assemblee generale 21 janvier 2011

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assemblee generale 21 janvier 2011
 ASSEMBLEE GENERALE 5 AVRIL 2013
•
ANRS CO 01 - Etude prospective multicentrique de la transmission materno-fœtale du VIH1 et/ou
du VIH2 et de sa prévention
PROMOTEUR : Agence Nationale de Recherches sur le Sida (ANRS)
INVESTIGATEUR PRINCIPAL
Dr Josiane WARSZAWSKI (épidémiologiste), CESP - INSERM U1018, Hôpital Bicêtre
CO-INVESTIGATEURS
Pr Laurent MANDELBROT (obstétricien), Hôpital Louis Mourier
Dr Roland TUBIANA (infectiologue), Hôpital Pitié Salpétrière
Pr Stéphane BLANCHE (pédiatre), Hôpital Necker Enfants Malades
•
ANRS CO 10 – Cohorte d’enfants infectés par le VIH
PROMOTEUR : Agence Nationale de Recherches sur le Sida (ANRS)
INVESTIGATEUR PRINCIPAL
Dr Josiane WARSZAWSKI (épidémiologiste), CESP - INSERM U1018, Hôpital Bicêtre
CO-INVESTIGATEURS
Dr Catherine DOLLFUS (pédiatre), Hôpital Trousseau
Pr Albert FAYE (pédiatre), Hôpital Robert Debré
•
ANRS CO 11 – Observatoire des enfants nés de mère séropositive
INVESTIGATEUR PRINCIPAUX
Dr Josiane WARSZAWSKI (épidémiologiste), CESP - INSERM U1018, Hôpital Bicêtre
Pr Stéphane BLANCHE (pédiatre), Hôpital Necker Enfants Malades
•
ANRS CO 19 – Coverte (Cohorte d’Enfants Infectés par voie verticale et dans l’enfance)
PROMOTEUR : Agence Nationale de Recherches sur le Sida (ANRS)
INVESTIGATEUR PRINCIPAL
Dr Josiane WARSZAWSKI (épidémiologiste), CESP - INSERM U1018, Hôpital Bicêtre
CO-INVESTIGATEUR
Dr Jean-Paul VIARD, Hôpital Hôtel Dieu
•
ANRS 145 – Primeva
PROMOTEUR : Agence Nationale de Recherches sur le Sida (ANRS)
INVESTIGATEUR PRINCIPAL
Dr Roland TUBIANA (infectiologue), Hôpital Pitié Salpétrière
RESPONSABLE METHODOLOGIQUE
Dr Josiane WARSZAWSKI (épidémiologiste), CESP - INSERM U1018, Hôpital Bicêtre
•
ANRS EP38 – Immip
PROMOTEUR : Agence Nationale de Recherches sur le Sida (ANRS)
INVESTIGATEUR PRINCIPAL
Pr Stéphane BLANCHE (pédiatre), Hôpital Necker Enfants Malades
RESPONSABLE SCIENTIFIQUE
Florence BUSEYNE (Immunologiste), Institut Pasteur
RESPONSABLE METHODOLOGIQUE
Dr Josiane WARSZAWSKI (épidémiologiste), CESP - INSERM U1018, Hôpital Bicêtre
VIROLOGIE : Pr Christine Rouzioux, Hôpital Necker, Paris
CESP Inserm U 1018
Hôpital de Bicêtre - Secteur "Lasjaunias" - Porte 76
82, rue du Général Leclerc
94276 Le Kremlin-Bicêtre
Tél. 01 49 59 53 10 - Fax 01 49 59 53 00
E-mail [email protected]
http://u822.kb.inserm.fr/epf
EQUIPE DE COORDINATION
CESP 1018 / Equipe 4
Hôpital Bicêtre
„ Coordination
Naïma Bouallag (EPF, Immip), Sandrine Delmas (Primeva), Nelly Briand (Coverte)
„ Monitorage, codage
Souad Belaggoun, Lila Hamadou, Julie Lamarque, Jacques N’Gondi, Anais Perilhou,
Marine Pytkowski, Rihab Rais
„ Datamanagement et organisation logistique des études
Céline Ferey, Corinne Laurent, Elisa Ramos, Thierry Wack
„ Saisie, mise à jour, archivage
Leila Boufassa, Paulette Huyhn
„ Epidémiologistes, statisticiens, informaticiens
Nelly Briand, Jérôme Le Chenadec, Jean-Paul Teglas, Josiane Warszawski
„ Secrétariat
Marlène Péres
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ENQUETE PERINATALE FRANCAISE
ANRS - CO1/CO10/CO11
Sites participants
APHP Hôpital Louis Mourier, Colombes, France (Laurent Mandelbrot*, Françoise Meier, Dominique Duro,
Marine Joras, Emmanuel Mortier, Catherine Crenn-Hebert, Corinne Floch-Tudal*, Fabienne Mazy, Isabelle Cahite,
Anne-Marie Simonpoli, Catherine Branger, Anne-Véronique Kah Samba, Houria Ichou, Laurence Marty, Catherine
Buffamene, Catherine Briquet, Lyne Melgrani); APHP Hôpital Beaujon, Clichy, France (Maria Banige, Mariam
Bensalah, Pierre-François Ceccaldi*, Carine Davitian, Agnès Lefort, Dominique Luton, Ali Tadlaoui, Agnès
Villemant-Uludag, Virginie Zarrouk); Hôpital Sainte Musse, Toulon, France (Gisèle Philip, Gilles Hittinger*);
CHG Marechal Joffre, Perpignan, France (Martine Malet, Bruno Bachelard, Marie Medus*); CHU Caremeau,
Nîmes, France (Joëlle Dendale-Nguyen*, Nadine Bouenel, Fréderic Grosjean); CHD les Oudairies, La Roche sur
Yon, France (Jean-Pierre Brossier, Olivier Aubry, Jean-Luc Esnault, Sophie Leautez, Philippe Perré*, Isabelle
Suaud); Centre Hospitalier William Morey, Châlon sur Saone, France (Sandrine-Anne Martha*); Centre
Hospitalier, Vernon, France (Mahfoud Rouha); Centre Hospitalier Intercommunal de Cornouaille, Quimper, France
(Pascale Perfezou*, Gilles Blondin, Charles Bellot); Centre Hospitalier Universitaire, Brest, France (Séverine
Ansart*, Philippe Le Moine, Karine Bages-Jaffuel, Jean-Charles Duthé, Michel Garré, Sylvain Jaffuel); Centre
Hospitalier, St Brieuc, France (Corinne Daniel*, Christian Calvez, Claude
Beuscart, Emmanuelle Boutaric,
Jennifer Rohan, Sylvie Lemoal); Centre Hospitalier Universitaire, Rennes, France (Linda Lassel, Ghislaine Cotten,
Christelle Dupré, Esther Beauville, Cédric Arvieux*); Centre Hospitalier Bretagne Atlantique, Vannes, France
(Anabèle Dos Santos*, Corinne Cudeville, Yves Poinsignon, Virginie Mouton-Rioux, Gaétane Mousset, Anne
Grellier); Centre Hospitalier de Bretagne Sud, Lorient, France (Philippe Moreau, Philippe Tillaut, Virginie
Mouton-Rioux, Odile Luycx-Vaillant, Philippe de Morel, Marie-Françoise Le Coz, Isabelle Belzic, Mathilde
Niault*); Centre Hospitalier de la région d’Annecy, Annecy, France (Anne Vandenbergh, Cécile Janssen, Susanne
Braig, Virginie Vitrat*, Jacques Gaillat, Gaëlle Clavere, Jean-Pierre Bru, Blandine Peyret); Centre Hospitalier
Intercommunal, Montfermeil, France (Catherine Mullard, Marie Echard, Philippe Talon*, Marion Dehlinger);
Centre Hospitalier Intercommunal, Montreuil, France (Cécile Winter, Brigitte Heller-Roussin*); APHP Hôpital
Cochin-Port Royal, Paris, France (Odile Launay, Maria Fouchet, Ghislaine Firtion*, Isabelle Goupil, Emmanuelle
Pannier*, Nora Boudjoudi, Laurent Finkielsztejn, Marie-Laure Brival, Olivier Taulera, Danielle Rivaux); APHP
Hôpital Bichat, Paris, France (Lahcen Allal, Guylaine Alexandre, Agnès Bourgeois-Moine, Marylène Bodard,
Florence Damont, Valérie Meynckens, Gilles Peytavin, Valérie Vivier, Mandovi Rajguru, Virginie Huri, Elie
