Exploratory study comparing the metabolic toxicities of a lopinavir/ritonavir plus saquinavir dual protease inhibitor regimen versus a lopinavir/ritonavir plus zidovudine/lamivudine nucleoside regimen.
OBJECTIVE
To assess the safety, efficacy and metabolic toxicity of lopinavir/ritonavir + saquinavir or zidovudine/lamivudine and evaluate the pharmacokinetics of lopinavir/ritonavir + saquinavir.


METHODS
HIV-1-infected, antiretroviral-naive subjects were randomized to lopinavir/ritonavir (400/100 mg) twice daily + saquinavir (800 mg) or zidovudine/lamivudine (150/300 mg) in a Phase II, 48 week study. Subjects receiving lopinavir/ritonavir + zidovudine/lamivudine initiated escalating doses of saquinavir (400, 600 and 800 mg) weekly for 3 weeks.


RESULTS
By intent-to-treat (non-completer = failure) analysis, 10/16 (63%) lopinavir/ritonavir + saquinavir-treated and 7/14 (50%) lopinavir/ritonavir + zidovudine/lamivudine-treated subjects achieved plasma HIV-1 RNA <50 copies/mL (P=0.713) at week 48. Safety, tolerability, metabolic changes and truncal fat increases were similar between groups. Small decreases in the lower extremity fat in the zidovudine/lamivudine group (-6%) and a statistically significant increase in the lower extremity fat in the saquinavir group (+19%) were observed. Lopinavir/ritonavir co-administered with saquinavir 600 or 800 mg twice daily produced saquinavir concentrations similar to those previously reported for saquinavir/ritonavir 1000/100 mg twice daily.


CONCLUSIONS
Treatment regimens had similar efficacy and tolerability. Metabolic parameters suggested lipoatrophy in the zidovudine/lamivudine treatment group. Saquinavir 600 and 800 mg twice daily produced concentrations similar to those previously reported for saquinavir/ritonavir 1000/100 mg twice daily.
Cameron
D William
DW
University of Ottawa at The Ottawa Hospital, Box 228, 501 Smyth Rd., Ottawa, ON, Canada, K1H 8L6.
Becker
Stephen
S
King
Martin S
MS
da Silva
Barbara
B
Klein
Cheri
C
Tokimoto
Debbie
D
Foit
Cheryl
C
Calhoun
Deborah
D
Bernstein
Barry
B
Hanna
George J
GJ
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D019258:Saquinavir / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019258:Saquinavir; D019438:Ritonavir