[37] EMTRICITABINE, DIDANOSINE AND EFAVIRENZ ONCE-DAILY (OD) VERSUS CONTINUED PI-BASED HAART (C) IN HIV-INFECTED ADULTS WITH UNDETECTABLE PLASMA HIV-RNA: 48-WEEK RESULTS OF A PROSPECTIVE RANDOMIZED MULTICENTER TRIAL (ALIZE-ANRS99)

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] EMTRICITABINE, DIDANOSINE AND EFAVIRENZ ONCE-DAILY (OD) VERSUS CONTINUED PI-BASED HAART (C) IN HIV-INFECTED ADULTS WITH UNDETECTABLE PLASMA HIV-RNA: 48-WEEK RESULTS OF A PROSPECTIVE RANDOMIZED MULTICENTER TRIAL (ALIZE-ANRS99)

[AUTHOR(S):] J. Molina¹, F. Ferchal¹, V. Journot², P Yéni³, W. Rozenbaum³, C. Rancinan², L. Morand-Joubert³, S. Fournier¹, P. Morlat², B. Dupont³, J. Delfraissy³, P. Dellamonica⁴, I. Poizot-Martin⁵, E. Rosenthal⁴, G. Chêne², and the Alize study group
¹Hôpital Saint-Louis, Paris, France, ²INSERM U593 Bordeaux, and ³AP-HP, Paris France, and hôpitaux de ⁴Nice et ⁵Marseille, France

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 37

[ABSTRACT:] Purpose of the study: To assess the efficacy and safety of a convenient once-daily antiretroviral regimen in patients with controlled viral replication under a PI-based regimen.

Methods: In a prospective, open-label, multicenter, non-inferiority study, NNRTI naïve patients receiving a PI-based regimen with plasma HIV-RNA level <400 copies/mL were randomized to continue their regimen (C) or to switch to OD. Virological failure was defined as a confirmed plasma HIV-RNA <400 copies/mL and success as a no virological failure from baseline to week 48. Non-inferiority was achieved if the upper limit of the 95% confidence interval (UCL) for the difference in proportion of success between arms was ≤15%. Intent-to-treat with missing = failure (ITT) and on-treatment on available data (OT) analyses were conducted.

Results: 355 patients were randomized. 86% were male, with a median age of 41 years, and 51% were homosexuals. 26% were CDC clinical stage C. 46% received NRTIs alone before HAART. Patients were mainly receiving indinavir (41%) or nelfinavir (36%) in combination with AZT/3TC or d4T/3TC at randomization and the median duration of PI therapy was 35 months. Median baseline CD4 count was 540 cells/mm³. The proportion of patients with virological success at 48 weeks in the ITT analysis was equivalent in the OD arm (89.3%) and the C arm (87.6%) with a treatment difference of –1.8% (UCL: 3.8%). In the OT analysis, the proportions were 96% and 93% in the OD and C arms respectively, with a treatment difference of –2.8% (UCL: 1.2%). The proportion of patients with plasma HIV RNA <50 copies/mL at week 48 was significantly high in the OD than in the C arm (95% versus 87%, p = 0.01). Median CD4 count increase was similar between arms (+13 and +21/mm³ in the C and OD arms respectively, p=0.7) Rates of treatment discontinuations were also similar between arms (12.4% and 10.1% in the C and OD arms respectively, p=0.5) as was the time to a serious (grade 4) adverse event (p=0.9). A significant increase in median fasting HDL cholesterol levels was ovserved in the OD arm as compared to the C arm (+0.2 versus +0.0 mmol/L respectively, p<10^-4).

Conclusions: The substitution of a PI-based regiment by a simple once-daily combination of emtricitabine, didanozine and efavirenz mainted full control of plasma HIV-RNA levels for 48 weeks and was well tolerated.

030714
37