Azria, Sophie Matheron*, Neila Elaoun, Philippe Faucher); Centre Hospitalier Intercommunal, Créteil, France
(Valérie Garrait*, Christiane Komme, Isabelle Hau*, Laurent Richier, Claudine Touboul, Sophie Lemerle,
Christine Pichon, Philippe Ledudal); Hôpital de la Croix Rousse, Lyon, France (Valérie Thoirain, Laurent Cotte*,
Olivier Tariel, Joseph Koffi, Jean-Marc Labaune, Corinne Brochier, Thanh Thuy Le Thi); Centre Hospitalier
Pellegrin, Bordeaux, France (Denis Roux*, Christophe Elleau, Camille Runel*, Jacques Horovitz, Pierre
Chabanier, Yves Perel, Sandrine Delveaux, Danielle Douard); CHU Les Abymes, Pointe à Pître, France (Henri
Bataille*, Marie-Thérèse Sow, Ketty Samar, Blandine Muanza, Franck Bardinet, Anne-Claude Bodiou, Nassy
Agbetra); Centre Hospitalier Général, Creil, France (Marc Duval*, Clarisse Kingue-Ekollo, Bénédicte Carpentier);
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CHI la Seyne sur Mer, La Seyne sur Mer, France (Isabelle Ronda, Jean-Marc Chamouilli*); Hôpital de Haute
Pierre, Strasbourg, France (Natacha Entz-Werle, Bruno Langer, Françoise Uettwiller); Centre Hospitalier Général,
Longjumeau, France (Hervé Seaume*, Sarah Ducrocq, Philippe Bailly-Salin, Yvon Lemercier); Hôpital Paule de
Viguier, Toulouse, France (Joëlle Tricoire*, Alain Berrebi*, Michèle Antras, Evelyne Armand, Florence Nicot);
Centre Hospitalier de la Côte Basque, Bayonne, France (Claudine Cayla, François Bonnal, Catherine Chabanier);
Centre hospitalier intercommunal, Villeneuve St Georges, France (Isabelle Matheron, Anne Chacé); Centre
Hospitalier Intercommunal, Poissy Saint Germain en Laye, France (Sophie Couderc, Anne Boutemy*); Centre
Hospitalier Général, Fontainebleau, France (Marie-Christelle Dallot, Alain Al-Issa, Corinne Routier*); Centre
Hospitalier Robert Ballanger, Aulnay, France (Ahmed Zakaria, Véronique Favret, Juliette Gerbe, Elisabeth
Questiaux); Hôpital Civil, Strasbourg, France (Patricia Fisher, MariaLuisa Partisani*, David Rey, Christine
Cheneau); Centre Hospitalier Victor Dupouy, Argenteuil, France (Christine Allisy, Dominique Brault*); APHP
Hôpital Tenon, Paris, France (François Hervé, Marie-Gisèle Lebrette*, Lise Selleret); Centre Hospitalier Général,
Saint-Denis, France (Dieudonné Ekoukou, Pascal Bolot*, Marie-Aude Khuong-Josses, Marie-Christine Allemon,
Nelly Ghibaudo); APHP Hôpital Necker, Paris, France (Pierre Frange, Christine Rouzioux, Florence Veber,
Stéphane Blanche*, Delphine Lemercier*, Marie-Christine Mourey, Julie Galimand); Centre Hospitalier Sud
Francilien, Evry Corbeil, France (Gilles Blasquez); Centre Hospitalier Sud Francilien, Evry Corbeil, France
(Michèle Granier*, Houda Touahri, Rose Nguyen, Alain Devidas*, Adrien May, Audrey Sanchez, Claire
Malbrunot, Joëlle Neizelien, Naguib Lofty, Pierre Chevojon, Sylvie Lamiraut ); Centre Médico-Chirurgical et
Obstétrical, Schiltigheim, France (Eric David, Israël Nisand, Michèle Weil, Christophe Vayssière); CHR American
Memorial Hospital, Reims, France (Jean-Luc Berger, Martine Munzer*, Olivier Graesslin); APHP Groupe
Hospitalier Pitié Salpêtrière, Paris, France (Anne-Florence Alix-Naime, Roland Tubiana*, Frédérique Quetin, Anne
Laubies, Manuela Bonmarchand, Jennifer Sommer, Patricia Bourse, Catherine Lupin, Luminita Schneider); Centre
Hospitalier René Dubos, Pontoise, France (Anne Coursol*, Michel Youssef, Juliette Laurent); APHP Hôpital
Béclère, Clamart, France (Mariem Raho, Véronique Chambrin*, Philippe Labrune*, Laure Clech, Alexandra
Benachi); Centre Hospitalier Marc Jacquet, Melun, France (Bertrand Le Lorier*, Isolde Pauly-Ravelly); Centre
Hospitalier Général/, Evreux, France (Claude Allouche, Ama Johnson*); APHP Hôpital Jean Verdier, Bondy,
France (Laurence Benoist, Stéphanie Bolie, Anne Collignon, Catherine Delannoy, Eric Lachassine, Joël Gaudelus,
Vincent Jeantils, Isabelle Poilane, Laurence Moreau, Sylvie Sauvion, Amelie Benabara*); Centre Hospitalier de
Meaux, Meaux, France (Leïla Karaoui*, Véronique Lefèvre); CHU de l’Archet, Nice, France (André Bongain*,
Eliane Galiba, Anne Deville, Fabrice Monpoux*, Jacques Durant); Centre Hospitalier Saint Joseph, Paris, France
(Christian Aufrant*); Centre Hospitalier François Quesnay, Mantes La Jolie, France (Jean Furioli, Jean-Louis
Salomon, Françoise Granier, Antoine Doumet*); CHU Hôpital Nord, Amiens, France (Youssef Douadi, Jean
Gondry, Jean-Luc Schmit*, Brigitte Pautard); Hôpital de la Conception, Marseille, France (Marc Gamerre, Ludovic
Cravello*, Isabelle Thuret*, Katia Errichiello); CHU de Brabois-Hôpital des Adultes, Vandoeuvre les Nancy,
France (Laurence Neimann, Claire Hubert*); APHP Hôpital Trousseau, Paris, France (Bruno Carbonne*,
Geneviève Vaudre, Marie-Dominique Tabone, Catherine Dollfus*, Aurore Jensen, Jean-Marie Jouannic, JeanLouis Benifla, Mary-France Courcoux); Hôpital Charles Nicolle, Rouen, France (Didier Pinquier, Gaëlle Pinto
Cardoso*, Brigitte Clavier, Françoise Borsa-Lebas); APHP Hôpital Robert Debré, Paris, France (Agathe De
Lauzanne, Constance Borie, Christine Boissinot, Geneviève Morau, Martine Savary, Sandrine Leveillé, Albert
Faye*, Erianna Bellaton, Dominique Garion, Martine Levine*, Sophie Matheron*); APHP Hôpital de Bicêtre, Le
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Kremlin-Bicêtre, France (Claire Colmant, Cécile Goujard, Marc Tardieu, Florent Fuchs, Ikram Jrad, Delphine
Peretti*, Katia Bourdic, Corinne Fourcade*); CHRU Hôpital Saint Jacques, Besançon, France (Catherine Chirouze,
Jean-Marie Estavoyer*, Robert Maillet); CHU de Nantes, Nantes, France (Véronique Reliquet*, Norbert Winer,
Cécile Brunet*, Audrey Rodallec, Elisabeth Garnier, Edouard Vaucel , Yolande Caroit-Cambazard); CHRU
Hôpital du Bocage, Dijon, France (Isabelle Reynaud*, Claire Briandet); CHRU Hôpital Clemenceau, Caen, France
(Jacques Brouard*, Gaël Beucher, Pascale Goubin); Centre Hospitalier de Lagny, Lagny, France (Cécile Lanty,
Eric Froguel, Béatrice Gourdel, Arnaud Chalvon Demersay*, Gilbert Algava); Hôpital André Mignot, Le Chesnay,
France (Véronique Hentgen*, Fabienne Messaoudi, Nathalie Carre); CHRU de Tours, Tours, France (Pascale Nau,
Jean-Marc Besnier*, Jérôme Potin, Sophie Marchand, Zoha Maakaroun Vermesse); Institut d'Hémato-Oncologie
Pédiatrique, Lyon, France (Nadine Taché, Yves Bertrand, Kamila Kebaïli*); Hôpital Nord, Saint Etienne, France
(Véronique Ronat, Anne Fresard, Kareen Billiemaz*); Centre Hospitalier Général, Bastia, France (Ramona
Abrudan*); Centre Hospitalier Universitaire, Angers, France (Alain Fournié, Jean-Marie Chennebault*, François
Sami Rehaeim); Centre Hospitalier Régional, Orléans, France (Philippe Arsac*); APHP Hôpital Lariboisière, Paris,
France (Nicole Ciraru-Vigneron*, Geneviève Mouchnino, Dominique Ayral, Muriel Petit); CHR Arnaud de
Villeneuve, Montpellier, France (Nelly Guigue, Muriel Lalande*, Paul Benos*); Centre Hospitalier Général, Orsay,
France (Christiane De Gennes*, Sonia Chanzy, Valérie Isart, Patrick Le Fur); Centre Hospitalier de Saint Martin,
St Martin, France (François Cazassus, Véronique Walter, François Bissuel*); CHR Jeanne de Flandres, Lille ,
France (Yamina Hammou*, Laurence Bocket, Xavier Codaccioni, Sophie d'Angelo, Faïza Ajana, Françoise
Mazingue*, Françoise Taillet); CHU - Maison de la Femme et de l'Enfant, Fort de France, France (Raymond
Mezin, Yves Hatchuel*, André Cabié, William Cécile)
* Investigateur principal
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PUBLICATIONS EPF
2006 - 2013
2013
Briand N, Jasseron C, Sibiude J, Azria E, Pannier E, Pollet J, Hammou Y, Warszawski J, Mandelbrot
L.. « Cesarean section for HIV-infected women in the era of combination antiretroviral therapies:
clinical practice and mother-to-child transmission in France, 2000-2010 ».
Am J Obstet Gynecol. en révision favorable
Briand N, Warszawski J, Faye A, Le Chenadec J, Dollfus C, Teglas JP, Tubiana R, Rouzioux C,
Mandelbrot L, Blanche S, ANRS EPF study group. Is Intrapartum Prophylaxis for Mother-to-Child HIV1 Transmission Still Useful in the HAART Era?
Clin Infect Dis. en révision favorable
Rachas A, Warszawski J, le Chenadec J, Legeai C, Teglas JP, Goujard C, Rouzioux C, Mandelbrot L,
Tubiana R, Meyer L. Does Pregnancy Affect the Early Response to cART?
AIDS. 2013 Jan 28;27(3):357-67
Jasseron C, Mandelbrot L, Dollfus C, Trocmé N, Tubiana R, Teglas JP, Faye A, Rouzioux C, Blanche S,
Warszawski J. Non disclosure of a pregnant woman’s HIV status to her partner is associated with nonoptimal prevention of mother-to-child transmission.
Aids and Behavior (2013) 17:488-497
Pursuing Later Treatment Option II (PLATO II) Project Team of the Collaboration of Observational HIV
Epidemiological Research Europe (COHERE). Predictors of CD4+ T-Cell Counts of HIV Type 1-Infected
Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes.
J Infect Dis. 2013 Mar;207(5):759-67.
2012
Héraud-Bousquet V, Lot F, Esvan M, Cazein F, Laurent C, Warszawski J, Gallay A. A three-source
capture-recapture estimate of the number of new HIV diagnoses in children in France from 2003--2006
with multiple imputation of a variable of heterogeneous catchability.
BMC Infect Dis. 2012 Oct 10;12(1):251.
Chaillon A, Wack T, Braibant M, Mandelbrot L, Blanche S, Warszawski J, Barin F. The breadth and
titer of maternal HIV-1-specific heterologous neutralizing antibodies are not associated with a lower rate
of mother-to-child transmission of HIV-1.
J Virol. 2012 Oct;86(19):10540-6
Sibiude J, Warszawski J, Tibiana R, Dollfus C, Faye A, Rouzioux Ch, Teglas JP, Ekoukou D, Blanche S,
Mandelbrot L. Premature delivery in HIV-infected women starting protease inhibitor therapy during
pregnancy : role of the Ritonavir boost ?
CID 2012 May;54(9):1348-60
Goetghebuer T, Le Chenadec J, Haelterman E, Galli L, Dollfus C, Thorne C, Judd A, Keiser O, Ramos
JT, Levy J, Warszawski J ; pour The European Infrant Collaboration Group. Short and long term
immunological and virological outcome in HIV-infected infants according to the age at antiretroviral
treatment initiation.
Clin Infect Dis, 2012 ;54(6) :878-81
6
Avettand-Fenoel V, Blanche S, Le Chenadec J, Scott-Algara D, Dollfus C, Viard JP, Bouallag N,
Benmebarek Y, Riviere Y, Warszawski J, Rouzioux C, Buseyne F. Relationships between HIV disease
history and blood HIV-1 DNA in perinatally infected adolescents and young adults : the ANRS- EP38IMMIP Study.
JID 2012 May 15;205(10):1520-8
Burgard, M, S Blanche, C Jasseron, P Descamps, MC Allemon, N Ciraru-Vigneron, C Floch, B HellerRoussin, E Lachassinne, F Mazy, J Warszawski, and C Rouzioux, Performance of HIV-1 DNA or HIV-1
RNA Tests for Early Diagnosis of Perinatal HIV-1 Infection during Anti-Retroviral Prophylaxis.
J Pediatr 2012 Jan;160(1):60-6
2011
The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord.
Early antiretroviral therapy in HIV-1 infected infants in Europe, 1996-2008: treatment response and
duration of first line regimens.
AIDS 2011,25:2279-2287
Tejiokem, M.C., A. Faye, I.C. Penda, G. Guemkam, F. Ateba Ndongo, G. Chewa, C. Rekacewicz, D.
Rousset, A. Kfutwah, P. Boisier, and J. Warszawski, Feasibility of early infant diagnosis of HIV in
resource-limited settings: the ANRS 12140-PEDIACAM study in Cameroon.
PLoS One, 2011. 6(7):p.e21840.
Simon A, Warszawski J, Kariyawasam D, Le Chenadec J, Benhammou V, Czernichow P, Foissac F,
Laborde K, Treluyer JM, Firtion G, Layouni I, Munzer M, Bavoux F, Polak M, and Blanche S.
Association of prenatal and postnatal exposure to lopinavir-ritonavir and adrenal dysfunction among
uninfected infants of HIV-infected mothers.
Jama. 2011. 306(1):p.70-8.
Kfutwah AK, Tejiokem MC, Ateba FN, Ndongo JA, Penda IC, Ngoupo PA, Tchendjou P, Chewa G,
Boisier P, Rouzioux, C Warszawski J, and Faye A. Seronegativation in Early Treated HIV-Infected
Infants: Frequency and Potential Implications on Care and Follow-up in a Resource-Limited Country.
J Acquir Immune Defic Syndr. 2011.58(2):p.e43-e46
Castro H, Judd A, Gibb DM, Butler K, Lodwick RK, van Sighem A, Ramos JT, Warsawski J, Thorne C,
Noguera-Julian A, Obel N, Costagliola D, Tookey PA, Colin C, Kjaer J, Grarup J, Chene G, and Phillips
A. Risk of triple-class virological failure in children with HIV: a retrospective cohort study.
Lancet. 2011 .377(9777):p.1580-7.
