The long-term pharmacokinetics and safety of adding low-dose ritonavir to a nelfinavir 1,250 mg twice-daily regimen in HIV-infected patients.
OBJECTIVE
To evaluate the long-term pharmacokinetics and safety of adding ritonavir 100 mg twice-daily to a nelfinavir 1250 mg twice-daily regimen in HIV-infected patients.


METHODS
This was a prospective, randomized, open-label, controlled 24-week study. Sixteen patients receiving a nelfinavir 1250 mg twice-daily regimen with plasma viral load <1000 HIV-1 RNA copies/mL were randomized to continue treatment or to have ritonavir 100 mg twice-daily added. Safety, including fasting lipid levels, was evaluated at weeks 4, 12 and 24. Patients who were randomized to have ritonavir added (n=9) participated in three 12-h pharmacokinetic evaluations at baseline, week 4 and week 24.


RESULTS
Increases in median nelfinavir steady-state plasma concentrations at 12 h (C(12)) from 512 to 773 ng/mL [median difference 450 ng/mL; 95% confidence interval (CI) 116--1510 ng/mL] and in median active nelfinavir metabolite M 8 C(12) from 107 to 603 ng/mL (median difference 545 ng/mL; 95% CI 370--891) were seen after the addition of low-dose ritonavir (baseline to week 24). There were no differences between the nelfinavir or M 8 pharmacokinetic parameters at weeks 4 and 24. No significant changes or differences in the concentration of fasting total cholesterol, low-density lipoprotein (LDL) cholesterol or total triglycerides or in the occurrence of adverse events were observed within or between the two groups.


CONCLUSIONS
Nelfinavir and especially M 8 concentrations are increased when low-dose ritonavir is added to a nelfinavir-containing regimen. The combination seems to be safe and the nelfinavir/ritonavir regimen could be an option in patients with low nelfinavir+M 8 concentrations.
Justesen
U S
US
Department of Infectious Diseases, Odense University Hospital, Odense, Denmark. ujustesen@health.sdu.dk
Hansen
I M
IM
Andersen
A B
AB
Klitgaard
N A
NA
Black
F T
FT
Gerstoft
J
J
Mathiesen
L R
LR
Pedersen
C
C
D000328:Adult; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D011446:Prospective Studies; D019438:Ritonavir / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D019562:Viral Load
D017320:HIV Protease Inhibitors; D008055:Lipids; D019888:Nelfinavir; D019438:Ritonavir