Clinical trial NCT01065207: Patients Infected With HIV Since More Than 10 Years With a Plasma Viral RNA <400 Copies / mL in the Absence of Any Treatment: Study Mechanisms Involved in Controlling the Infection
Official title: ANRS HIV CONTROLLERS NATIONAL OBSERVATORY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infection
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2010-02-09
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The investigators have previously described a limited group of HIV-1-infected patients, we called HIV controllers (HIC), who have been infected for more than 10 years, in whom viral replication is spontaneously controlled without any treatment. These patients are defined according to virological criteria: more than 90% of the quantifications of plasma viral load should be less than 400 RNA copies/mL. The purpose of the ANRS EP36 study was to characterize these patients.

Detailed description: To study the virological and immunological features of these patients, a consortium of research teams has been set up. Several results were obtained (cf publications) : HIC are infected with replication-competent virus, HIV infects HIC CD4 T cells ex vivo but the CD8 T cells fully control this viral replication. This study led to set up a national observatory of the HICs. This observatory, set up from May 2006 to May 2008, has allowed to identify and include 86 HIC patients in France (about one hundred had been reported by the ANRS centers). When a patient is included, clinical data are collected and a biologic collection set up which can be used in genomic studies. The main characteristics of the patients included in the observatory are a median age at the diagnosis of HIV infection of 29 years (range 1-49), a median age at inclusion of 45 years \[19-78\], 42% are women, 87% are caucasians. The median year of HIV diagnosis is 1989 (1983-1999), so a median of 18 years of known HIV infection. The CD4 median between 1986 and 2008 is 762 CD4/mm3 \[IQR:589-962\], 3% of the 1368 measures are ≤ 350 /mm3; 23% patients have a CD4 T cell count \< 500/mm3 and 6% \< 350/mm3 at the inclusion consultation. The CD4 slope on this period shows a slow decrease estimated to -13 \[-15,-11\] CD4/mm3 per year. Between 1989 and 2007, 2% of the viral loads measured were ≥ 1000 RNA copies/mL. The viral load at inclusion is \> 400 RNA copies/mL in 4%. Median viral DNA at the inclusion in the observatory is 1, 75 \[1, 44-2, 07\] log copies/millions PBMC.

The transformation of the observatory in a cohort CO 18 has several goals. The first one is to allow the long-term follow-up of the HIV controllers. Epidemiological, clinical, virological, and immunological data will be collected. The outcome of these patients is a major question: some patients could loose their HIC status either because of a drop in their CD4 T cell counts to a level below 200/mm3 without major viral replication or because viral replication becomes detectable. To understand the mechanisms involved in the control of the viral replication in HIC implies to study the patients in whom the viral control is lost and to compare them to the HIC in whom the control is preserved. Therefore it is of major importance to follow the patients now included in the observatory during a prolonged time. To increase the frequency of loss of control, the patients in whom the virus is controlled for at least 5 years but for less than 10 years will be included to increase the diversity of the HICs. Clinical events as neoplasias will be collected. The genomic studies will be continued with the benefits of new inclusions and european collaborations will be developed. The question of the quality-of-life of the patients HIC will be studied.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* able to give written consent
* who have been infected for more than 5 years
* not treated by ARV
* HIV positive serology
* Covered by French Social Security

Exclusion Criteria:

* Non compliance with the criteria of inclusion
* Pregnancy (inclusion can be postponed)
* Covered by French Social Security