Briand N, Mandelbrot L, Blanche S, Tubiana R, Faye A, Dollfus C, Le Chenadec J, Benhammou V,
Rouzioux C, and J Warszawski, Previous antiretroviral therapy for prevention of mother-to-child
transmission of HIV does not hamper the initial response to PI-based multitherapy during subsequent
pregnancy.
J Acquir Immune Defic Syndr. 2011.57(2):p.126-35.
Frange P, Briand N, Avettand-fenoel V, Veber F, Moshous D, Mahlaoui N, Rouzioux C, Blanche S,
Chaix ML. Lopinavir/ritonavir-based antiretroviral therapy in human immunodeficiency virus type 1infected naive children: rare protease inhibitor resistance mutations but high lamivudine/emtricitabine
resistance at the time of virologic failure.
Pediatr Infect Dis J. 2011 Aug;30(8):684-8
7
2010
Burgard M, Jasseron C, Matheron S, Damond F, Hamrene K, Blanche S, Faye A, Rouzioux C,
Warszawski J, Mandelbrot L; ANRS French Perinatal Cohort EPF-CO1. Mother-to-child transmission of
HIV-2 infection from 1986 to 2007 in the ANRS French Perinatal Cohort EPF-CO1.
Clin Infect Dis. 2010 Oct 1;51(7):833-43.
Dollfus C, Lechenadec J, Faye A, Blanche S, N Briand, Rouzioux C, Warszawski J. Long-term outcomes
of adolescents perinatally infected with HIV-1 and followed since birth in the French Pediatric Cohort
EPF –ANRS C010.
Clin Infect Dis. 2010 Jul 15;51(2):214-24
Tubiana R, Lechenadec J, Rouzioux C, Mandelbrot L, Hamrene K, Dollfus C, Faye A, Delaugerre C,
Blanche S, Warszawski J; for the ANRS French Perinatal Cohort (ANRS CO1/CO11). Factors
associated with HIV-1 mother to child transmission despite a maternal viral Load < 500 copies/ml at
delivery. Case control study nested in the French Perinatal Cohort (EPF- ANRS CO1).
Clin Infect Dis. 2010 ;50(4): 585-96
Frange P, Burgard M, Lachassinne E, le Chenadec J, Chaix ML, Chaplain C, Warszawski J, Dollfus C,
Faye A, Rouzioux C, Blanche S; ANRS French Perinatal Cohort Study Group. Late postnatal HIV
infection in children born to HIV-1-infected mothers in a high-income country.
AIDS. 2010 Jul 17;24(11):1771-6
The PLATO II Project Team for the Collaboration of Observational HIV Epidemiological Research
Europe (COHERE) Group. Triple class virologic failure in HIV-infected patients on antiretroviral
therapy for up to 10 years.
Arch Intern Med. 2010 Mar 8;170(5):410-9.
2009
Delaugerre C, Chaix ML, Blanche S, Warszawski J, Cornet D, Dollfus C, Schneider V, Burgard M, Faye
A, Mandelbrot L, Tubiana R, Rouzioux C; ANRS French Perinatal Cohort. Perinatal acquisition of drugresistant HIV-1 infection: mechanisms and long-term outcome.
Retrovirology. 2009 Sep 19;6:85.
Guibert G, Warszawski J, Le Chenadec J, Blanche S, Benmebarek Y, Mandelbrot L, Tubiana R,
Rouzioux C, Leruez-Ville M; on behalf of the French Perinatal Cohort (EPF). Decreased risk of
congenital cytomegalovirus (CMV) infection in children born to HIV infected mothers in the era of highly
active antiretroviral therapy (HAART).
CID. 2009 Jun 1;48(11):1516-25.
N Briand, L. Mandelbrot, J. Le Chenadec, R. Tubiana, J.P. Teglas, A. Faye, C. Dollfus, C. Rouzioux, S.
Blanche, J. Warszawski; for the ANRS French Perinatal Cohort. No relation between in utero exposure to
highly active antiretroviral therapy and intrauterine growth retardation.
AIDS. 2009 Jun 19;23(10):1235-43.
Goetghebuer T, Haelterman E, Le Chenadec J, Dollfus C, Gibb D, Judd A, Green H, Galli L, Ramos JT,
Giaquinto C, Warszawski J, Levy J; for the European Infant Collaboration group. Effect of early
antiretroviral therapy on the risk of AIDS/death in HIV-infected infants.
AIDS. 2009 23(5):597-604
8
Avettand-Fènoël V, Chaix ML, Blanche S, Burgard M, Floch C, Toure K, Allemon MC, Warszawski J,
Rouzioux C; French Pediatric Cohort Study ANRS-CO 01 Group. LTR real-time PCR for HIV-1 DNA
quantitation in blood cells for early diagnosis in infants born to seropositive mothers treated in HAART
area (ANRS CO 01).
J Med Virol. 2009 Feb;81(2):217-23.
Mandelbrot L, Jasseron C, Ekoukou D, Batallan A, Bongaoin A, Pannier E, Blanche S, Tubiana R,
Rouzioux C, Warszawski J; for the ANRS French Perinatal Cohort (EPF). Amniocentesis and mother-tochild HIV transmission in the ANRS-French Perinatal Cohort.
Am J Obstet Gynecol. 2009 Feb;200 (2):160 e1-9.
2008
Benhammou V, Warszawski J, Bellec S, Doz F, André N, Lacour B, Levine M, Bavoux F, Tubiana R,
Mandelbrot L, Clavel J, Blanche S; on behalf ANRS-Enquête Périnatale Française. Incidence of cancer in
children perinatally exposed to nucleoside reverse transcriptase inhibitors.
AIDS. 2008 Oct 18;22(16):2165-2177.
Jasseron C, Mandelbrot L , Tubiana R, Teglas J.P., Faye A, Dollfus C., Le Chenadec J., Rouzioux C.,
Blanche S., Warszawski J ; ANRS French Perinatal Cohort. Prevention of mother-to-child HIV
transmission: similar access for sub-Sahara African immigrants and for French women?
AIDS. 2008 Jul 31;22(12):1503-11
Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Study Group.
Response to combination antiretroviral therapy: variation by age.
AIDS. 2008 Jul 31;22(12):1463-73.
Warszawski J, Tubiana R, Le Chenadec J, Teglas JP, Faye A, Dollfus C, Briand N, Jasseron C, Rouzioux
C, Blanche S, Mandelbrot L. Transmission mère-enfant du VIH en France : l’impact majeur des
stratégies de prévention – Résultats de l’Enquête périnatale française ANRS-EPF.
BEH Numéro thématique n° 14-15, 2008, 98-101.
Warszawski J, Tubiana R, Le Chenadec J, Blanche S, Teglas JP, Dollfus C, Faye A, Burgard M,
Rouzioux C, Mandelbrot L; ANRS French Perinatal Cohort. Mother-to-child HIV transmission despite
antiretroviral therapy in the ANRS French Perinatal Cohort.
AIDS. 2008 Jan 11;22(2):289-99.
2007
Papaleo A, Warszawski J, Salomon R, Jullien V, Veber F, Dechaux M, Blanche S. Increased beta-2
microglobulinuria in human immunodeficiency virus-1-infected children and adolescents treated with
tenofovir.
Pediatr Infect Dis J. 2007 Oct;26(10):949-51.
Warszawski J, Lechenadec J, Faye A, Dollfus C, Firtion G, Meyer L, Douard D, Monpoux F, Tricoire J,
Benmebarek Y, Rouzioux C, Blanche S. Long-term non progression of HIV-1 infection in children.
Evaluation in the prospective French Pediatric Cohort EPF-ANRS.
Clin Infect Dis. 2007 Sept 15;45(6):785-94
9
Delaugerre C, Warszawski J, Chaix ML, Veber F, Macassa E, Buseyne F, Rouzioux C, Blanche S.
Prevalence and risk factors associated with antiretroviral resistance in HIV.
J Med Virol. 2007 Sept;79(9):1261-9.
Newell ML, Huang S, Fiore S, Thorne C, Mandelbrot L, Sullivan JL, Maupin R, Delke I, Watts DH,
Gelber RD, Cunningham CK; PACTG 316 Study Team. Characteristics and management of HIV-1infected pregnant women enrolled in a randomised trial: differences between Europe and the USA.
