JAC Advance Access originally published online on September 8, 2008
Journal of Antimicrobial Chemotherapy 2008 62(6):1374-1378; doi:10.1093/jac/dkn377
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Original research |
A randomized, controlled study evaluating an induction treatment strategy in which enfuvirtide was added to an oral, highly active antiretroviral therapy regimen in treatment-experienced patients: the INTENSE study
1 Hospital Universitari Germans Trias i Pujol and irsiCaixa Foundation, Ctra. de Canyet s/n, 08916 Barcelona, Spain 2 L. Sacco' Hospital, Via G. B. Grassi 74, Milan, Italy 3 Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga 15, Colonia Seccion XVI, Tlalpan, CP 14000, Mexico DF, Mexico 4 Clinical Institute of Medicine and Dermatology, Hospital Clinic, University of Barcelona, Villarroel, 170, 08036 Barcelona, Spain 5 Roche, Welwyn, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, UK 6 Roche, 340 Kingsland Avenue, Nutley, NJ 07110, USA 7 National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel
Received 27 May 2008; returned 28 June 2008; revised 31 July 2008; accepted 10 August 2008
* Corresponding author. Tel: +34-93-465-6374; Fax: +34-93-465-3968; E-mail: BClotet{at}irsicaixa.es
Objectives: The aim of the study was to compare the efficacy and safety of induction with the addition of enfuvirtide to a newly designed oral, highly active antiretroviral therapy (HAART) regimen versus HAART alone followed by a maintenance phase wherein participants were randomized to either continue/discontinue enfuvirtide while maintaining HAART or continue HAART alone (NCT00487188 [ClinicalTrials.gov] ).
Methods: Participants with HIV-1 RNA 
1000 copies/mL, CD4 count 200 cells/mm3 and genotype sensitivity score 2 (excluding enfuvirtide) were randomized 2:1 to enfuvirtide+HAART or HAART alone and assessed every 4 weeks. Participants achieving <50 copies/mL on two consecutive visits by week 24 entered a maintenance phase wherein those receiving enfuvirtide+HAART underwent another randomization 1:1 to maintain enfuvirtide+HAART or discontinue enfuvirtide; those receiving HAART alone continued their regimen. Virological and immunological endpoints were analysed at weeks 24 and 48.
Results: At 24 weeks, 20/31 (65%) participants in the enfuvirtide+HAART arm versus 8/16 (50%) participants in the HAART arm achieved <50 copies/mL. Median time to achieving <50 copies/mL was 57 versus 141 days in the enfuvirtide+HAART and HAART arms (P = 0.048). Withdrawals were similar between groups. In the maintenance phase, at 48 weeks, 14/19 (74%) in the original enfuvirtide+HAART arm (regardless of second randomization) versus 4/8 (50%) in the HAART arm had <50 copies/mL. During maintenance, there were two virological failures in the enfuvirtide+HAART continuation arm, one in the enfuvirtide discontinuation arm and none in the HAART arm.
Conclusions: Although limited by small participant numbers, these results suggest that treatment with enfuvirtide added to HAART may be an option for many patients.
Keywords: antiretroviral , HAART , HIV