The KLEAN Study: 48-week Analysis Demonstrates Non-inferiority and Rare Resistance

KLEAN was an international, randomized study of 878 treatment-naive HIV positive subjects comparing the safety and efficacy of twice-daily ritonavir-boosted fosamprenavir (Lexiva) to twice-daily lopinavir/ritonavir (Kaletra). All participants also took the fixed-dose coformulation of abacavir/3TC (Epzicom) once daily. Results were presented at the recent International AIDS Conference in Toronto and published in the August 5, 2006 issue of The Lancet.

At the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), taking place this week in San Francisco, researchers presented results from an analysis of virological response and resistance patterns of subjects in KLEAN who experienced virological failure over the course of 48 weeks.

Patients with confirmed virological failure -- defined as either a failure to achieve plasma HIV RNA below 400 copies/mL by Week 24, or confirmed viral load rebound to 400 copies/mL or greater - had drug resistance evaluated using the PhenoSense GT assay (Monogram BioSciences) at baseline and at the time of virological failure.

Results

At 48 weeks, 73% of subjects in the fosamprenavir/ritonavir arm had HIV RNA below 400 copies/mL, compared to 71% in the lopinavir/ritonavir arm, thereby establishing the non-inferiority of boosted fosamprenavir.

A total of 40 subjects (5%) met the criteria for virological failure: 16 in the fosamprenavir/ritonavir arm and 24 in the lopinavir/ritonavir arm.

Of these, 10 did not achieve viral loads below 400 copies/mL by Week 24, while 30 experienced viral rebound over 48 weeks.

Virus from 26 of 37 subjects with available on-treatment genotypic test results had no treatment-emergent resistance mutations at the time of confirmed virological failure.

Among the remaining subjects, the most common treatment-emergent resistance patterns observed were resistance to NRTIs (n = 7), then PIs (n = 4), then NNRTIs (n = 2).

No differences were seen between the 2 treatment arms with respect to emergence of on-treatment genotypic resistance.

No reduced susceptibility to fosamprenavir/ritonavir or lopinavir/ritonavir was observed in the 37 subjects with on-treatment phenotypic data.

Conclusion

The researchers concluded, "In treatment-naive subjects fosamprenavir/ritonavir [twice daily] was non-inferior to lopinavir/ritonavir [twice daily], each given with abacavir/3TC fixed-dose combination [once daily]. Virologic failure was rare and similarly distributed across treatment arms. Antiviral drug resistance was rare and no reduced susceptibility to PIs was detected."

Bichat Medical School/University of Paris; Univ. of North Carolina, Chapel Hill; Hospital Universitari Germans Trias I Pujol, Barcelona, Spain; AIDS Research Consortium of Atlanta; Rose Medical Center, Denver, CO; GlaxoSmithKline, Research Triangle Park, NC.

09/29/06

Reference
P Yeni, J Eron, B Clotet, and others. The KLEAN Study: FPV/r BID vs LPV/r BID + (ABC/3TC) QD in ART naive subjects. 48 week Analysis demonstrates rare resistance and non-inferiority. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, CA. September 27-30, 2006. Abstract 1056.

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