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Benefit of treatment interruption in HIV-infected patients with multiple therapeutic failures: a randomized controlled trial (ANRS 097)

Katlama, Christinea; Dominguez, Stéphaniea; Gourlain, Karineb; Duvivier, Claudinea; Delaugerre, Constanceb; Legrand, Mayeulea; Tubiana, Rolanda; Reynes, Jacquesc; Molina, Jean-Micheld; Peytavin, Gillese; Calvez, Vincentb; Costagliola, Dominiquea

Clinical Science

Background: Both highly potent antiretroviral drug rescue therapy and treatment interruption 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 × 106 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 log10 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 log10 decrease) at 12 weeks compared with patients receiving multidrug therapy alone (62 versus 26%, intent-to-treat analysis; P = 0.007). The median decrease in the HIV-1-RNA level was −1.91 and −0.37 log10 copies/ml (P = 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 = 0.004). Factors associated with virological 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.

From the aDépartement des Maladies Infectieuses et Tropicales/INSERM E 0214, and bLaboratoire de Virologie, Hôpital Pitié-Salpêtrière, 47–83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France; cService des Maladies Infectieuses, Hôpital Guy de Chauliac, 80 Avenue Augustin Fliche, 34295 Montpellier cedex 5, France; dService des Maladies Infectieuses, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75475 Paris cedex 10, France; and eLaboratoire de Pharmacologie, Hopital Bichat-Claude Bernard, 47 rue Henri Huchard, 75877 Paris Cedex 18, France.

Correspondence to: Christine Katlama, Departement des Maladies Infectieuses, Hôpital Pitié-Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.

Tel: +33 1 42 16 01 30/42; fax: +33 1 42 16 01 26; e-mail:

Received: 19 February 2003; revised: 24 June 2003; accepted: 7 July 2003.

© 2004 Lippincott Williams & Wilkins, Inc.