Abstract

WELBB05 - Oral Abstract Session

Elvitegravir once-daily is non inferior to raltegravir twice-daily in treatment experienced patients: 48 week results from a phase 3 multicenter, randomized, double blind study

Presented by Jean-Michel Molina (France).

J.-M. Molina¹, A. LaMarca², J. Andrade Villanueva³, B. Clotet⁴, N. Clumeck⁵, Y.-P. Liu⁶, L. Zhong⁶, A. Cheng⁶, J. Szwarcberg⁶, S.L. Chuck⁶, for the Study 145 Group

¹Hopital Saint Louis, Paris, France, ²Therafirst Medical Center, Fort Lauderdale, United States, ³Hospital Civil de Guadalajara, CUCS, U de G, Guadalajara, Mexico, ⁴Hospital Universitario Germans Trias i Pujol, Barcelona, Spain, ⁵C.H.U. St Pierre, Brussels, Belgium, ⁶Gilead Sciences, Foster City, United States

Background: Elvitegravir is an investigational once-daily integrase inhibitor with a long half life, and robust PK with trough levels of over 10-fold in excess of IC₉₅.
Methods: Adults with plasma HIV-1 RNA ≥1,000 copies/mL, and either resistance or six months experience to > 2 classes of antiretroviral drugs were randomized to receive blinded elvitegravir (EVG) 150 mg QD (85 mg if with atazanavir/lopinavir) or raltegravir (RAL) 400mg BID, in addition to a background regimen (BR) of a fully active ritonavir-boosted protease inhibitor and a second agent (investigator choice). The primary endpoint was the proportion of subjects achieving and maintaining HIV RNA < 50 copies/mL through Week 48 by TLOVR algorithm, with a non-inferiority threshold set at -10% (EVG-RAL).
Results: 702 patients were included in the ITT analysis, mean age was 45 years; 82% were male; 45% had CD4 cell counts ≤200; 26% had HIV RNA >100,000 copies/mL; and 63% had baseline resistance to two or more ARV classes (primary PI 33%, NRTI 72%, and NNRTI 61%). The most common BR combination was Darunavir , Ritonavir and Tenofovir DF (24%).

Key 48 Week Results	Elvitegravir	Raltegravir	Elvitegravir vs. Raltegravir
HIV RNA < 50 copies/mL(TLOVR) Responder, n (%)	207/351 (59%)	203/351 (58%)	95% CI, -6.0% to 8.2%, * p= 0.001 for non inferiority
Increase in CD4 cells/mm3, mean	138	147
Development of Integrase Resistance	16/62 (26%)	15/76 (20%)
Discontinuations due to Adverse Events, n (%)	9/354 (3%)	15/358 (4%)

[table 1]


Adverse events (AE) and laboratory abnormalities were similar.
Conclusion: This study demonstrated that once daily EVG was non-inferior to twice daily RAL in treatment-experienced HIV-1 infected subjects.