1484 • CID 2007:44 (1 June) • HIV/AIDS
H I V / A I D SM A J O R A R T I C L E
Efficacy and Safety of Atazanavir-Based Highly Active
Antiretroviral Therapy in Patients with Virologic
Suppression Switched from a Stable, Boosted or
Unboosted Protease Inhibitor Treatment Regimen:
The SWAN Study (AI424-097) 48-Week Results
Jose Gatell,1Dominique Salmon-Ceron,2Adriano Lazzarin,3Eric Van Wijngaerden,4Francisco Antunes,6
Clifford Leen,7Andrzej Horban,8Victoria Wirtz,9Linda Odeshoo,9Monique Van den Dungen,5Claudia Gruber,5
and Emilio Ledesma,9,afor the SWAN Study Groupb
1Hospital Clinic–IDIBAPS, University of Barcelona, Barcelona, Spain;
Ziekenhuizen, Leuven, and5Pharmaceutical Research Institute, Braine l’Alleud, Belgium;6Instituto Bento da Rocha Cabral, Lisbon, Portugal;7University
of Edinburgh, Scotland;8Wojewodzki Hospital, Warsaw, Poland; and
2Hospitalier Cochin, Paris, France;3San Raffaele Turro, Milan, Italy;4Universitaire
9Bristol-Myers Squibb, Pharmaceutical Research Institute, Wallingford, Connecticut
virus (HIV) infection that has previously been studied in cohorts of treatment-naive and treatment-experienced
patients. Limited data are available on the usefulness of switching from a PI-based regimen to a regimen based
on a different PI, such as atazanavir, in HIV-infected patients experiencing virologic suppression but seeking
The Switch to Another Protease Inhibitor (SWAN) study was a 48-week, open-label trial involving
HIV-positive patients with virologic suppression who were receiving stable PI-based regimens (with or without
ritonavir). Patients were randomized 2:1 to switch to atazanavir (400 mg per day)—or, if they were receiving
tenofovir, to atazanavir-ritonavir (300/100 mg per day)—or to continue to receive their existing PI. The proportion
of patients who experienced virologic rebound (defined as an HIV RNA load ?50 copies/mL) was compared
through study week 48.
Patients either received an atazanavir-containing regimen (278 patients) or continued to receive a
comparator PI-containing regimen (141 patients). The proportion of patients who experienced virologic rebound
was significantly lower among those who switched to an atazanavir-containing regimen (19 [7%] of 278) than it
was among those who continued to receive a comparator PI regimen (22 [16%] of 141;
switched to atazanavir therapy experienced significantly fewer total cholesterol, fasting triglyceride, and non–high
density lipoprotein cholesterol elevations than did patients in the comparator PI group (
atazanavir had comparable rates of adverse event–related discontinuation and serious adverse events.
In patients with virologic suppression who were receiving other PIs, switching to a once-per-day
regimen containing atazanavir provided better maintenance of virologic suppression (as demonstrated by signif-
icantly lower rates of virologic rebound and treatment failure than those observed with continued unmodified
therapy), a comparable safety profile, and improved lipid parameters, compared with those for patients who
continued their prior PI-based regimen through 48 weeks.
Atazanavir is a once-daily protease inhibitor (PI) for the treatment of human immunodeficiency
). Patients whoP p .004
); patientsreceivingP ! .001
HAART has significantly decreasedmorbidityandmor-
tality among and has extended the life expectancy of
Received 19 September 2006; accepted 12 February 2007; electronically
published 25 April 2007.
Reprints or correspondence: Dr. Jose Gatell, Infectious Diseases Unit, Hospital
Clinic–IDIBAPS, University of Barcelona, Villarroel, 170.08036, Barcelona, Spain
Clinical Infectious Diseases 2007;44:1484–92
? 2007 by the Infectious Diseases Society of America. All rights reserved.
individuals with HIV infection . Adherence to
HAART regimens is essential for successful virologic
and treatment outcomes . The incidence of treat-
ment-limiting adverse events, the frequent dosing
schedule, and the effect of a high daily pill burden(with
associated food requirements) render many individuals
aPresent affiliation: Sanofi Pasteur, Lyon, France.
bMembers of the study group are listed at the end of the text.
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HIV/AIDS • CID 2007:44 (1 June) • 1485
ritonavir (RTV) administered at a dosage of ?200 mg per day with a nucleoside backbone. Data are expressed as no. (%) of patients. ATV, atazanavir;
NRTI, nucleoside reverse-transcriptase inhibitor.
Study design and patient disposition. The current antiretroviral regimen was defined as a comparator protease inhibitor (PI) with or without
unable to maintain adherence to HAART for extended periods
of time [3, 4].
