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.
OBJECTIVE
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 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.


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.
Duvivier
Claudine
C
AP-HP, Groupe hospitalier Pitié-Salpétrière, Service de Maladies Infectieuses et Tropicales, Paris F-75013, France.
Ghosn
Jade
J
Assoumou
Lambert
L
Soulié
Cathia
C
Peytavin
Gilles
G
Calvez
Vincent
V
Génin
Michèle Algarté
MA
Molina
Jean-Michel
JM
Bouchaud
Olivier
O
Katlama
Christine
C
Costagliola
Dominique
D
D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000000981:diagnostic imaging; D000328:Adult; D017954:Africa South of the Sahara; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors