Fosamprenavir/r is non-inferior to Kaletra in treatment naive patients
Simon Collins, HIV i-Base
Joseph Eron from the University of North Carolina presented 48-week data from a large international randomised open-label study comparing fosamprenavir and lopinavir/r in 878 treatment naive patients, which showed no significant differences between the two treatments in any analysis.  This study was published in the 5 August HIV/AIDS edition of the Lancet which has free online access. 
Both groups used twice-daily PI regimens and all patients also received fixed dose abacavir/3TC once-daily, with switching allowed for suspected abacavir hypersensitivity (HSR).
Median baseline CD4 and viral load counts were just under 200 cells/mm3 (with 15-18% < 50 cells/mm3) and 5.1 log copies/mL (with half over 100,000 copies/mL) and are detailed in Table 1. Median age was 37 years; 78% were male; 58% were Caucasian; and 11% were CDC Class C.
Table 1: Baseline characteristics in KLEAN study
|Gender M/F %||78/22||78/22|
|Viral load log copies/mL (IQR)||5.1 (4.6-5.5)||5.1 (4.6-5.5)|
|Viral load >100,00 copies/mL (%)||55%||53%|
|CD4 cells/mm3 (IQR)||188 (88-280)||194 (79-297)|
|CD4 <50 cells/mm3 (%)||15%||18%|
Primary endpoints were proportion of subjects with viral load <400 copies/mL at week 48, [time to loss of virologic response (TLOVR)] and treatment discontinuations due to adverse events (AEs). Protocol-defined virologic failure (VF) was failure to achieve viral load <400 copies/mL by week 24 or confirmed viral rebound >400 copies/mL.
The two groups had similar results from primary (% <400 c/mL, and discontinuations) and secondary endpoints (%<50 copies/mL, TLOVR, change in CD4), and are detailed in Table 2.
Approximately 71% and 65% in each group maintained viral suppression <400 and <50 copies/mL respectively after one year. Results of the two groups were similar when stratified by baseline viral load >5log or CD4 <50 cell/s/mm3,
77% patients (679/878) completed the study: around 100 patients withdrew from each arm before week 48. Discontinuations were similar: adverse events (27/25), lost to follow up (23/32), patients decision (16/9), non-adherence (13/10), virological failure (9/6), other (12/17) in the fosamprenavir/lopinavir groups respectively.
Table 2: Fosamprenavir/r vs lopinavir/r in treatment-naive patients: 48-week results
|VL <400 copies/mL (%) *||73%||71%|
|VL <50 copies/mL (%))||66%||65%|
|Median CD4 change cells/mm3 (IQR)||+176 (106-281)||+191 (124-287)|
|Virological failure; n (%)||16 (4%)||24 (5%)|
|Drug related Grade 2-4 AEs; n (%)||55 (13%)||46 (10%)|
|Discontinuation due to AEs; n (%)||53 (12%)||43 (10%)|
(*95% CI -3.36, 5.47)
The incidence of ABC HSR was 6 and 4% and rash was slightly higher in patients using fosamprenavir (3% vs <1%). Similar increases in median fasting lipid values (total cholesterol, LDL, HDL and triglycerides) were observed for both regimens.
Drug resistance in the 5% patients (n=40) with virological failure (>400 copies/mL) was very low. In 35 patients with baseline and week 48 genotype results only 4 showed minor PI-associated mutations (I54I/L, K20K/R, I62I/V) and 7 showed RTI-associated mutations.
This study also reported very high adherence rates (calculated by percentage of returned pills) of >/= 98% for the protease inhibitors and 99.4% for abacavir/3TC.
This was a non-inferiority study with 12% margin, but in these treatment-naive patients, dosed twice daily, the results were similar or the same in the two groups, in all analyses of primary and secondary endpoints: CD4 and viral load responses of the total population, and sub analyses for patients with baseline viral load </> 100,000, and baseline CD4 <50, 50-200, and >200 cells/mm3; ITT (E): TLOVR; discontinuations, side effects and laboratory abnormalities (including lipid changes).
Of note, this study reported very high adherence and this may be one of the few differences that could appear in the clinic rather than trial setting. The pill count for fosamprenavir/ is 2 pills, twice-daily plus 100mg ritonavir, twice-daily, compared to 2 tablets twice daily for the new formulation of lopinavir/r.
During the conference, GSK announced that it would reduce the net price of fosampranavir would be reduced by 30% to UK clinics.
- Eron J, Yeni P, Gathe, J et al. The KLEAN Study: fosamprenavir + ritonavir (FPV/r) versus lopinavir/ritonavir (LPV/r) in antiretroviral-naive (ARTnaive) HIV-1 infected adults over 48 weeks. XVI International AIDS Conference, Toronto, Canada. 13-18 August 2006. Late breaker abstract THLB0205.
- The Lancet: HIV/AIDS special edition. 5 August 2006; 368: 476-482.