Protease inhibitors (PIs) are commonly used as a critical
component of HAART, but the pharmacologic and pharma-
cokinetic characteristics (including limited oral bioavailability
and complex dosing schedules) of many drugs in this class may
create challenges for patient compliance [5, 6].
Atazanavir is a potent PI with a pharmacokinetic profile that
allows once-daily oral administration with or without ritonavir
boosting. Atazanavir, administered at a dosage of 400 mg per
day, showed efficacy similar to that of efavirenz and nelfinavir
in treatment-naive patients [7, 8]. Atazanavir-ritonavir, ad-
ministered at 300/100 mg per day, has demonstratedlong-term
efficacy comparable to that of lopinavir-ritonavir in patients
who have experienced multiple virologic failures .
The SWAN study explores whether patients who were re-
ceiving stable suppressive therapy (their first or secondHAART
regimen and no prior history of PI failure) that included a
boosted or unboosted PI would maintain virologic suppression
through 48 weeks after switching to an atazanavir-containing
regimen. Switching from a more complex PI-based regimen to
a simpler, atazanavir-based regimen may be associated with
better gastrointestinal tolerability, improved plasma lipid pa-
rameters, and potential clinical benefits for patients.
HIV-positive patients with virologic suppression who were re-
This was a 48-week, open-label trial enrolling
ceiving stable PI-based regimens with or without ritonavir(fig-
ure 1). The study was approved by the internal review boards
at each site, and all patients gave written informed consent.
Patients were randomized 2:1 either to receive an atazanavir-
containing regimen or to continue their current PI-containing
regimen. Patients in the switch group weretoreceiveunboosted
atazanavir (400 mg once per day) instead of their current PI.
When tenofovir disoproxil fumarate was used as a part of the
nucleoside backbone at study entry, patients were switched to
atazanavir-ritonavir (300/100 mg per day), but the other com-
ponents of the HAART regimen remained unchanged. Ran-
domization of patients who were receiving a ritonavir-boosted
PI at study entry was limited to 50% of the sample size.
Prospective patients were required to be
receiving a stable PI-containing regimen (their first or second
HAART regimen) with or without ritonavir. Patients with a
history of virologic failure while receiving PI-based HAART
were excluded from the study. Patients who had experienced
transcriptase inhibitor regimen were eligible for inclusion in
the study. Patients were required to have a suppressed plasma
viral load (defined as an HIV RNA load of !50 copies/mL) for
?3 months prior to screening and a CD4+cell count 150 cells/
mm3. The current PI component(s) of the patients’ therapy
had to be dosed at least twice daily and/or include 13 pills per
Efficacy end points.
A total of 372 randomized patients
provided 90% power to demonstrate the noninferiority of the
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1492 • CID 2007:44 (1 June) • HIV/AIDS
imen and the comparator PI regimen exhibited comparable
in the atazanavir arm of the study and were confirmed through
48 weeks. However, the clinical significance of these changes
in lipid parameters has not been determined.
MEMBERS OF THE SWAN STUDY GROUP
Joaquin Portilla Sogorb (Hospital General Universitario de Al-
icante, Alicante, Spain), Felix Gutierrez, (Hospital General
Universitario De Elche, Alicante, Spain), Federico Pulido(Hos-
pital Universitario 12 De Octubre, Madrid, Spain), Juan Ber-
enguer (Hospital Gral, Universitario Gregorio Maran ˜on, Ma-
drid, Spain), Alberto Arranz (Hospital Universitario Principe
De Asturias, Madrid, Spain), Vicente Estrada (Hospital Clinico
San Carlos, Madrid, Spain), Esteban Ribera Pascuet (Hospital
Universitari Vall D’Hebron, Barcelona, Spain), Jean-Pierre Bru
(Centre Hospitalier General Service des Maladies Infectieuses,
Annecy, France), Willy Rozenbaum (Hopital Tenon Service des
Maladies Infectieuses, Paris Cedex, France),PierreDellamonica
(Hopital de L’Archet Service des Maladies Infectieuses, Nice,
France), Jean-Michel (Livrozet, Hopital Edouard Herriot Pav-
illon P du Pr. Touraine, Lyon Cedex, France), Anne Simon
(Groupe Hospitalier Pitie-Salpetriere Service de Medecine In-
terne, Paris Cedex, France), Laurent Hocqueloux (CHR La
Source Medecine, Orleans, France), MyriamKirstetter(Cabinet
Medical, Paris, France), Gerard Lepeu (Centre Hospitalier
Henri Duffaut, Service des Maladies Infectieuses, Avignon
Cedex, France), Robert Colebunders (Instituut Voor Tropische
Geneeskunde, Antwerpen, Belgium), Nathan Clumeck (Centre
Hospitalier Universitaire Saint-Pierre, Division Infectious Dis-
eases, Bruxelles, Belgium), Bernard Vandercam (Cliniques
Antonio Ocampo (Hospital Xeral De Vigo Pizarro,Pontevedra,
Spain), and Jose Aldeguer (Lopez, Hospital Universitario La Fe
Avda, Valencia, Spain).
data supplied by Bristol-Myers Squibb and requesting additional data or
analysis when necessary. i3 Statprobe (Ann Arbor, MI) provided assistance
in preparing and editing this article.
