Once-daily versus twice-daily lopinavir/ritonavir in antiretroviral-naive HIV-positive patients: a 48-week randomized clinical trial.
The safety, pharmacokinetics, and antiviral activity of lopinavir, a human immunodeficiency virus (HIV) protease inhibitor, coformulated with ritonavir as a pharmacokinetic enhancer were evaluated in 38 antiretroviral-naive patients randomized 1:1 to receive open-label lopinavir/ritonavir at a dose of 800/200 mg once daily or 400/100 mg twice daily, each in combination with stavudine and lamivudine twice daily, for 48 weeks. Over the course of 48 weeks, median predose concentrations of lopinavir exceeded the protein-binding corrected concentration required to inhibit replication of wild-type HIV by 50% in vitro by 40- and 84-fold in the once- and twice-daily groups, respectively. Predose concentrations of lopinavir were more variable in the once-daily group (mean +/- SD, 3.62+/-3.38 microg/mL for the once-daily group and 7.13+/-2.93 microg/mL for the twice-daily group). At week 48, in an intent-to-treat (missing = failure) analysis, 74% of patients in the once-daily group and 79% of patients in the twice-daily group had HIV RNA levels of <50 copies/mL (P=.70). Study drug-related discontinuations occurred in 1 patient in each treatment group. Genotypic resistance testing of 4 patients with HIV RNA levels >400 copies/mL between weeks 24 and 48 demonstrated no protease inhibitor-resistance mutations.
Eron
Joseph J
JJ
Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. jeron@med.unc.edu.
Feinberg
Judith
J
Kessler
Harold A
HA
Horowitz
Harold W
HW
Witt
Mallory D
MD
Carpio
Felix F
FF
Wheeler
David A
DA
Ruane
Peter
P
Mildvan
Donna
D
Yangco
Bienvenido G
BG
Bertz
Richard
R
Bernstein
Barry
B
King
Martin S
MS
Sun
Eugene
E
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir