A lopinavir/ritonavir-based once-daily regimen results in better compliance and is non-inferior to a twice-daily regimen through 96 weeks.
We assessed the safety and efficacy and evaluated the adherence to lopinavir/ritonavir (LPV/r) dosed QD or BID in antiretroviral-naive, HIV-1-infected subjects through 96 weeks of treatment. A randomized, open-label, multicenter comparative study was conducted. A total of 190 antiretroviral-naive subjects with plasma HIV-1 RNA above 1000 copies/ml and any CD4(+) T cell count were enrolled. Subjects were randomized (3:2) to LPV/r 800/200 mg QD (n = 115) or 400/100 mg BID (n = 75). Subjects received TDF 300 mg and FTC 200 mg QD. Adherence to LPV/r through 96 weeks was measured using MEMS((R)) monitors. Median baseline VL and CD4(+) T cell count were 4.8 log(10) copies/ml and 216 cells/mm(3), respectively. Prior to week 96, 37% (QD) and 39% (BID) of subjects discontinued, primarily due either to adverse events (17% QD, 9% BID) or to loss to follow-up or nonadherence (12% QD, 17% BID). The proportion of subjects with VL <50 copies/ml [57% QD, 53% BID; p = 0.582 (ITT NC = F)], change in CD4 count (244 cells/mm(3) QD, 264 cells/mm(3) BID; p = 0.513), and evolution of resistance did not differ between groups through 96 weeks. Diarrhea (17% QD, 5% BID, p = 0.014) was the most common moderate or severe, study drug-related adverse event. Adherence to LPV/r was higher for the QD group than the BID group and declined over time in both groups. Time to loss of virologic response was significantly associated with adherence to LPV/r in both groups. LPV/r QD resulted in virologic response similar to LPV/r BID through 96 weeks in antiretroviral-naive subjects. Adherence was significantly higher in the QD group.
Molina
Jean-Michel
JM
Hôpital Saint Louis, AP-HP, and University of Paris 7, Paris, France.
Podsadecki
Thomas J
TJ
Johnson
Margaret A
MA
Wilkin
Aimee
A
Domingo
Pere
P
Myers
Robert
R
Hairrell
Jan M
JM
Rode
Richard A
RA
King
Martin S
MS
Hanna
George J
GJ
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; 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 / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir