Oral Presentation: PS1 - Initiation of Antiretroviral Therapy PS1/3 - Lower rate of virological suppression in naive patients initiating HAART with NRTI-sparing regimen compared to standard NRTI-containing regimen: Results from Hippocampe – ANRS 121 Trial.

Duvivier C.1, Ghosn J.1, Assoumou L.2, Soulie C.3, Peytavin G.4, Calvez V.3, Molina J.M.5, Jarousse B.6, Allavena C.7, Delfraissy J.F.8, Katlama C.1, Costagliola D.2

1Department of Infectious Diseases, La Pitié Salpêtrière Hospital, Université Pierre et Marie Curie; Inserm U720, Université Pierre et Marie Curie, Paris, France, 2Inserm U720, Université Pierre et Marie Curie, Paris, France, 3Virology Department, Pitié Salpêtrière Hospital, Université Pierre et Marie Curie, Paris, France, 4Clinical Pharmacology Department, Bichat-Claude Bernard Hospital, Paris, France, 5Department of Infectious Diseases, Saint Louis Hospital, Paris, France, 6Department of Internal Medecine, Avicenne Hospital, Bobigny, France, 7Department of Internal Medecine , L’Hôtel Dieu Hospital, Nantes, France, 8Department of Internal Medecine, Le Kremlin-Bicêtre Hospital, Le Kremlin Bicêtre, France

Objectives: To evaluate a strategy of NNRTI/boosted-PI, compared to standard triple combination, on the occurrence of lipoatrophy and virological efficacy in naive HIV-1 infected patients. Methods: ARV-naive patients were randomised (2:1:1) to either PI+NNRTI (Gp1) or standard therapy, 2NRTI+ either PI (Gp2) or NNRTI (Gp3) if they had plasma HIV RNA (pVL) >5000 copies/mL and CD4 count <350/mm3. The study-treatments were lopinavir/r 100/400mg bid (133/533 mg bid in Gp 1) or indinavir/r 100/400mg bid (100/600 mg bid in Gp 1); efavirenz or nevirapine and all NRTIs except D4T and DDC. The primary endpoint was the evolution of limbs subcutaneous fat between baseline and W96. Virological analysis was planned to evaluate the proportion of patients with pVL <50 copies/mL comparing the NNRTI+PI group to both standard groups mixed together. Intent-to-treat (ITT) (missing values or change of treatment strategy=failure) and on-treatment (OT) analyses were performed. Results: Overall, 117 patients were randomised. Baseline median pVL was 4.99 log10 copies/mL IQR:[4.55-5.42] and median CD4 cell count 203/mm3 [138-281], with no imbalance between groups. In Gp1, 63% patients received efavirenz and 37% nevirapine; 21.5% received indinavir/r and 78.5% lopinavir/r. Up to week 36, study-treatment discontinuation occurred in 30% (n=18/60), 28% (n=8/29) and 14% (n=4/28) of patients in Gp1, Gp2 and Gp3, respectively. By ITT-analysis, the proportion of patients with pVL <50 copies/mL was 57.9% at W12 in Gp2+3 versus 36.7% in Gp1 ([95% CI:3.1-37.5], p=0.02); 80.7% in Gp2+3 versus 60% in Gp1 ([95% CI: 4.1-35.7], p=0.01) at W24 and 78.9% in Gp2+3 versus 61.7% in Gp1 ([95% CI:0.6-32.5], p=0.04) at W36. Similar results were obtained in OT-analysis. Following these results, the trial was discontinued on July 19th, 2005. Conclusion: In ARV-naive patients, a NNRTI/PI strategy was virologically less potent than standard NRTI-containing-HAART. Therefore, such strategy should not be recommended for first-line antiretroviral therapy. Contact: Dr. Claudine Duvivier, Department of Infectious Diseases, La Pitié Salpêtrière Hospital, Université Pierre et Marie Curie; Inserm U720, Université Pierre et Marie Curie, 47-83 boulevard de l'hôpital, 75651 Paris, France, Email: claudine.duvivier@psl.ap-hop-paris.fr