A once-daily lopinavir/ritonavir-based regimen is noninferior to twice-daily dosing and results in similar safety and tolerability in antiretroviral-naive subjects through 48 weeks.
BACKGROUND
Lopinavir/ritonavir (LPV/r)-dosed twice daily has demonstrated durable efficacy in antiretroviral-naive and protease inhibitor (PI) -experienced patients. Study M05-730 compared LPV/r tablets dosed once daily vs. twice daily in antiretroviral-naive subjects.


METHODS
Six hundred sixty-four subjects were randomized to LPV/r soft gel capsules (SGCs) once daily, SGC twice daily, tablets once daily, and tablets twice daily, all with tenofovir and emtricitabine once daily. At week 8, all SGC-treated subjects were switched to tablets, maintaining randomized dose frequency. The primary efficacy analysis used an intent-to-treat, noncompleter = failure approach to assess noninferiority of the LPV/r once-daily group compared with the twice-daily group.


RESULTS
At week 48, 77% of once-daily-dosed subjects vs. 76% of twice-daily-dosed subjects had HIV-1 RNA <50 copies per milliliter (P = 0.715; 95% confidence interval for difference: 5% to 8%). Response rates were numerically similar between the once-daily and twice-daily groups among subjects with baseline HIV-1 RNA > or = 100,000 copies per milliliter (75% once daily vs. 74.6% twice daily; P > 0.999) or when analyzed by baseline CD4+ T-cell count (<50, 50 to <200, and > or = 200 cells/mm3). Rates of discontinuation and adverse events, including diarrhea, were similar between arms. Among subjects with protocol-defined virologic rebound through week 48, no new PI resistance mutations were detected.


CONCLUSIONS
At 48 weeks, the antiviral response in the LPV/r once-daily group was noninferior to the twice-daily group when coadministered with tenofovir and emtricitabine in antiretroviral-naive subjects. Efficacy was comparable between the once-daily and twice-daily groups regardless of baseline HIV-1 RNA or CD4+ T-cell count. Safety and tolerability of once-daily and twice-daily dosing was also comparable. No new PI resistance mutations were detected upon virologic rebound.
Gathe
Joseph
J
Therapeutic Concepts, Houston, TX, USA.
da Silva
Barbara A
BA
Cohen
Daniel E
DE
Loutfy
Mona R
MR
Podzamczer
Daniel
D
Rubio
Rafael
R
Gibbs
Sara
S
Marsh
Theresa
T
Naylor
Christian
C
Fredrick
Linda
L
Bernstein
Barry
B
D000328:Adult; D002214:Capsules; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013607:Tablets
D002214:Capsules; D011744:Pyrimidinones; D013607:Tablets; D061466:Lopinavir; D019438:Ritonavir