Antiretroviral-Naïve Patients: 96-Week Results ... However, virologic response through 72 weeks was similar.3 Further, the Inhibitory. Quotient ..... M Thompson.
WePe12.3C12
Third IAS Conference on HIV Pathogenesis and Treatment 24–27 July 2005, Rio de Janeiro, Brazil
Once-Daily vs.Twice-Daily Lopinavir/ritonavir in Antiretroviral-Naïve Patients: 96-Week Results JM Molina1, A Wilkin2, P Domingo3, R Myers4, J Hairrell5, C Naylor5, T Podsadecki5, M King5, G Hanna5 1 Hôpital Saint Louis, Paris, France; 2Wake Forest University School of Medicine, Winston-Salem, NC; 3 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 4Phoenix Body Positive, Phoenix, AZ; 5Abbott Laboratories, Abbott Park, IL
B AC K G R O U N D
R E S U LT S
Lopinavir (LPV) is an HIV protease inhibitor (PI) that is co-formulated with ritonavir (r), which functions as a pharmacokinetic enhancer. LPV/r is marketed as Kaletra®. The approved adult dose of LPV/r is 400/100 mg twice daily (BID). In the U.S., adult dosage of LPV/r is also approved 800/200 mg once daily (QD) for antiretroviral (ARV)-naïve patients. Antiviral activity of LPV/r has been demonstrated in ARV-naïve and PI-experienced patients. In a phase 2 study of LPV/r in combination with stavudine (d4T) and lamivudine (3TC) in ARV-naïve patients (Study 720), 62% of patients maintained HIV RNA 1,000 copies/mL and any CD4 count.
Withdrew consent
5 (4%)
5 (7%)
• 190 patients were randomized 3:2 to LPV/r 800/200 mg QD (n=115) or 400/100 mg BID (n=75).
Nonadherence
5 (4%)
3 (4%)
• All patients also received TDF 300 mg and FTC 200 mg QD.
Other
3 (3%)
1 (1%)
Figure 1. Study 418 Schematic
Adverse Events/Laboratory Abnormalities LPV/r 800/200 mg QD + TDF 300 mg + FTC 200 mg QD (N=115)
• Moderate/severe, drug-related adverse events and grade 3/4 lab abnormalities occurring in >3% of patients in either treatment group are shown in Table 4.
Week 96
• At Week 96, a majority of subjects had total cholesterol 5 x ULN)
5%
3%
ns
1%
0
Triglycerides (>750 mg/dL)
6%
7%
ns
1%
2%
Amylase (>2 x ULN)
8%
7%
ns
0
0
Cholesterol (>300 mg/dL)
4%
6%
ns
1%
0
Table 5. Study 418: Summary of Lipid Values at Week 96
• Cumulative incidence of adverse events through 96 weeks was summarized.
Gender Male Female
Moderate or Severe LPV/r-Related Adverse Events or Grade 3/4 Lab Abnormality Diarrhea
LPV/r 800/200 mg QD (n=77)
LPV/r 400/100 mg BID (n=46)
Total cholesterol (mg/dL) 200 to 240 >240 to 300 >300 to 400 >400
50 (65%) 21 (27%) 5 (6%) 1 (1%) 0
22 (48%) 17 (37%) 7 (15%) 0 0
Triglycerides (mg/dL) 250 to 400 >400 to 750 >750 to 1200 >1200
59 (77%) 15 (19%) 2 (3%) 1 (1%) 0
39 (85%) 5 (11%) 1 (2%) 1 (2%) 0
Category
• Overall, for 98% of patients the maximum creatinine value was ≤1.5 mg/dL. One subject in each group demonstrated creatinine >3.0 mg/dL (acute renal failure – ARF). One case of ARF occurred at Week 34 in a 75-year-old male patient with a baseline creatinine clearance of 40 mL/min who was started on full dose TDF. Dosing guidelines implemented after the start of the study recommend that TDF be dosed every other day in this circumstance. Renal biopsy demonstrated non-specific changes with focal degenerative signs (cytoplasmic vacuolization) observed in some renal tubules. The second case of ARF occurred at Week 38 in a 54-year-old male patient, requiring temporary hemodialysis. Renal biopsy demonstrated tubulointerstitial nephritis. Both patients improved off study drug with creatinine levels returning to ≤1.7 mg/dL.
C O N C L U S I O N S • At Week 96, by intent-to-treat analysis with noncompleters considered failures, 57% of patients in the QD LPV/r+TDF+FTC regimen demonstrated HIV RNA 500 copies/mL occurring at any time during Weeks 12–96. No patient demonstrated lopinavir or tenofovir resistance, and only 4 patients demonstrated FTC resistance (Table 2).
R E F E R E N C E S
• CD4 cell count mean increases from baseline were comparable between treatment groups (Figure 4). Figure 2. Study 418: HIV RNA
