or with RTV 200 mg (FPV/r200) daily.


METHODS
this 24-week, open-label study enrolled patients taking a FPV/r 200-containing regimen who had HIV RNA <400 copies/mL and randomized them 1:2 to continue that regimen or simplify to FPV/r100 once daily. Other medications were not altered. The primary endpoint was the percentage of patients without suspected or confirmed virologic failure (HIV RNA ≥ 400 copies/mL) through week 24 by a missing/discontinuation equals failure (M/D=F) analysis. Noninferiority criteria were demonstrated if the lower bound of the 95% confidence interval (CI) for the difference in the primary endpoint rates between groups was greater than -12.


RESULTS
the 2 regimens met prespecified noninferiority criteria (FPV/r100, 92%; FPV/r 200, 94%; 95% CI, -9.36 to 5.12). At week 24, the percentage of patients with HIV RNA <50 copies/mL by M/ D=F was 83% in the FPV/r100 group and 85% in the FPV/r 200 group. Drug-related grade 2-4 AEs were uncommon (FPV/r100, 4%; FPV/r 200, 7%). Median changes in lipids were similar in both groups, with the exception of triglycerides (FPV/r100, -21 mg/dL; FPV/r 200, -2 mg/dL).


CONCLUSIONS
this 24-week study demonstrated that among previously suppressed patients, once-daily FPV/r100 was similar to FPV/r 200 in virologic and immunologic effects but was associated with greater decreases from baseline in triglyceride levels.
Community Research Initiative of New England, Boston, Massachusetts, USA.
Calvin
C
Cohen
Edwin
E
Dejesus
Anthony
A
Lamarca
Benjamin
B
Young
Linda
L
Yau
Lisa
L
Patel
Cindy
C
Vavro
Mary Beth
MB
Wire
Paul
P
Wannamaker
Mark
M
Shaefer
D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D010755:Organophosphates; D012367:RNA, Viral; D013449:Sulfonamides; D014280:Triglycerides; D002784:Cholesterol; D019438:Ritonavir; C426859:fosamprenavir