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
Duvivier, C.; Ghosn, J.; Assoumou, L.; Soulié, C.; Peytavin, G.; Calvez, V.; Génin, M.èl.A.é; Molina, J.-M.; Bouchaud, O.; Katlama, C.; Costagliola, D.; Beucler, I.; Dion, E.; Raffi, F.; Delfraissy, J.F.; Commoy, M.J.; Massip, P.; Garraffo, R.; Mazetier, L.; Izopet, J.; Chêne, G.; Racheline, A.; Jarousse, B.; Abgrall, S.; Obenga, G.; Phung, B.; Gerbe, J.; Bentata, M.; Honoré, P.; Rami, A.; Delcey, V.; Drener, M.; Parrinello, M.; Miailhes, P.; Lebouche, B.; Kouadjo, K.; Benmakhlouf, N.; Gou
Journal of Antimicrobial ChemoTherapy 62(4): 797-808
2008
ISSN/ISBN: 1460-2091 PMID: 18641035 DOI: 10.1093/jac/dkn278Document Number: 202886
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. 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. 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 log(10) copies/mL; median CD4 count 207 cells/mm(3). 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. 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.