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 (ANRS CO18)

ANRS HIV CONTROLLERS NATIONAL OBSERVATORY

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Biological: blood test at day one

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.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Kremlin Bicêtre, France

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: patient	Biological: blood test at day one; Epidemiological, clinical, virological, and immunological data will be collected. Clinical events as neoplasia will be collected

What is the study measuring?

Primary Outcome Measures

Outcome Measure
to allow the long-term follow-up of the HIV controllers. Epidemiological, clinical, virological, and immunological data will be collected.

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: February 8, 2010
• First Submitted That Met QC Criteria: February 8, 2010
• First Posted (Estimate): February 9, 2010

Study Record Updates

• Last Update Posted (Estimate): December 27, 2012
• Last Update Submitted That Met QC Criteria: December 26, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: 05-0222