Double Protease Inhibitor Therapy with Lopinavir/ritonavir (Kaletra) plus Atazanavir (Reyataz) in Treatment-naive Patients: LORAN Study

Double-protease inhibitor (PI) regimens are have been shown to be an effective therapeutic option for salvage therapy for treatment-experienced patients who have experienced prior treatment failures. However, double-PI therapy has not been extensively studied as an option for treatment-naive patients.

The LORAN study was a 72-week, randomized trial conducted in Germany. Treatment-naive patients were randomly assigned to receive lopinavir/ritonavir (Kaletra) in combination with either AZT/3TC (Combivir) or atazanavir (Reyataz).

The investigators analyzed virological failure in both groups, defined as viral load > 50 copies/mL at week 24. The primary study endpoints were metabolic side effects and quality of life; secondary endpoints were virological and immunological response. Twenty-four week results for 67 participants were presented at the 15th Conference on Retroviruses and Opportunistic Infections (CROI 2008) last week in Boston (February 3-6, 2008).

Results

• 24 of 30 patients (80%) in the lopinavir/ritonavir + Combivir arm achieved virological response (6 discontinued before week 24) compared with 15 of the 37 (41%) in the lopinavir/ritonavir + atazanavir arm (12 discontinued, 6 due to virological failure).

• Referring to "non-completion equals failure," the intent-to-treat analysis revealed significant differences in the rate of virological failure in the lopinavir/ritonavir + atazanavir arm compared to the lopinavir/ritonavir + Combivir arm (Chi-Q P = 0.015; Fisher's exact test P = 0.021).

• With regard to 47 on-study subjects at week 24, there were 10 failures in the lopinavir/ritonavir + atazanavir arm vs no failures in the lopinavir/ritonavir + Combivir arm (Chi-Q and Fisher's exact test P < 0.001).

• Virological failures in the lopinavir/ritonavir + atazanavir arm were low level (9 of 10 with HIV RNA < 700 copies/mL).

• Pharmacokinetic measurements showed reduced lopinavir concentrations in 1 of 7 tested subjects who experienced failure on the double-PI regimen.

Conclusion

According to the researchers, this is the first report of double-PI first-line therapy. Patients in the double-PI arm had a high rate of mostly low-level virological failure. They concluded that in this setting, "Atazanavir and lopinavir/ritonavir are less effective than the conventional reverse transcriptase inhibitor (RTI)-based regimens."

Further, they noted, "Significant treatment failure of an extended PI-based combination casts a new light on PI monotherapy in naive patients," as recently presented in the MONARK and M03-613-studies.

Finally, they concluded, "Further exploration of early RTI-sparing therapy with regard to metabolic side effects and quality of life is warranted."

2/15/08

Reference
K Ulbricht, M Stoll, G Behrens, and others. Double Protease Inhibitor, RTI-sparing Therapy Regimen in Naive HIV-1-infected patients: 24-Week Virologic Response Analysis of the LORAN Trial. 15th Conference on Retroviruses and Opportunistic Infections. Boston, MA. February 3-6, 2008. Abstract 780.

CROI 2008 Main Conference Page

  HOME PAGE OF SITE     • HOME PAGE OF SITE  • HIV and AIDS  • Hepatitis C  • Hepatitis B  • HIV-HCV Coinfection  • HIV-HBV Coinfection     • E-mail Update - Sign Up  • About Us - Contact Us