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Substitution of raltegravir for ritonavir-boosted
protease inhibitors in HIV-infected patients:
the SPIRAL study
Esteban Martinez
a,M
, Marı ´a Larrousse
a,M
, Josep M. Llibre
b
,
Felix Gutierrez
c
, Maria Saumoy
d
, Antonio Antela
e
, Hernando Knobel
f
,
Javier Murillas
g
, Juan Berenguer
h
, Judit Pich
a
, Ignacio Pe ´rez
a
,
Jose ´ M. Gatell
a
, for the SPIRAL Study Group
Background: Switching to raltegravir in selected patients treated with ritonavir-boosted
protease inhibitors may result in similar efficacy and lower plasma lipids.
Methods: SPIRAL is a 48-week multicentre, open-label trial in which HIV-infected
adults with less than 50 copies/ml of plasma HIV RNA for at least the previous 6 months
on ritonavir-boosted protease inhibitor-based therapy were randomized (1 : 1) to switch
from the ritonavir-boosted protease inhibitor to raltegravir or to continue on ritonavir-
boosted protease inhibitor-based therapy. Primary endpoint was the proportion of
patients free of treatment failure (noncompleter ¼ failure) at 48 weeks. SPIRAL study
was powered to show noninferior efficacy of raltegravir-based therapy with a margin of
12.5%.
Results: Two hundred and seventy-three patients assigned to switch to raltegravir
(n ¼ 139) or to continue ritonavir-boosted protease inhibitor (n ¼ 134) were included
in the efficacy analysis. At 48 weeks, 89.2% (raltegravir-based therapy) and 86.6%
(ritonavir-boosted protease inhibitor-based therapy) of the patients remained free of
treatment failure [difference 2.6%; 95% confidence interval (CI) 5.2 to 10.6]. A total of
96.9% (raltegravir-based therapy) and 95.1% (ritonavir-boosted protease inhibitor-
based therapy) of the patients remained free of virological failure (difference 1.8%;
95% CI 3.5 to 7.5). Switching to raltegravir was associated with significant decreases
in plasma lipids and total-to-HDL cholesterol ratio relative to continuing ritonavir-
boosted protease inhibitor. Severe adverse events and study drug discontinuations due
to any adverse event occurred in 4 and 2% of the patients in each group.
Conclusion: In patients with sustained virological suppression on ritonavir-boosted
protease inhibitor-based therapy, switching from ritonavir-boosted protease inhibitor to
raltegravir demonstrated noninferior efficacy and resulted in a better lipid profile at 48
weeks than continuing ritonavir-boosted protease inhibitor.
ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
AIDS 2010, 24:1697–1707
Keywords: clinical trial, raltegravir, ritonavir-boosted protease inhibitors,
simplification
a
Hospital Clı ´nic-IDIBAPS, University of Barcelona, Barcelona,
b
Hospital Germans Trı ´as i Pujol and IrsiCaixa Foundation,
Badalona,
c
Hospital General Universitario de Elche, Elche,
d
Hospital de Bellvitge, L’Hospitalet de Llobregat, Barcelona,
e
Hospital
de Santiago, Santiago de Compostela,
f
Hospital del Mar, Barcelona,
g
Hospital Son Dureta, Palma de Mallorca, and
h
Hospital
Gregorio Maran ˜o ´ n, Madrid, Spain.
Correspondence to Esteban Martı ´nez, MD, PhD, Infectious Diseases Unit, Hospital Clı ´nic-Institut d’Investigaciones Biome `diques
August Pi i Sunyer (IDIBAPS), University of Barcelona, C/Villarroel 170, 08036 Barcelona, Spain.
Tel: +34 93 2275430; fax: +34 93 4514438; e-mail: esteban@fundsoriano.es
M.L. and E.M. contributed equally to the writing of the article.
Received: 18 February 2010; revised: 25 March 2010; accepted: 28 March 2010.
DOI:10.1097/QAD.0b013e32833a608a
ISSN 0269-9370 Q 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
1697