BMC Infect Dis. 2007 Jun 20;7:60.
Scavalli Palladino C, Mandelbrot L, Berrebi A, Batallan A, Cravello L, Pannier E, Hamrene K, CiraruVigneron N, Faye A, Warszawski J, ANRS EPF. Twin pregnancy as a risk factor for mother-to-child
transmission of HIV-1 : trends over 20 years.
AIDS. 2007 May 11;21(8):993-1002.
Benhammou V, Tardieu M, Warszawski J, Rustin P, Blanche S. Clinical mitochondrial dysfunction in
uninfected children born to HIV-infected mothers following perinatal exposure to nucleoside analogues.
Environ Mol Mutager. 2007 Apr-May ;48(3-4) :173-8
Delaugerre C, Chaix ML, Warszawski J, Rouzioux C, Blanche S. HIV-1 drug resistance in French
infected-children: from newborn to adolescent.
Arch Pediatr. 2007 Mar;14(3):298-302.
Blanche S. Possible long-term effect of in utero antiretroviral exposure?
Arch Pediatr. 2007, 14(6):610-1
2006
S Blanche, M Tardieu, V Benhammou, J Warszawski and P Rustin. Mitochondrial dysfunction following
perinatal exposure to nucleoside analogues.
AIDS 2006, 20:1685-1690.
Articles dans des revues nationales avec comité de lecture
Warszawski J, Tubiana R, Le Chenadec J, Teglas JP, Faye A, Dollfus C, Briand N, Jasseron C, Rouzioux
C, Blanche S, Mandelbrot L. Transmission mère-enfant du VIH en France : l’impact majeur des
stratégies de prévention – Résultats de l’Enquête périnatale française ANRS-EPF.
BEH Numéro thématique n° 14-15, 2008, 98-101.
Delaugerre C, Chaix ML, Warszawski J, Rouzioux C, Blanche S. [HIV-1 drug resistance in French
infected-children: from newborn to adolescent ]
Arch Pediatr. 2007 Mar;14 : 298-302.
Warszawski J, Goulet V. Chlamydia trachomatis : études de prévalence dans des structures de médecine
à vocation préventive.
BEH Numéro thématique 2006, 37-38.
Livres ou chapitres de livres
Jasseron C, Warszawski J. L’accès à la prévention de la transmission mère-enfant du VIH en France. In :
De La Rochebrochard, E. De la Pilule au bébé éprouvette. Choix individuels ou stratégie médicale
INED 2008
10
Posters, communications orales dans des conférences nationales et internationales
Briand N, Viard JP, Dollfus C, Boufassa F, Le Chenadec J, Goujard J, Seng R, Blanche S, Meyer L,
Warszawski J, and ANRS EPF, COVERTE, PRIMO, SEROCO, COPANA study-groups. Current HIV-1
Viral Load Is Less Often Undetectable in Young Adults Infected Perinatally Than in Older Patients
Infected During Adulthood, in France.
20ème Conference on Retroviruses and Opportunistic Infections. Atlanta, GA. 3-6 Mars 2013-Young
Investigator Award
Briand N, Warszawski J, Faye A, Le Chenadec J, Dollfus C, Teglas JP, Tubiana R, Rouzioux C,
Mandelbrot L, Blanche S, ANRS EPF study group. Is Intrapartum Prophylaxis for Mother-to-Child HIV1 Transmission Still Useful in the HAART Era?
20ème Conference on Retroviruses and Opportunistic Infections. Atlanta, GA. 3-6 Mars 2013-Young
Investigator Award
Sibiude J, Mandelbrot L, Blanche S, Le Chenadec J, Bouallag N, Faye A, Dollfus C, Tubiana R,
Khoshnood B, Warszawski J; for the ANRS French Perinatal Cohort. Birth Defects and Antiretroviral
Therapy in the EPF French Perinatal Cohort, a prospective exhaustive study among 13,124 live births
from 1994 to 2010.
Communication orale, 20ème Conference on Retroviruses and Opportunistic Infections. Atlanta, GA. 3-6
Mars 2013
Blanche S, Scott-Algara D, Le Chenadec J, Avettand-Fenoel V, Bouallag N, Rouzioux C, Viard J-P,
Dollfus C, Warsawski J, Buseyne F. Preservation of Naive CD4 and CD8 T Lymphocytes 15 Years or
More after Perinatal HIV Infection - The ANRS-EP38-IMMIP study.
20ème Conference on Retroviruses and Opportunistic Infections. Atlanta, GA. 3-6 Mars 2013
Briand N, Viard JP, Le Chenadec J, Dollfus C, Firtion G, Arvieux C, Funck-Brentano I, Reliquet V,
Jeantils V, Boufassa L, Chrétien F, Ferey C, Ramos E, Blanche S, Meyer L, Warszawski J, ANRS CO19
Coverte group. Clinicians Underestimate Sexual Risk Behaviour in Female Patients with Perinatally
Acquired Human Immunodeficiency Virus Infection. ANRS CO19 COVERTE cohort. 4th International
Workshop on HIV Pediatrics.
Washington, DC, Etats-Unis. 20-21 Juillet 2012
Briand N, Viard JP, Le Chenadec J, Dollfus C, Firtion G, Arvieux C, Funck-Brentano I, Reliquet V,
Jeantils V, Boufassa L, Chrétien F, Ferey C, Ramos E, Blanche S, Meyer L, Warszawski J, ANRS CO19
Coverte group. Clinicians Underestimate Sexual Risk Behaviour in Female Patients with Perinatally
Acquired Human Immunodeficiency Virus Infection. ANRS CO19 COVERTE cohort.
19e Congrès International sur le Sida. Washington, DC, Etats-Unis. 22-27 Juillet 2012
J Warszawski, J Le Chenadec, L Mandelbrot, A Faye, C Dollfus, Z Assoul, R Tubiana,,S Blanche, and
The French Perinatal Cohort (ANRS CO1/CO11). Infant Mortality Among HIV-Uninfected Children
During the HAART Era in France – The ANRS French Perinatal Cohort.
19th CROI, Seattle 2012
Aupiais C, Faye A, Le Chenadec J, Dollfus C, Rouzioux C, Bouallag N, Laurent C, Blanche S,
Warszawski J, ANRS EPF French Pediatric Cohort. Unplanned interruption of cART in HIV1-infected
children: frequency, context, and subsequent immunological outcomes in the ANRS French Pediatric
Cohort.
19th CROI, Seattle 2012 -Young Investigator Award
11
A. Rachas, J. Warszawski, J. Le Chenadec, C. Legeai, J.P. Teglas, C. Goujard, C. Rouzioux, L.
Mandelbrot, R. Tubiana, L. Meyer. One Third of Women Beginning cART During Pregnancy Do Not
Reach Undetectable (<50 copies/mL) Viral Load at Delivery: Does Pregnancy Affect Response to cART?
19th CROI, Seattle 2012 - Young Investigator Award
J Sibiude, J Warszawski, R Tubiana, C Dollfus, A Faye, C Rouzioux, J Teglas, D Ekoukou, S Blanche, L
Mandelbrot, and the ANRS French Perinatal Cohort (ANRS CO1/CO11). Large Increase in Prematurity
between 1990 and 2009 in HIV-Infected Women in the National ANRS French Perinatal Cohort: does
Ritonavir Boost Play a Role?
18th CROI, San Francisco 2011, Young Investigator Award pour communication orale + poster
Jérôme Le Chenadec, Stéphane Blanche, Véronique Avettand-Fenoel, Naima Bouallag, Christine
Rouzioux, Jean-Paul Viard, Catherine Dollfus, Daniel Scott-Algara, Josiane Warszawski, and Florence
Buseyne. Infrequent Gag-specific CD4 and CD8 T Cell Proliferation Capacity following 15 Years of
Perinatal HIV Infection - The ANRS-EP38-IMMIP Study.
