AEGiS-15IAC: TORO: 96 week virological and immunological response and safety evaluation of enfuvirtide with an optimized background regimen.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

TORO: 96 week virological and immunological response and safety evaluation of enfuvirtide with an optimized background regimen.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrB1058)

K Arastéh¹, A Lazzarin², B Clotet³, J Lalezari⁴, D Cooper⁵, K Henry⁶, M O'Hearn⁷, J Reynes⁸, P Piliero⁹, B Trottier¹⁰, J Montaner¹¹, S Walmsley¹², M Nelson¹³, C Katlama¹⁴, J Chung¹⁵, R DeMasi⁰, D Guimaraes¹⁵, L Huson⁰, L Donatacci¹⁵, C Wat⁰, T Kinchelow¹⁵, A Bertasso¹⁵, G D Miralles⁰, M Salgo¹⁵
¹EPIMED c/o Vivantes Auguste-Viktoria-Klinikum, II, Berlin, Germany; ²IRCCS, San Raffaele Vita-Salute University, Milan, Italy; ³Hospital Universitari Germans Trias i Pujol and the Institut de Recerca de la SIDA-Caixa Foundation, Badalona, Spain; ⁴Quest Clinical Research, San Francisco, United States; ⁵National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; ⁶Hennepin County Medical Center , Minneapolis, United States; ⁷Oregon Health & Science University, School of Medicine, Portland, United States; ⁸Hôpital Gui de Chauliac, Montpellier, France; ⁹Albany Medical College, Albany, United States; ¹⁰Clinique Médicale l'Actuel, Montréal, Canada; ¹¹University of British Columbia, Vancouver, Canada; ¹²Toronto General Hospital, Toronto, Canada; ¹³Chelsea and Westminster Hospital, London, United Kingdom; ¹⁴Service des Maladies Infectieuses et tropicales, Hopital Pitie-Salpetriere, Paris, France; ¹⁵Roche, Nutley, United States; ¹⁶Trimeris, Durham, United States

BACKGROUND: The TORO studies up to week 48 have demonstrated the safety and efficacy of enfuvirtide (ENF) plus an optimized background (OB) compared to OB alone in heavily treatment-experienced patients. Patients on OB either meeting protocol defined criteria for virological failure or at week 48 were permitted to revise their OB and add ENF.

METHODS: Since only 4 patients in the OB arm remained on originally randomized treatment after week 48, the 96 week analysis only describes virological, immunological response and safety in those originally randomized to ENF+OB (N=661). For HIV RNA analyses (<400 copies/mL) the ITT population considered discontinuations as failure (D/C=F) and for the percentage of patients achieving CD4 improvement of at least 50, 100 or 200 c/muL from BL the ITT population considered D/C or missing (M)=F. The responses for those staying on treatment (OT) are also presented based on observed data.

RESULTS: For patients on ENF+OB; 583, 506, 441 and 368 patients remained OT at 24, 48, 72 and 96 weeks, respectively.

Response parameter	Data handling rule	Week 24	Week 48	Week 72	Week 96
HIV RNA <400 copies/mL	ITT: D/C=F	37.4%	34.0%	29.2%	26.5%
HIV RNA <400 copies/mL	OT	42.4%	44.5%	43.8%	47.6%
CD4 increase ≥50	ITT: D/C or M=F	48.6%	50.5%	44.9%	37.8%
CD4 increase ≥100	ITT: D/C or M=F	29.8%	38.0%	38.0%	31.5%
CD4 increase ≥200	ITT: D/C or M=F	7.4%	14.5%	18.2%	18.5%
CD4 increase ≥50	OT	61.3%	69.9%	72.1%	75.8%
CD4 increase ≥100	OT	37.6%	52.5%	60.9%	63.0%
CD4 increase ≥200	OT	9.4%	20.1%	29.1%	37.0%

134 (20.2%) patients discontinued for safety reasons; 47 (7.1%) due to an ISR, 81 (12.2%) due to AEs or lab abnormality and 6 (<1.0%) due to death. Additional long-term safety data will be presented.

CONCLUSIONS: A majority of patients on the ENF+OB arm completed 96 weeks (55.7%). A significant number of patients 26.5% (ITT) [47.6% (OT)] demonstrated<400 copies/mL at 96 weeks and no new safety issues were identified.

Keywords: AEGIS, HIV Envelope Protein gp41, Peptide Fragments, pentafuside, Humans, virology, immunology, methods

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MoOrB1058