Primary outcomes:
measure: to allow the long-term follow-up of the HIV controllers. Epidemiological, clinical, virological, and immunological data will be collected.
Secondary outcomes:
measure: To understand the mechanisms involved in the control of the viral replication in HIC implies to study the patients in whom the viral control is lost and to compare them to the HIC in whom the control is preserved
Other outcomes:
Locations:
city: Kremlin Bicêtre
country: France
Study officials:
affiliation: CH Belfort
name: JP Faller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Poitiers
name: Pascal Roblot, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Pointe à Pitre
name: Gilles Beaucaire, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Robert Debré REIMS
name: Christine Rouger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHI Ballanger Aulnay sous Bois
name: Jean Luc Delassus, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Gilles De Corbeil Corbeil
name: Alain Devidas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital St Louis Paris
name: Louis Bubertet
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Avicenne BOBIGNY
name: Michèle Bentata, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Hotel Dieu Paris
name: Alexandra Compagnucci, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Victore Dupouy Argenteuil
name: Philippe Genet, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHI Villeneuve St Goerges
name: Olivier Patey, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU St Jacques Besancon
name: Marie Christine Drobacheff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Minjoz Besanson
name: Helder Gil, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital St Louis Paris
name: Eric Oksenhendler, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Bellevue St Etienne
name: Frédéric Lucht, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Pellegrin Bordeaux
name: Michel Dupon, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Nord Amiens
name: Jean Luc Schmit, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St Louis ¨Paris
name: Daniel Sereni, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hotel Dieu Paris
name: JP Viard, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH Annecy
name: JP Bru, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Le Kremlin Bicetre
name: JF Delfraissy, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH Henri Duffaut Avignon
name: Gilles Pichancourt
role: PRINCIPAL_INVESTIGATOR
affiliation: CH du payx d'Aix
name: André Pierre Blanc, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Chalucet Toulon
name: Alain Lafeuillade, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Inter Armées Bégin St Mandé
name: Christophe Rapp, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Raymond Pointcarré Garches
name: Pierre De Truchis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Jean Verdier Bondy
name: Vincent Jeantils, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Paul Brousse Villejuif
name: Daniel Vittecoq, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Tenon Paris
name: Gilles Pialoux, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Avicenne Bobigny
name: Olivier Bouchaud, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Antoine Béclère Clamart
name: Francois Boué, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: HEGP Paris
name: Laurence Weiss, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cochin
name: Dominique Salmon Ceron, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Foch Suresnes
name: Olivier Bletry, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Louis Mourier Paris
name: Emmanuel Mortier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Henri Mondor Créteil
name: Alain Sobel, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pitié Salpétrière Paris
name: Christine Katlama, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pitié Salpétrière Paris
name: Anne Simon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St Antoine Paris
name: Pierre Marie Girard, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: St Louis Paris
name: JM Molina, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Pierre Zobda Quitman Fort de France
name: André Cabié, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Angers
name: JM Chennebault, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital St André Bordeaux
name: Philippe Morlat, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Limoges
name: Pierre Weinbreck, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Edouard Herriot - Lyon
name: JL Tourraine, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Hotel Dieu Lyon
name: Christian Trépo, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ste Marguerite Marseille
name: Isabelle Poizot Martin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Bichat, Paris
name: Sophie Matheron, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Hotel Dieu Nantes
name: François Raffi, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH La Roche sur Yon
name: Philippe Perré, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital l'Archet Nice
name: Pierre Delomonica, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital l'Archet Nice
name: Eric Rosenthal, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rennes University Hospital
name: Christian Michelet, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Strasbourg
name: David Rey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Bretonneau Tours
name: JM Besnier, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Purpan (Toulouse)
name: Bruno Marchou, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital de la côte de Nacre Caen
name: Renaud Verdon, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Hotel Dieu Clermont Ferrand
name: Christine Jacomet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Dijon
name: Lionel Piroth, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Albet Michallon Grenoble
name: Pascale Leclercq, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Gustave Dron Tourcoing
name: Yazdan Yazdanpanah, PHD
role: STUDY_DIRECTOR
affiliation: Hopital de Brabois Nancy
name: Thierry May, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: chu Rouen
name: Francois Caron, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: St André Bordeaux
name: Patrick Mercié, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Pellegrin Bordeaux
name: Claire Series, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH Bourg en Bresse
name: Philippe Granier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH rené Arbeltier Coulomniers
name: Marc Gatfosse, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Groupe Hospitalier Sud Reunion St Pierre de la Réunion
name: Patrice Poubeau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Beaujon Clichy
name: Agnès Uludag, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHR Orléans
name: Philippe Arsac, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH intercommunal Créteil
name: Isabelle Delacroix, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CASH Nanterre
name: Vincent Daneluzzi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Ambroise Paré Boulogne
name: Elisabeth Rouveix, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH Noyon
name: Goerges Diab, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH Mulhouse
name: Geneviève Berck Wirth
role: PRINCIPAL_INVESTIGATOR
affiliation: CHI Les hopitaux du Léman Thonon les Bains
name: Philippe Romand, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital René Dubois Pontoise
name: Laurent Blum, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH St Nazaire
name: Christophe Michau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHI Fréjus St Raphaël
name: Raymond Armero, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Notre Dame de Bon Secours Metz
name: Bernard Christian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Beauregard Thionville
name: Philippe Muller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH Bretagne Atlantique Vannes
name: Henri Jardel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Simone Weil Eaubonne
name: Elisabeth Carbonnel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital La source Orléans
name: Laurent Hocqueloux, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH Juvisy sur Orge
name: Marie Odile Lemaitre, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Ambroise Paré Marseille
name: Patrick Philibert, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Pasteur Paris
name: Paul Henry Consigny, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Pellegrin Bordeaux
name: JM Ragnaud, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Joseph Ducuing Toulouse
name: Daniel Garipuy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU St Brieuc
name: Beuscart MD Claude
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Simone Veil - Eaubonne
name: Leprêtre MD Annie
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Pasteur Paris
name: Duvivier MD Claudine
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Joseph Ducuing Toulouse
name: Garipuy MD Daniel
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre hospitalier de Perpignan
name: Aumaitre MD Hugues
role: PRINCIPAL_INVESTIGATOR
affiliation: Lariboisière Paris
name: Rami MD Agathe
role: PRINCIPAL_INVESTIGATOR
affiliation: CH Général Montauban
name: De Lavassière MD Marc
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Croix Rousse Lyon
name: Miailhes MD Patrick
role: PRINCIPAL_INVESTIGATOR
References: