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Benefit of treatment interruption in HIV-infected
patients with multiple therapeutic failures: a randomized
controlled trial (ANRS 097)
Christine Katlama
a
, Ste ´ phanie Dominguez
a
, Karine Gourlain
b
,
Claudine Duvivier
a
, Constance Delaugerre
b
, Mayeule Legrand
a
,
Roland Tubiana
a
, Jacques Reynes
c
, Jean-Michel Molina
d
,
Gilles Peytavin
e
, Vincent Calvez
b
, and Dominique Costagliola
a
Background: Both highly potent antiretroviral drug rescue therapy and treatment inter-
ruption have been suggested to be effective in patients with multiple treatment failure.
Objective: To assess both the benefits and risks of an 8-week treatment interruption
associated with a six to nine-drug rescue regimen in patients with multiple treatment
failures.
Design: A randomized comparative controlled trial in 19 university hospitals in France.
Patients: Sixty-eight HIV-infected patients with multiple previous treatment failures
and CD4 cell counts less than 200 3 10
6
cells/l and plasma HIV-1-RNA levels of
50 000 copies/ml or greater.
Measurements: The primary efficacy outcome was the proportion of patients with at
least a 1 log
10
decrease (copies/ml) in the plasma HIV-1-RNA level after 12 weeks of
therapy.
Results: Treatment interruption followed by multidrug salvage therapy led to a greater
proportion of patients achieving virological success (i.e. 1 log
10
decrease) at 12 weeks
compared with patients receiving multidrug therapy alone (62 versus 26%, intent-to-
treat analysis; P ¼ 0.007). The median decrease in the HIV-1-RNA level was 1.91
and 0.37 log
10
copies/ml (P ¼ 0.008), respectively. Treatment interruption led to an
increase in the number of sensitive drugs of the multidrug regimen (71 versus 35% of
regimen with at least two sensitive drugs; P ¼ 0.004). Factors associated with virologi-
cal success were treatment interruption, the reversion of at least one mutation to wild
type, adequate plasma drug concentration, and the use of lopinavir.
Conclusion: Treatment interruption was beneficial for treatment-experienced HIV-
infected patients with advanced HIV disease and multidrug-resistant virus.
& 2004 Lippincott Williams & Wilkins
AIDS 2004, 18:217–226
Keywords: HIV, salvage therapy, treatment failure, treatment interruption
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
From the
a
De ´partement des Maladies Infectieuses et Tropicales/INSERM E 0214, and
b
Laboratoire de Virologie, Ho ˆ pital Pitie ´-
Salpe ˆtrie `re, 47–83 Boulevard de l’Ho ˆpital, 75651 Paris Cedex 13, France;
c
Service des Maladies Infectieuses, Ho ˆ pital Guy de
Chauliac, 80 Avenue Augustin Fliche, 34295 Montpellier cedex 5, France;
d
Service des Maladies Infectieuses, Ho ˆ pital Saint-
Louis, 1 Avenue Claude Vellefaux, 75475 Paris cedex 10, France; and
e
Laboratoire de Pharmacologie, Hopital Bichat-Claude
Bernard, 47 rue Henri Huchard, 75877 Paris Cedex 18, France.
Correspondence to: Christine Katlama, Departement des Maladies Infectieuses, Ho ˆ pital Pitie ´-Salpe ˆtrie `re, 47 Boulevard de
l’Ho ˆpital, 75013 Paris, France.
Tel: +33 1 42 16 01 30/42; fax: +33 1 42 16 01 26; e-mail: christine.katlama@psl.ap-hop-paris.fr
Received: 19 February 2003; revised: 24 June 2003; accepted: 7 July 2003.
DOI: 10.1097/01.aids.0000111376.01109.06
ISSN 0269-9370 & 2004 Lippincott Williams & Wilkins
217