Bristol-Myers Squibb, the manufacturer of ataza-
navir, sponsored the trial and collected and analyzed the data.
Potential conflicts of interest.
J.M.G. has received research grants or
honoraria for lectures or for participation in advisory boards from Bristol-
Myers Squibb, Gilead Sciences, Roche, Abbott, GlaxoSmithKlein, Tibotec,
Virco, Boehringer Ingelheim, Pfizer, and Sanofi Pasteur. C.L. has received
The article waspreparedbytheauthorsusing
research grants or honoraria for lectures or for participation in advisory
boards from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb,
GlaxoSmithKline, Gilead Sciences, Pfizer, Jansen-Cilag, and Roche. All
other authors: no conflicts.
1. Saraceni V, da Cruz MM, Lauria Lde M, et al. Trendsandcharacteristics
of AIDS mortality in the Rio de Janeiro city after the introduction of
highly active antiretroviral therapy. Braz J Infect Dis 2005;9:209–15.
2. Stone VE. Strategies for optimizing adherence to highly active anti-
retroviral therapy: lessons from research and clinical practice. Clin
Infect Dis 2001;33:865–72.
3. Chesney M. Adherence to HAART regimens. AIDS Patient Care STDS
4. Scott JD. Simplifying the treatment of HIV infection with ritonavir-
boosted protease inhibitors in antiretroviral-experienced patients. Am
J Health Syst Pharm 2005;62:809–15.
5. Moyle G. The Assessing Patients’ PreferredTreatments(APPT-1)study.
Int J STD AIDS 2003;14(Suppl 1):34–6.
6. Barrios A, Negredo E, Domingo P, et al. Simplification therapy with
once-daily didanosine, tenofovirandefavirenzinHIV-1-infectedadults
with viral suppression receiving amorecomplexantiretroviralregimen:
final results of the EFADITE trial. Antivir Ther 2005;10:825–32.
7. Squires K, Lazzarin A, Gatell JM, et al. Comparison of once-daily
atazanavir with efavirenz, each in combination with fixed-dose zido-
vudine and lamivudine, as initial therapy for patients infected with
HIV. J Acquir Immune Defic Syndr 2004;36:1011–9.
8. Murphy RL, Sanne I, Cahn P, et al. Dose-ranging, randomized,clinical
trial of atazanavir withlamivudineandstavudineinantiretroviral-naive
subjects: 48-week results. AIDS 2003;17:2603–14.
9. Johnson M, Grinsztejn B, Rodriguez C, et al. 96-week comparison of
once-daily atazanavir/ritonavir and twice-daily lopinavir/ritonavir in
patients with multiple virologic failures. AIDS 2006;20:711–8.
10. Expert panel on detection, evaluation, and treatment of high blood
cholesterol in adults. Executive summary of the third report of the
National Cholesterol Education Program (NCEP) expert panel on de-
tection, evaluation, and treatment of high blood cholesterol in adults
(Adult Treatment Panel III). JAMA 2001;285:2486–97.
11. Cohen C, Nieto-Cisneros L, Zala C, et al. Comparison of atazanavir
with lopinavir/ritonavirin patientswithpriorproteaseinhibitorfailure:
a randomized multinational trial. Curr Med Res Opin 2005;21:
12. Mobius U, Lubach-Ruitman M, Castro-Frenzel B, et al. Switching to
atazanavir improves metabolic disorders in antiretroviral-experienced
patients with severe hyperlipidemia. J Acquir Immune Defic Syndr
13. Wood R, Phanuphak P, Cahn P, et al. Long-term efficacy and safety
of atazanavir with stavudine and lamivudine in patients previously
treated with nelfinavir or atazanavir. J Acquir Immune Defic Syndr
14. Haas DW, Zala C, Schrader S, et al. Therapy with atazanavir plus
saquinavir in patients failing highly active antiretroviral therapy: aran-
domized comparative pilot trial. AIDS 2003;17:1339–49.
15. Gatell JM, Branco T, Sasset L, et al. Efficacy and safety of atazanavir
(ATV) based HAARTin virologicallysuppressedsubjectsswitchedfrom
lopinavir/ritonavir (LPV/RTV) treatment[abstractThPe0123].In:Pro-
gram and abstracts of the 16th International AIDS Conference, 13–18
August, 2006. Toronto, Canada: International AIDS Society, 2006.
by guest on December 22, 2015