18th CROI, San Francisco 2011
R Tubiana, S Matheron, J Le Chenadec, C Dollfus, A Faye, S Blanche, C Rouzioux, V Benhammou, L
Mandelbrot, J Warszawski. Extremely Low Risk of Mother-To-Child Transmission of HIV in Women
Starting HAART before Pregnancy in the French Perinatal Cohort (ANRS EPF CO1/11).
18th CROI, San Francisco 2011
V. Avettand-Fenoel, S. Blanche, J. Lechenadec, C. Dollfus, D. Scott-Algara4 J.-P. Viard, N. Bouallag, Y.
Benmebarek, Y. Rivière, J. Warszawski, C. Rouzioux, F. Buseyne. The cell-associated HIV-1 DNA level
after 15 years of perinatal infection is strongly correlated with lifetime viral replication - The ANRSEP38-IMMIP Study.
AIDS 2010 International Conference, Vienna, July 2010 , communication orale
Warszawski J, Faye A, Ecochard E, Dollfus C, Tubiana R, Rouzioux C, Mandebrot L, Blanche S; For the
ANRS CO1-EPF. Effects of intensified prophylaxis during the post-natal phase on mother-to-child
transmission of HIV-1. The ANRS CO1- French Perinatal Cohort EPF.
AIDS 2010 International Conference, Vienna, July 2010
Tejiokem M., J. Warszawski, A Kfutwah, F. Ateba, C. Same Ekobo, I. Penda, G. Guemkam, JA Ndongo,
G. Chewa, D. Rousset, P Boisier, A Faye. The impact of different antiretroviral regimens on prevention
of HIV mother to child transmission in routine practice in Cameroon (ANRS 12140-PEDIACAM)”.
abstract number: MOPE0271.
18th AIDS 2010 International Conference, Vienna, July 2010
Tejiokem M, Warszawski J, Kfutwah A, Francis A, Same Ekobo C, Penda I, Guemkam G, Boisier P,
Rousset D, Faye A. Faisabilité des multithérapies anti-rétrovirales précoces systématiques chez les
nourrissons âgés de moins de 7 mois infectés par le VIH dans un pays à ressources limitées : ANRS
12140 – PEDIACAM.
5ème Conférence Francophone VIH/SIDA, Casablanca 2010
F Buseyne, V Avettand-Fenoel, J Lechenadec, C Dollfus, D Scott, JP Viard, N Bouallag, Y Benmebarek,
Y Rivière, J Warszawski, C Rouzioux, S Blanche. Histoire de l’infection périnatale par le VIH, 15
ans après la contamination périnatale: quantité d’ADN-VIH et nombre de lymphocytes T CD4 -Etude
ANRS-EP38-IMMIP.
Colloque ANRS, Institut Pasteur
Beltzer N, Bigot R, Beck F, Toulemon L, David C, Gremy I, Warszawski J. Vers une nouvelle
méthodologie des enquêtes en santé réalisées à partir d’abonnés au téléphone.
Colloque francophone sur les sondages. Tanger 2010.
12
Frange P, Burgard M, Lachassinne E, Warszawski J, Dollfus C, Le Chenadec J, Benhammou V, Guillot
F, Rouzioux C, Blanche S. Infection postnatale tardive à VIH-1 en France en l’absence d’allaitement
maternel : l’expérience de la cohorte périnatale ANRS CO01.
5ème Conférence Francophone VIH/SIDA, Casablanca 2010
Briand N, Mandelbrot L, Blanche S, Tubiana R, Faye A, Dollfus C, Le Chenadec J, Benhammou V,
Rouzioux C, Warszawski J ; for the ANRS French Perinatal Cohort (ANRS EPF-CO1) Response to PIbased HAART in pregnant women previously exposed to ART for PMTCT.
17th CROI, San Francisco 2010
C Jasseron, L Mandelbrot, C Dolfus, N Trocmé, R Tubiana, JP Teglas, A Faye, C Rouzioux, S Blanche,
Warszawski J; for the ANRS French Perinatal Cohort EPF - Non-disclosure of maternal HIV status to the
father during pregnancy : risk factors and consequences.
17th CROI, San Francisco 2010
Tubiana R, Rouzioux C, Lechenadec J, Hamrene K, Mandelbrot L, Dollfus C, Faye A, Blanche S,
Delaugerre C, Warszawski J; and ANRS French Perinatal Cohort Study Group. Delayed Control of
Maternal Viral Load during Pregnancy Is Associated with Higher Risk of MTCT despite Viral Loads of
<500 Copies/mL at Delivery: A Case/Control Study in the ANRS French Perinatal Cohort CO1/10/11.
16th CROI, Montreal 2009
Jasseron C, Mandelbrot L, Blanche S, Tubiana R, Le Chenadec J, Teglas JP, Dolfus C, Faye A, Rouzioux
C, Warszawski J. Is marital status and information of the father associated with access to prevention of
mother-to-child HIV transmission?
5th International Dominique DORMONT Conference, Paris 2009
Tejiokem M, Guemkam G, Same Ekobo C, Penda I, Nga A, Mbida P, Belinga ML, Tocko C, Ateba
Ndongo F, Ndongo JA, Mekoudjou M, Kfutwah A, Rousset D, Warszawski J, Faye A. Why do HIV
negative mothers refuse to participate in a clinical research involving HIV positive mothers in Cameroon?
5th International Dominique DORMONT Conference, Paris 2009
Kfutwah A, Tejiokem M, Faye A, Yonga M, Warszawski J, Blanche S, Rekacewicz C, Ateba F, Ndongo
J, Guemkam G, Same-Ekobo C, Rouzioux C, Leruez-Ville M, Boisier P. Rousset D. Perinatal
transmission of Cytomegalovirus (CMV) in children born to HIV positive and negative women in
Cameroon.
5th International Dominique DORMONT Conference, Paris 2009
Briand N, Le Chenadec J, Blanche S, Teglas JP, Dollfus C, Faye A, C Rouzioux, Tubiana R, Warszawski
J, Mandelbrot L ; for the ANRS French Perinatal Cohort. Lack of association between birthweight and
prepartum exposition to highly active antiretroviral therapy in HIV-uninfected neonates born to HIVinfected mothers. Poster discussion.
XVII International AIDS Conference Mexico City, 3-8 August 2008
Mandelbrot L, Jasseron C, Ekoukou D, Batallan A, Bongain A, Pannier E, Blanche S, Tubiana R,
Rouzioux C, Warszawski J ; The ANRS French Perinatal Cohort EPF. Amniocentesis and Mother-toChild HIV Transmission: The French ANRS EPF Cohort CO1/11.
15th CROI 2007, Boston 2008.
Desquilbet L, Hoen B, Goujard C, Deveau C, Warszawski J, Meyer L ; and the ANRS PRIMO Cohort
study group. Early Short-course HAART Initiated at the Time of Primary HIV Infection Provides No
Sustained Benefit in Terms of Time to CD4 Decline below 350/mm3: Results of a Propensity Analysis
within the ANRS PRIMO Cohort.
15th CROI 2007, Boston 2008.
13
Guibert G, Warszawski J, Le Chenadec J, Benmebarek Y, Teglas J P, Blanche S, Mandelbrot L, Tubiana
R, Rouzioux C, Leruez-Ville M, and The ANRS French Perinatal Cohort EPF. Congenital
Cytomegalovirus Infection in Infants Born to HIV-infected Mothers, Prevalence and Risk Factors: ANRS
French Perinatal EPF Cohort CO1/10/11.
15th CROI 2007, Boston 2008.
Jasseron C, Burgard M, Teglas J P, Matheron S, Damond F, Hamrene K, Blanche S, Rouzioux C,
Warszawski J, Mandelbrot L, and The ANRS French Perinatal Cohort EPF. Mother-to-Child
Transmission of HIV-2: The French ANRS Perinatal Cohort EPF-CO1/11.
15th CROI 2007, Boston 2008.
Delaugerre C, Cornet D, Chaix ML, Warszawski J, Dollfus C, Burgard M, Faye A, Mandelbrot L,
Tubiana R, Blanche S, Rouzioux C. Analyse moléculaire des mécanismes d’acquisition de virus résistants
lors de la primo-infection du nouveau-né exposé. Communication orale.
4ème conférence francophone VIH/Sida Paris 2007 aux antirétroviraux
Mandelbrot L, Palladino C, Berrebi A, Rouzioux C, Teglas JP, Blanche S, Faye A, Tubiana R,
Warszawski J, (ANRS) Co1 Enquête Périnatale Française (EPF). Particularités de la transmission mèreenfant du VIH-1 dans les grossesses gémellaires.
4ème conférence francophone VIH/Sida Paris 2007
Jasseron C, Mandelbrot L, Teglas JP, Tubiana R, Le Chenadec J, Rouzioux C, Blanche S, Warszawski J,
ANRS-EPF. Enquête Périnatale Française. Accès à la prévention de la transmission mère-enfant du
VIH selon l’origine géographique des femmes enceintes en France.
4ème conférence francophone VIH/Sida Paris 2007
Warszawski J, Tubiana R, Le Chenadec J, Blanche S, Teglas JP, Dollfus C, Faye A, Burgard M,
Rouzioux C, Mandelbrot L ; ANRS-EPF. Enquête Périnatale Française2 . Transmission mère-enfant du
VIH à l’ère des multithérapies dans l’Enquête Périnatale Française (ANRS-EPF). Communication orale.
4ème conférence francophone VIH/Sida Paris 2007
Jasseron C, Warszawski J, Blanche S, Rouzioux C, Le Chenadec J, Dolfus C, Faye A, Hamrene K, Teglas
J.P, Tubiana R, Mandelbrot L, ANRS French Perinatal Cohort (EPF). Prevention of mother-to-child HIV
transmission in France : is access to care different for women from sub-Saharan Africa than for French
women ? Communication orale.
4ème conférence internationale Dominique Dormont, Paris 2007.
Avettand-Fenoel V, Chaix ML, Blanche S, Burgard M, Warszawski J, Rouzioux C. Early diagnosis of
HIV-1 infection in newborns, in the context of prevention of mother-to-child transmission with HAART
(Perinatal Cohort ANRS Co 01). Communication orale.
4ème conférence internationale Dominique Dormont, Paris 2007.
Goetghebuer T, Haelterman E, Hainaut M, Warszawski J, Le Chenadec J, Dollfus C, Gibb D.M,
Giaquinto C, Levy J. for the European Infant Collaboration Group. Early versus deferred highly active
antiretroviral therapy in HIV infected infants : a European collaborative cohort study. Communication
orale.
4ème conférence internationale Dominique Dormont, Paris 2007.
Guibert G, Leruez-Ville M, Rouzioux C, Tubiana R, Mandelbrot L, Blanche S, Teglas JP, BenMebarek
Y, Le Chenadec J, Warszawski J, ANRS French Perinatal Cohort (EPF). High prevalence of
cytomegalovirus (CMV) infection in infants born to HIV infected mothers–ANRS French Perinatal
Cohort (EPF). Communication orale.
4ème conférence internationale Dominique Dormont, Paris 2007.
14
Warszawski J, J lechenadec, C Dollfus, C Rouzioux, J Teglas, A Faye, S Blanche, and ANRS-EPF study
group. Long term non progression : Children too ! Prospective evaluation in the ANRS French Pediatric
Cohort.
14th CROI 2007, Los Angeles 2007
C Dollfus, J Le Chenadec, A Faye, S Blanche, C Rouzioux, J Tricoire, G Firtion, E Lachassinne, J
Warszawski, and the French Pediatric Cohort EPF. Long-term Clinical and Biological Outcomes in
Children Vertically Infected with HIV.
13th CROI 2006, Denver 2006
C. Delaugerre, D Cornet, M L Chaix, J Warszawski, C Dollfus, M Burgard, L Mandelbrot, R Tubiana, S
Blanche, and C Rouzioux. Mechanisms of Acquisition of ART Drug-resistant Virus in HIV-1-infected
Newborns in the French Perinatal Cohort (EPF-ANRS).
13th CROI 2006, Denver 2006
15
16
Abstracts
17
AIDS. 2013 Jan 28;27(3):357-67.
Does pregnancy affect the early response to cART?
Rachas A, Warszawski J, Le Chenadec J, Legeai C, Teglas JP, Goujard C, Rouzioux
C, Mandelbrot L, Tubiana R, Meyer L.
OBJECTIVE
A part of women starting antiretroviral therapy during pregnancy fail to attain undetectable viral
load by delivery. Here we studied whether pregnancy affects the early immunovirological
response to combined antiretroviral therapy (cART), taking into account treatment duration and
baseline characteristics.
DESIGN
Antiretroviral-naive women initiating cART since 2004 and followed in three French ANRS
multicenter HIV cohorts (French Perinatal Cohort, PRIMO and COPANA).
METHODS
The early virological response (at 1, 3 and 6 months) and immunological increase after cART
initiation were compared between women starting cART during (n = 708) and outside (n = 110)
pregnancy. Relative risks were estimated in multivariate models adjusted for treatment duration,
baseline viral load and CD4, sociodemographic factors and chronic hepatitis B. CD4 increases
were compared by using mixed models.
RESULTS
Only 63.8% of treated pregnant women attained a viral load less than 50 copies/ml by delivery.
Similarly to nonpregnant women, nearly 90% of pregnant women reached a viral load less than
400 copies/ml at M3 [adjusted RR: 1.0 (95% confidence interval 0.7-1.4)], and nearly 100% at
M6 following cART initiation [0.9 (0.4-1.9)]. viral load less than 50 copies/ml was attained by
61.5% of pregnant versus 67.9% of nonpregnant women at M3 (P = 0.26), and by 82.1 versus
87.0% at M6 (P = 0.48). CD4 recovery (both number and percentage) was similar in pregnant
and nonpregnant women. Results were similar for the subset of women starting a boosted
protease inhibitor-containing cART.
CONCLUSION
Pregnancy does not affect the virological response to cART below 400 copies/ml, or CD4
increase. The main reason for pregnant women not achieving viral load less than 50 copies/ml
at delivery appears to be a short duration of treatment.
18
AIDS Behav. 2013 Feb;17(2):488-97.
Non-disclosure of a pregnant woman's HIV status to her partner is
associated with non-optimal prevention of mother-to-child transmission.
Jasseron C, Mandelbrot L, Dollfus C, Trocmé N, Tubiana R, Teglas JP, Faye A, Rouzioux
C, Blanche S, Warszawski J.
Our objective was to study relations between non-disclosure of HIV to partner, socio
demographics and prevention of HIV mother-to-child transmission (PMTCT), among HIVinfected pregnant women enrolled in the French Perinatal Cohort (ANRS-EPF-CO1) from 2005
to 2009 (N = 2,952). Fifteen percent of the women did not disclose their HIV status to their
partner. Non-disclosure was more frequent in women diagnosed with HIV infection late in
pregnancy, originating from Sub-Saharan Africa or living alone, as well as when the partner was
not tested for HIV. Non-disclosure was independently associated with non optimal PMTCT: late
initiation of antiretroviral therapy, detectable viral load at delivery and lack of neonatal
prophylaxis. Nonetheless, the rate of transmission did not differ according to disclosure status.
Factors associated with non-disclosure reflect vulnerability and its association with non optimal
PMTCT is a cause for concern although the impact on transmission was limited in this context
of universal free access to care.
19
J Infect Dis. 2013 Mar;207(5):759-67.
Predictors of CD4+ T-Cell Counts of HIV Type 1–Infected Persons After
Virologic Failure of All 3 Original Antiretroviral Drug Classes
Pursuing Later Treatment Option II (PLATO II) Project Team of the Collaboration of
Observational HIV Epidemiological Research Europe (COHERE).
Background
Low CD4 + T-cell counts are the main factor leading to clinical progression in human
immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting
CD4+ T-cell counts after triple-class virological failure.
Methods
We included individuals from the COHERE database who started antiretroviral therapy from
1998 onward and who experienced triple-class virological failure. CD4 + T-cell counts obtained
after triple-class virologic failure were analyzed using generalized estimating equations.
