Efficacy and Safety of Boosted Fosamprenavir (Lexiva) versus Lopinavir/ritonavir (Kaletra) in Treatment-naive HIV Patients with Hepatitis B or C Coinfection in the KLEAN Study

By Liz Highleyman

Lexiva

The KLEAN study was an open-label, randomized trial that demonstrated that ritonavir-boosted fosamprenavir (Lexiva) was non-inferior to lopinavir/ritonavir (Kaletra), each in combination with abacavir/3TC.

As reported at the recent 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Sydney, Australia (July 22-25, 2007), researchers evaluated the antiretroviral efficacy and safety of these regimens in a subset of KLEAN study participants coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV).

The total intention-to-treat (ITT) KLEAN study population included 878 subjects from the U.S., Europe, and Canada. Those with clinically relevant hepatitis or Grade 4 (severe) laboratory abnormalities at screening were excluded.

The primary endpoint was the Week 48 response rate (percentage with HIV RNA < 400 copies/mL using the TLOVR [Time to Loss of Virological Response] analysis).

Results:

• Out of the total 878 KLEAN participants in the ITT population:

- 26 patients (2.96%) were coinfected with HIV and HBV (14 in the fosamprenavir arm; 12 in the lopinavir/ritonavir arm);
- 85 patients (9.68%) were coinfected with HIV and HCV (47 and 38, respectively);
- 5 patients (0.56%) were triply infected with HIV, HBV, and HCV (3 and 2, respectively).

• For the overall ITT population, response rates for the primary endpoint were 73% in the fosamprenavir arm and 71% in the lopinavir/ritonavir arm.

• Among HIV positive subjects with neither HBV nor HCV coinfection, the respective response rates were 77% and 73%.

• Among the coinfected patients, the response rates in the fosamprenavir and lopinavir/ritonavir arms were:

- HIV-HBV coinfected: 79% and 58%, respectively;
- HIV-HCV coinfected: 43% and 61%, respectively;
- HIV-HBV-HCV triple infected: 0% (none of 3 subjects) and 50% (1 of 2 subjects), respectively.

• Grade 2-4 (moderate to severe) diarrhea, nausea, and drug-related hypersensitivity reactions occurred at similar rates in both treatment arms, and among patients with HIV monoinfection or HBV and/or HCV coinfection.

• Treatment-emergent grade 3-4 (serious to severe) liver enzyme elevations were observed at similar rates in the fosamprenavir and lopinavir/ritonavir arms, but occurred more often in patients with either HBV or HCV coinfection:

- HIV only: 1% (ALT and AST) fosamprenavir vs < 1% (ALT and AST) lopinavir/ritonavir;
- HIV-HBV coinfected: 21% (ALT and AST) vs 18% (ALT) and 27% (AST), respectively;
- HIV-HCV coinfected: 8% (ALT) and 10% (AST) vs 14% (ALT and AST) respectively;

• However, none of the 5 HIV-HBV-HCV triple infected patients experienced severe liver enzyme elevations in either treatment arm.

Conclusion

"Variable responses were observed in the few subjects coinfected with HBV or HCV in both treatment groups," the researchers concluded. "Transaminase elevations were more common in coinfected subjects compared to subjects without coinfection."

They added that, "Comparison of adverse events is difficult due to the limited number of coinfected subjects; however, no apparent differences in tolerability were noted between HBV [and] HCV negative and coinfected subjects."

St. Joseph's Comprehensive Research Institute, FL; GlaxoSmithKline, Research Triangle Park, NC; Presidio Ospedaliero di Busto Arsizio, Busto Arsizio, Italy; Chase Brexton Health Services, Baltimore, MD; Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Georgetown University Medical Center, Washington, DC; Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.

08/07/07

Reference
D Norris, L Patel, G Rizzardini, and others. Efficacy and safety of fosamprenavir/ritonavir (FPV/r) BID or lopinavir/ritonavir (LPV/r) BID in antiretroviral treatment-naive subjects co-infected with hepatitis B (HBV) or C (HCV) and HIV (The KLEAN Study). 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2007), July 22-25, 2007. Sydney, Australia. Abstract MOPEB059.