KLEAN Study: Fosamprenavir/Ritonavir Associated With Similar Efficacy and Safety as Lopinavir/Ritonavir SGC in Treatment- Naive Patients Slideset on: Eron J Jr, Yeni P, Gathe J Jr, et al. The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial. Lancet. 2006;368:

clinicaloptions.com/hiv KLEAN Study: Fosamprenavir/Ritonavir Associated With Similar Efficacy and Safety as Lopinavir/Ritonavir SGC in Treatment-Naive Patients Eron J Jr, et al. Lancet. 2006;368: Background and Rationale  Lopinavir/ritonavir plus 2 NRTIs a widely used first-line regimen for treatment-naive individuals  Fosamprenavir/ritonavir has demonstrated promising efficacy and safety in treatment-naive individuals –No studies comparing fosamprenavir/ritonavir- and lopinavir/ritonavir-based regimens  Current study directly compared fosamprenavir/ritonavir vs lopinavir/ritonavir SGC, both in combination with abacavir/lamivudine, in treatment-naive individuals

clinicaloptions.com/hiv KLEAN Study: Fosamprenavir/Ritonavir Associated With Similar Efficacy and Safety as Lopinavir/Ritonavir SGC in Treatment-Naive Patients Eron J Jr, et al. Lancet. 2006;368: Schematic of Study Design Antiretroviral-naive patients with HIV-1 RNA > 1000 copies/mL; no CD4+ cell count restrictions (N = 878) Fosamprenavir/Ritonavir 700/100 mg twice daily + Abacavir/Lamivudine FDC 600/300 mg once daily (n = 434) Lopinavir/Ritonavir SGC 400/100 mg twice daily + Abacavir/Lamivudine FDC 600/300 mg once daily (n = 444) Week 48 FDC, fixed-dose coformulation. Stratification by baseline HIV-1 RNA (< vs ≥ 100,000 copies/mL)

clinicaloptions.com/hiv KLEAN Study: Fosamprenavir/Ritonavir Associated With Similar Efficacy and Safety as Lopinavir/Ritonavir SGC in Treatment-Naive Patients Eron J Jr, et al. Lancet. 2006;368:  Inclusion criteria –≥ 18 years of age –Treatment naive –HIV-1 RNA > 1000 copies/mL –Any CD4+ cell count allowed  Noninferiority defined as lower bound of 95% confidence interval for treatment difference > -12%  Primary endpoints –HIV-1 RNA < 400 copies/mL at Week 48 (intent-to-treat exposed [ITT-E], time to loss of virologic response [TLOVR] analysis) –Permanent treatment discontinuations due to adverse events Inclusion Criteria and Primary Endpoints

clinicaloptions.com/hiv KLEAN Study: Fosamprenavir/Ritonavir Associated With Similar Efficacy and Safety as Lopinavir/Ritonavir SGC in Treatment-Naive Patients Eron J Jr, et al. Lancet. 2006;368: Description of Current Analysis  Patients evaluated at baseline and Weeks 2, 4, 8, 12, 16, 24, 32, 40, and 48, or at withdrawal –HIV-1 RNA, CD4+/CD8+ cell count, clinical chemistries, hematologic profile, CDC classification, hepatitis B and/or C status (only at baseline) –Adverse events –Graded according to 1992 Division of AIDS toxicity grading scale –All abacavir hypersensitivity reactions reported as serious adverse events regardless of severity –Adherence  Genotyping performed on samples taken from patients experiencing virologic failure –Resistance mutations determined according to November 2005 International AIDS Society guidelines

clinicaloptions.com/hiv KLEAN Study: Fosamprenavir/Ritonavir Associated With Similar Efficacy and Safety as Lopinavir/Ritonavir SGC in Treatment-Naive Patients Eron J Jr, et al. Lancet. 2006;368:  Fosamprenavir/ritonavir noninferior to lopinavir/ritonavir soft-gel capsules (SGC) Main Findings Patient Outcomes at Week 48Fosamprenavir/Ritonavir (n = 434) Lopinavir/Ritonavir SGC (n = 444) HIV-1 RNA < 400 copies/mL, %  ITT-E, TLOVR7371 HIV-1 RNA < 50 copies/mL, %  ITT-E, TLOVR6665 Confirmed virologic failure, n (%)16 (4)24 (5) Median increase in CD4+ cell count, cells/mm 3 (IQR) 176 ( )191 ( ) Median change in lipid levels, mg/dL  Total cholesterol  LDL cholesterol  HDL cholesterol  Triglycerides HDL, high density lipoprotein; IQR, interquartile range; ITT, intent-to-treat exposed ; LDL, low density lipoprotein; TLOVR, Time to Loss of Virologic Response.

clinicaloptions.com/hiv KLEAN Study: Fosamprenavir/Ritonavir Associated With Similar Efficacy and Safety as Lopinavir/Ritonavir SGC in Treatment-Naive Patients Eron J Jr, et al. Lancet. 2006;368:  35 patients with virologic failure tested for resistance mutations –12 (34%) developed resistance mutations –None with major PI resistance mutations –5 with minor PI resistance mutations (I54I/L, K20K/R, and I62I/V) –7 with lamivudine resistance mutations –No significant differences in mutational patterns between arms  Both regimens similarly well tolerated, with few discontinuations due to adverse events –Suspected abacavir hypersensitivity reaction occurred in 6% of patients –Individuals coinfected with hepatitis B/C experienced higher incidence of grade 3/4 alanine aminotransferase elevations vs noncoinfected individuals (12% vs 1%) Patient Outcomes

clinicaloptions.com/hiv KLEAN Study: Fosamprenavir/Ritonavir Associated With Similar Efficacy and Safety as Lopinavir/Ritonavir SGC in Treatment-Naive Patients Eron J Jr, et al. Lancet. 2006;368:  Patients treated with fosamprenavir/ritonavir or lopinavir/ritonavir SGC, both in combination with abacavir/lamivudine, experienced comparable efficacy, safety, tolerability, and emergence of resistance mutations –Noninferiority of regimen established according to several sensitivity analyses –Similarity of responses observed in all subgroups assessed, including those with high viral loads (≥ 100,000 copies/mL) and low CD4+ cell counts (< 50 cells/mm3) –Confirmed virologic failure uncommon in both arms Key Conclusions