Clinical trial NCT00140751: Comparison of Treatment Simplification by LPV/r vs Current Treatment Continuation in HIV-Infected Patients
Official title: A 48-Weeks National Multicenter Randomized Open Clinical Trial Evaluating Tolerance and Efficacy of a Treatment Simplification by Lopinavir/Ritonavir Versus Continuation of Current Treatment in HIV-Infected Patients With a Viral Load Inferior to 50 Copies/mL Since 6 Months At Least
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV-1
Treatment simplification
Lopinavir/ritonavir
Treatment Experienced
HIV Seropositivity
Lead sponsor: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2005-09-01
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the efficacy and tolerance of a treatment simplification by a Lopinavir/ritonavir monotherapy versus continuation of current treatment in HIV-infected patients

Detailed description: Highly active antiretroviral therapy (HAART) has made a significant impact on the natural history of HIV-1 infection, but toxicities and complexities of therapy limit long-term efficacy, and make simpler yet effective HAART regimens highly desirable. Previous attempts to 'de-intensify' protease inhibitor (PI)-based therapy by discontinuing reverse transcriptase inhibitors (RTI) after achieving viral suppression met with failure, probably because plasma levels of most individually administered PI are too low to inhibit viral replication consistently.

Low-dose ritonavir substantially enhances lopinavir plasma levels, and lopinavir/ritonavir (LPV/r) is effective as part of a combination therapy in both naive and PI-experienced patients. Furthermore, lopinavir is known to have a high genetic barrier to selection of resistance. LPV/r monotherapy could thus have the right combination of potency, favorable pharmacokinetics, and high genetic barrier needed to suppress viral replication and prevent the selection of lopinavir resistance. Preliminary results with "maintenance"LPV/r monotherapy show interesting results but data from randomized studies are needed.

Eligibility criteria: Inclusion Criteria:

* Age \> or = 18 years
* Confirmed HIV-1 seropositivity
* Antiretroviral treatment stable since 3 months at least
* HIV-1 ARN load \< 50 copies/mL since 6 months at least
* Signed consent form
* No history of treatment failure (= viral load \> 1000 copies/mL) including a protease inhibitor
* No opportunistic infection in the previous 6 months

Exclusion Criteria:

* Neutrophils \< 750/mm3
* Hemoglobin \< 8 g/dL
* Platelets \< 60,000/mm3
* Creatinin \> 150 micromoles/L
* SGOT \> 5 NUL (Normal Upper Limit)
* SGPT \> 5 NUL
* Current IL-2 treatment
* HBV infection treated or not by lamivudine or tenofovir
* Pregnancy or feeding
* Enrollment in another study not compliant with KALESOLO Study group assignment

