JAC Advance Access published online on July 18, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn278
Original research |
Initial therapy with nucleoside reverse transcriptase inhibitor-containing regimens is more effective than with regimens that spare them with no difference in short-term fat distribution: Hippocampe-ANRS 121 Trial
1 AP-HP, Groupe hospitalier Pitié-Salpétrière, Service de Maladies Infectieuses et Tropicales, Paris F-75013, France 2 UPMC Univ Paris 06, UMR S 720, Paris F-75013, France 3 INSERM, U720, Paris F-75013, France 4 AP-HP, Groupe hospitalier Pitié-Salpétrière, Laboratoire de Virologie, Paris F-75013, France 5 Université Pierre et Marie Curie-Paris6, EA 2387, Paris F-75013, France 6 AP-HP Groupe hospitalier Bichat-Claude Bernard, Laboratoire de toxicologie et pharmacologie clinique, Paris F-75018, France 7 AP-HP, Groupe hospitalier Saint Louis, Service de Maladies Infectieuses et Tropicales, Paris F-75010, France 8 Université Denis Diderot-Paris 7, Paris F-75010, France 9 AP-HP, Groupe hospitalier Avicenne, Service de Maladies Infectieuses et Tropicales, Bobigny F-93000, France 10 Université Paris 13, Bobigny F-93000, France
Received 29 February 2008; returned 23 April 2008; revised 31 May 2008; accepted 11 June 2008
* Correspondence address. INSERM U720, 56 Bd V Auriol, BP 335, 75625 Paris cedex 13, France. Tel: +33-1-42-16-42-82; Fax: +33-1-42-16-42-61; E-mail: dcostagliola{at}ccde.chups.jussieu.fr
Objectives: The aim of this study was to evaluate the impact on body fat of nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens compared with NRTI-containing therapy in HIV-1-infected antiretroviral (ARV)-naive patients.
Methods: A randomized, multicentre, open-label trial in ARV-naive patients. Subjects were randomized (2:1:1) to receive: (i) an NRTI-sparing regimen consisting of a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus a boosted protease inhibitor (PI/r); or (ii) an NRTI-containing regimen of (a) a PI/r plus two NRTIs or (b) an NNRTI plus two NRTIs. The primary endpoint was the change in subcutaneous limb fat measured by dual-energy X-ray absorptiometry at week (W) 96. Secondary endpoints included the proportion of patients with treatment failure, plasma HIV-RNA (pVL) <50 copies/mL and safety.
Results: One hundred and seventeen patients were enrolled between November 2003 and May 2004: 26% female; 42% from sub-Saharan Africa; median plasma HIV-RNA (pVL) 5.1 log10 copies/mL; median CD4 count 207 cells/mm3. A planned interim analysis demonstrated significantly lower treatment and virological responses with the NRTI-sparing strategy, resulting in premature study termination on 19 July 2005. The proportion of patients who remained on their assigned treatment strategy and had pVL <50 copies/mL on the NRTI-sparing regimen was 60.0%, compared with 82.5% on the NRTI-containing regimen at W24 (P = 0.009) and 66.7% and 82.5%, respectively, at W48 (P = 0.059). Treatment failure was associated with the NRTI-sparing strategy in patients with suboptimal adherence and with being from sub-Saharan Africa. No differences in fat distribution were noted.
Conclusions: An initial NRTI-sparing regimen is less successful and virologically less potent than standard NRTI-containing regimen and should not therefore be used as the first line of treatment.
Key Words: HIV-1 , NRTI-sparing regimen , antiretroviral efficacy , lipoatrophy syndrome , tolerance
Present address. AP-HP, Groupe hospitalier Necker-Enfant malades, Service de Maladies Infectieuses et Tropicales, Paris F-75006, France; Université Decartes-Paris 5, Paris F-75015, France; Centre Médical de l'Institut Pasteur; Centre d'Infectiologie Necker-Pasteur, Département Infection et Epidémiologie, Institut Pasteur, Paris F-75015, France.
Present address. AP-HP, Groupe hospitalier Bicêtre, Service de Médecine Interne et Maladies Infectieuses, le Kremlin-Bicetre F-94275, France; Université ParisSud 11, Le Kremlin-Bicêtre F-94275, France.