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.
BACKGROUND
Lopinavir-ritonavir is a preferred protease inhibitor co-formulation for initial HIV-1 treatment. Fosamprenavir-ritonavir has shown similar efficacy and safety to lopinavir-ritonavir when each is combined with two nucleoside reverse transcriptase inhibitors. We compared the two treatments directly in antiretroviral-naive patients.


METHODS
This open-label, non-inferiority study included 878 antiretroviral-naive, HIV-1-infected patients randomised to receive either fosamprenavir-ritonavir 700 mg/100 mg twice daily or lopinavir-ritonavir 400 mg/100 mg twice daily, each with the co-formulation of abacavir-lamivudine 600 mg/300 mg once daily. Primary endpoints were proportion of patients achieving HIV-1 RNA less than 400 copies per mL at week 48 and treatment discontinuations because of an adverse event. The intent-to-treat analysis included all patients exposed to at least one dose of randomised study medication. This study is registered with ClinicalTrials.gov, number NCT00085943.


RESULTS
At week 48, non-inferiority of fosamprenavir-ritonavir to lopinavir-ritonavir (95% CI around the treatment difference -4.84 to 7.05) was shown, with 315 of 434 (73%) patients in the fosamprenavir-ritonavir group and 317 of 444 (71%) in the lopinavir-ritonavir group achieving HIV-1 RNA less than 400 copies per mL. Treatment discontinuations due to an adverse event were few and occurred with similar frequency in the two treatment groups (fosamprenavir-ritonavir 53, 12%; lopinavir-ritonavir 43, 10%). Diarrhoea, nausea, and abacavir hypersensitivity were the most frequent drug-related grade 2-4 adverse events. Treatment-emergent drug resistance was rare; no patient had virus that developed reduced susceptibility to fosamprenavir-ritonavir or lopinavir-ritonavir.


CONCLUSIONS
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.
Eron
Joseph
J
Department of Medicine, Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA.
Yeni
Patrick
P
Gathe
Joseph
J
Estrada
Vicente
V
DeJesus
Edwin
E
Staszewski
Schlomo
S
Lackey
Philip
P
Katlama
Christine
C
Young
Benjamin
B
Yau
Linda
L
Sutherland-Phillips
Denise
D
Wannamaker
Paul
P
Vavro
Cindy
C
Patel
Lisa
L
Yeo
Jane
J
Shaefer
Mark
M
D002219:Carbamates / Q000008:administration & dosage / Q000627:therapeutic use*; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D061466:Lopinavir; D010755:Organophosphates / Q000008:administration & dosage / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000099227:Abacavir
D002219:Carbamates; D015224:Dideoxynucleosides; D005663:Furans; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D061466:Lopinavir; D010755:Organophosphates; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir; D013449:Sulfonamides; D000099227:Abacavir; C426859:fosamprenavir