Primary outcomes:
measure: Percentage of patients with a viral load < 50 copies/mL at S48 without any modification of antiretroviral treatment during study
timeFrame: W48
Secondary outcomes:
measure: Durability of viral response
timeFrame: W48
measure: Evolution of lymphocytes CD4
timeFrame: W48
measure: Observance
timeFrame: W48
measure: Clinical and biological tolerance
timeFrame: W48
measure: Quantitative and qualitative changes in quality of life data
timeFrame: W48
measure: Cost-efficacy ratio
timeFrame: W48
measure: Predictive value of proviral DNA before treatment simplification
timeFrame: W48
measure: Proportion of patients showing a lipodystrophy at J0 and S48
timeFrame: W48
Other outcomes:
Locations:
city: Fort-de-France
country: France
facility: Hôpital Pierre Zobda-Quitman - Service de Maladies Infectieuses et Tropicales
state: Martinique
city: Annecy
country: France
facility: Centre Hospitalier de la Région Annecienne (CHRA) - Service d'Infectiologie
city: Bondy
country: France
facility: Hôpital Jean Verdier - Unité de Maladies Infectieuses
city: Bordeaux
country: France
facility: Hôpital Pellegrin - Service de Médecine Interne et Maladies Infectieuses
city: Bordeaux
country: France
facility: Hôpital Saint-André - Service de Médecine Interne et Maladies Infectieuses
city: Bordeaux
country: France
facility: Hôpital Saint-André - Service de Médecine Interne et Maladies Tropicales
city: Caen
country: France
facility: Hôpital Côte de Nacre - Service des Maladies Infectieuses
city: Créteil
country: France
facility: Hôpital Henri Mondor - Service d'Immunologie Clinique
city: Garches
country: France
facility: Hôpital Raymond Poincaré - Service des Maladies Infectieuses et Tropicales
city: Grenoble
country: France
facility: Hôpital A. Michallon - Service des Maladies Infectieuses
city: Le Kremlin-Bicetre
country: France
facility: Hôpital Bicêtre - Service de Médecine Interne
city: Marseille
country: France
facility: Hôpital Nord - CISIH
city: Marseille
country: France
facility: Hôpital Sainte-Marguerite - Unité Médicale CISIH
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac - Service de Maladies Infectieuses et Tropicales
city: Nice
country: France
facility: Hôpital de l'Archet - Service d'Infectiologie
city: Paris
country: France
facility: Hôpital Saint-Antoine - Service des Maladies Infectieuses et Tropicales
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpêtrière - Service de Maladies Infectieuses et Tropicales
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpêtrière - Service de Médecine Interne 1
city: Paris
country: France
facility: Hôpital-Fondation Saint-Joseph - Service des Maladies Infectieuses
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou (HEGP) - Département d'Immunologie
city: Paris
country: France
facility: Hôpital Tenon - Service des Maladies Infectieuses et Tropicales
city: Rennes
country: France
facility: Hôpital Pontchaillou - Service des Maladies Infectieuses
city: Strasbourg
country: France
facility: Hôpital Civil - Hôpital de Jour du CISIH - Clinique Médicale A
city: Tourcoing
country: France
facility: Hôpital Gustave Dron - Service des Maladies Infectieuses
city: Vandoeuvre-les-Nancy
country: France
facility: Hôpital de Brabois Adultes - Service de Maladies Infectieuses et Tropicales
Study officials:
affiliation: Hôpital Saint-Antoine - Service des Maladies Infectieuses et Tropicales (Paris, France)
name: Jean-Luc MEYNARD, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, d'Arminio Monforte A, Knysz B, Dietrich M, Phillips AN, Lundgren JD; EuroSIDA study group. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet. 2003 Jul 5;362(9377):22-9. doi: 10.1016/s0140-6736(03)13802-0.
citation: Yeni PG, Hammer SM, Hirsch MS, Saag MS, Schechter M, Carpenter CC, Fischl MA, Gatell JM, Gazzard BG, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Schooley RT, Thompson MA, Vella S, Volberding PA. Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA Panel. JAMA. 2004 Jul 14;292(2):251-65. doi: 10.1001/jama.292.2.251.
citation: Bartlett JA, DeMasi R, Quinn J, Moxham C, Rousseau F. Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults. AIDS. 2001 Jul 27;15(11):1369-77. doi: 10.1097/00002030-200107270-00006.
citation: Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60. doi: 10.1056/NEJM199803263381301.
citation: Murphy R, Gazzard B. Antiretroviral treatment guidelines. AIDS. 2003 Jun;17 Suppl 2:S1. doi: 10.1097/00002030-200306002-00001. No abstract available.
citation: Bucher HC, Kofler A, Nuesch R, Young J, Battegay M, Opravil M. Meta-analysis of randomized controlled trials of simplified versus continued protease inhibitor-based antiretroviral therapy in HIV-1-infected patients. AIDS. 2003 Nov 21;17(17):2451-9. doi: 10.1097/00002030-200311210-00007.
citation: Drechsler H, Powderly WG. Switching effective antiretroviral therapy: a review. Clin Infect Dis. 2002 Nov 15;35(10):1219-30. doi: 10.1086/343050. Epub 2002 Oct 21.
citation: Martinez E, Conget I, Lozano L, Casamitjana R, Gatell JM. Reversion of metabolic abnormalities after switching from HIV-1 protease inhibitors to nevirapine. AIDS. 1999 May 7;13(7):805-10. doi: 10.1097/00002030-199905070-00009.
citation: Moyle G, Baldwin C, Mandalia S, Comitis S, Burn P, Gazzard B. Changes in metabolic parameters and body shape after replacement of protease inhibitor With efavirenz in virologically controlled HIV-1-positive persons: single-arm observational cohort. J Acquir Immune Defic Syndr. 2001 Dec 1;28(4):399-401. doi: 10.1097/00126334-200112010-00016. No abstract available.
citation: Lambert-Niclot S, Grude M, Meynard JL, Marcelin AG, Valantin MA, Flandre P, Izopet J, Moinot L, Bouteloup V, Calvez V, Katlama C, Girard PM, Morand-Joubert L. Ultrasensitive Human Immunodeficiency Virus Type 1 Viral Load as a Marker of Treatment Choice for Simplification Strategies. Clin Infect Dis. 2018 Nov 28;67(12):1883-1889. doi: 10.1093/cid/ciy382.
citation: Meynard JL, Bouteloup V, Landman R, Bonnard P, Baillat V, Cabie A, Kolta S, Izopet J, Taburet AM, Mercie P, Chene G, Girard PM; KALESOLO Study Group. Lopinavir/ritonavir monotherapy versus current treatment continuation for maintenance therapy of HIV-1 infection: the KALESOLO trial. J Antimicrob Chemother. 2010 Nov;65(11):2436-44. doi: 10.1093/jac/dkq327. Epub 2010 Sep 15.