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. [1] This study was published in the 5 August HIV/AIDS edition of the Lancet which has free online access. [2]

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

N 434 444
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

N 434 444
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.


  1. 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.
  2. The Lancet: HIV/AIDS special edition. 5 August 2006; 368: 476-482.

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