Data from the KLEAN (Kaletra vs. Lexiva with Epivir and Abacavir in ART-Naive Patients) study were presented last week at the XVI International AIDS Conference in Toronto. Further details were provided in an article in the August 5, 2006 special issue of The Lancet coinciding with the conference.

According to the U.S. federal HIV treatment guidelines, lopinavir/ritonavir (Kaletra) is a preferred protease inhibitor (PI) for initial treatment of HIV infection. Ritonavir-boosted fosamprenavir (Lexiva) has shown similar efficacy and safety to lopinavir/ritonavir when each is combined with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).

In the current study, researchers compared the two treatments head-to-head in combination with the abacavir (Ziagen)/3TC (lamivudine, Epivir) co-formulation known as Epzicom in patients being treated for the first time.

This international, open-label, Phase IIIb non-inferiority study included 878 antiretroviral-naive, HIV-infected patients randomly assigned to receive either fosamprenavir/ritonavir 700 mg/100 mg twice daily or lopinavir/ritonavir 400 mg/100 mg twice daily, each with abacavir/3TC 600 mg/300 mg once daily. At study entry, participants had viral loads of at least 1000 copies/mL; there were no exclusion criteria based on CD4 cell count.

Primary endpoints were proportion of patients achieving HIV RNA less than 400 copies/mL at week 48 using a metric known as TLOVR (Time to Loss of Virologic Response) and treatment discontinuations due to adverse events. The intent-to-treat analysis included all patients exposed to at least one dose of randomized study medication.

Results

676 patients (77%) completed the study.

At week 48, fosamprenavir/ritonavir was shown to be non-inferior to lopinavir/ritonavir (95% CI -4.84-7.05).

After 48 weeks, 315 of 434 patients (73%) in the fosamprenavir/ritonavir group achieved HIV RNA less than 400 copies/mL, compared with 317 of 444 patients (71%) in the lopinavir/ritonavir arm.

285 patients (66%) in the fosamprenavir/ritonavir arm and 288 (65%) in the lopinavir/ritonavir arm achieved HIV RNA less than 50 copies/mL.

The median CD4 cell increase was 176 cells/mm3 in patients who received fosamprenavir/ritonavir and 191 cells/mm3 in patients who received lopinavir/ritonavir.

Treatment discontinuations due to an adverse event were few, and occurred with similar frequency in both arms (fosamprenavir/ritonavir 12% vs lopinavir/ritonavir 10%).

The most frequently reported drug-related grade 2-4 adverse events were diarrhea (11%-13%), nausea (5%-6%), and abacavir hypersensitivity reactions (4%-6%), with similar rates in both arms.

Similar increases in fasting lipid values were observed in both arms.

Treatment-emergent drug resistance was rare; no patient had virus that developed reduced susceptibility to fosamprenavir/ritonavir or lopinavir/ritonavir.

Conclusion

In conclusion, the researchers wrote, "Fosamprenavir/ritonavir twice daily in treatment-naive patients provides similar antiviral efficacy, safety, tolerability, and emergence of resistance as lopinavir/ritonavir, each in combination with abacavir/lamivudine."

"Protease inhibitors continue to be a key component of antiretroviral therapy and this new information reinforces the efficacy and safety of Lexiva/ritonavir for treatment-naive patients with HIV," said lead study author Joseph Eron, MD.

8/22/06

Sources

J Eron JR. P Yeni, J Gathe Jr, and others. 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. The Lancet 368(9534): 476-482. August 5, 2006.

GlaxoSmithKline and Vertex Pharmaceuticals. Head-to-Head Study Comparing LEXIVA (fosamprenavir calcium) to Kaletra Presented at IAC 2006 and Published in The Lancet. Press release. August 17, 2006.