Results
The analyses included 2424 individuals with a total of 23 922 CD4 + T-cell count
measurements. In adjusted models (excluding current viral load and year), CD4+ T-cell counts
were higher with regimens that included boosted protease inhibitors (increase, 22 cells/µL [95%
confidence interval {CI}, 3.9–41]; P = .017) or drugs from the new classes (increase, 39 cells/µL
[95% CI, 15–62]; P = .001), compared with nonnucleoside reverse-transcriptase inhibitor–based
regimens. These associations disappeared when current viral load and/or calendar year were
included. Compared with viral levels of <2.5 log10 copies/mL, levels of 2.5–3.5, 3.5–4.5, 4.5–5.5,
and >5.5 log10 copies/mL were associated with CD4+ T-cell count decreases of 51, 84, 137, and
186 cells/µL, respectively (P < .001).
Conclusions
The approximately linear inverse relationship between log 10 viral load and CD4+ T-cell count
indicates that there are likely immunologic benefits from lowering viral load even by modest
amounts that do not lead to undetectable viral loads. This is important for patients with low
CD4+ T-cell counts and few drug options.
20
BMC Infect Dis. 2012 Oct 10;12:251. doi: 10.1186/1471-2334-12-251.
A three-source capture-recapture estimate of the number of new HIV
diagnoses in children in France from 2003-2006 with multiple imputation of a
variable of heterogeneous catchability.
Héraud-Bousquet V, Lot F, Esvan M, Cazein F, Laurent C, Warszawski J, Gallay A.
BACKGROUND
Nearly all HIV infections in children worldwide are acquired through mother-to-child
transmission (MTCT) during pregnancy, labour, delivery or breastfeeding. The objective of our
study was to estimate the number and rate of new HIV diagnoses in children less than 13 years
of age in mainland France from 2003-2006.
METHODS
We performed a capture-recapture analysis based on three sources of information: the
mandatory HIV case reporting (DOVIH), the French Perinatal Cohort (ANRS-EPF) and a
laboratory-based surveillance of HIV (LaboVIH). The missing values of a variable of
heterogeneous catchability were estimated through multiple imputation. Log-linear modelling
provided estimates of the number of new HIV infections in children, taking into account
dependencies between sources and variables of heterogeneous catchability.
RESULTS
The three sources observed 216 new HIV diagnoses after record-linkage. The number of new
HIV diagnoses in children was estimated at 387 (95%CI [271-503]) from 2003-2006, among
whom 60% were born abroad. The estimated rate of new HIV diagnoses in children in mainland
France was 9.1 per million in 2006 and was 38 times higher in children born abroad than in
those born in France. The estimated completeness of the three sources combined was 55.8%
(95% CI [42.9 - 79.7]) and varied according to the source; the completeness of DOVIH (28.4%)
and ANRS-EPF (26.1%) were lower than that of LaboVIH (33.3%).
CONCLUSION
Our study provided, for the first time, an estimated annual rate of new HIV diagnoses in children
under 13 years old in mainland France. A more systematic HIV screening of pregnant women
that is repeated during pregnancy among women likely to engage in risky behaviour is needed
to optimise the prevention of MTCT. HIV screening for children who migrate from countries with
high HIV prevalence to France could be recommended to facilitate early diagnosis and
treatment.
21
J Virol. 2012 Oct;86(19):10540-6
The breadth and titer of maternal HIV-1-specific heterologous neutralizing
antibodies are not associated with a lower rate of mother-to-child
transmission of HIV-1.
Chaillon A, Wack T, Braibant M, Mandelbrot L, Blanche S, Warszawski J, Barin F.
It has been hypothesized that neutralizing antibodies (NAbs) should have broad specificity to be
effective in protection against diverse HIV-1 variants. The mother-to-child transmission model of
HIV-1 provides the opportunity to examine whether the breadth of maternal NAbs is associated
with protection of infants from infection. Samples were obtained at delivery from 57 transmitting
mothers (T) matched with 57 nontransmitting mothers (NT) enrolled in the multicenter French
perinatal cohort (ANRS EPF CO1) between 1990 and 1996. Sixty-eight (59.6%) and 46 (40.4%)
women were infected by B and non-B viruses, respectively. Neutralization assays were carried
out with TZM-bl cells, using a panel of 10 primary isolates of 6 clades (A, B, C, F, CRF01_AE,
and CRF02_AG), selected for their moderate or low sensitivity to neutralization. Neutralization
breadths were not statistically different between T and NT mothers. However, a few statistically
significant differences were observed, with higher frequencies or titers of NAbs toward several
individual strains for NT mothers when the clade B-infected or non-clade B-infected mothers
were analyzed separately. Our study confirms that the breadth of maternal NAbs is not
associated with protection of infants from infection.
22
Clin Infect Dis. 2012 May;54(9):1348-60
Premature delivery in HIV-infected women starting protease inhibitor
therapy during pregnancy: role of the ritonavir boost?
Sibiude J, Warszawski J, Tubiana R, Dollfus C, Faye A, Rouzioux C, Teglas JP, Ekoukou
D, Blanche S, Mandelbrot L.
BACKGROUND
The association between combination antiretroviral (cARV) therapy use by human
immunodeficiency virus (HIV)-infected women during pregnancy and risk of prematurity is still
controversial. We explored this question, focusing on the initiation of ritonavir-boosted protease
inhibitors (PIs) during pregnancy, which is now standard care.
METHODS
Trends in prematurity (<37 gestational weeks) were studied among all singleton pregnancies in
the Agence Nationale de Recherche sur le SIDA (ANRS) French Perinatal Cohort from 1990
through 2009 (n = 13 271). In-depth analysis was conducted in a more detailed substudy of the
cohort, among women starting PI-based ARV therapy during pregnancy (n = 1253).
Multivariable analysis adjusted for immunovirological status and known risk factors for
prematurity.
RESULTS
Prematurity increased from 9.2% during 1990-1993 (no therapy) and 9.6% during 1994-1996
(mostly zidovudine monotherapy) to 12.4% during 1997-1999 (dual-nucleoside analog therapy)
and 14.3% during 2005-2009 (routine cARV therapy; P < .01). Prematurity was associated with
cARV therapy, compared with zidovudine monotherapy, with an adjusted odds ratio of 1.69
(95% confidence interval [CI], 1.38-2.07; P < .01) when accounting for maternal age,
intravenous drug use, geographic origin, and CD4 cell count. During 2005-2009, the prematurity
rate was higher with boosted than with nonboosted PI therapy started during pregnancy (14.4%
vs 9.1% [P = .05]; adjusted hazard ratio, 2.03 [95% CI, 1.06-3.89; P = .03] in multivariate
analysis). The difference concerned mainly induced preterm delivery for maternal or fetal
indications (5.6% vs 1.6%; P = .02),
CONCLUSIONS
The prematurity rate among HIV-infected pregnant women was twice that in the general
population in France; this was not entirely explained by sociodemographic characteristics.
Prematurity was independently associated with cARV therapy and, particularly, with the
initiation of ritonavir-boosted PI therapy during pregnancy.
23
Clin Infect Dis. 2012 Mar;54(6):878-81
Short- and long-term immunological and virological outcome in HIV-infected
infants according to the age at antiretroviral treatment initiation.
Goetghebuer T, Le Chenadec J, Haelterman E, Galli L, Dollfus C, Thorne C, Judd
A, Keiser O, Ramos JT, Levy J, Warszawski J;European Infant Collaboration Group.
The clinical benefit of antiretroviral therapy in infants is established. In this cohort collaboration,
we compare immunological and virological response to treatment started before or after 3
months of age. Early initiation provides a better short-term response, although evolution after 12
months of age is similar in both groups.
24
J Infect Dis. 2012 May 15;205(10):1520-8
Relationships between HIV disease history and blood HIV-1 DNA load in
perinatally infected adolescents and young adults: the ANRS-EP38-IMMIP
study.
Avettand-Fenoel V, Blanche S, Le Chenadec J, Scott-Algara D, Dollfus C, Viard
JP, Bouallag N, Benmebarek Y, Rivière Y, Warszawski J, Rouzioux C, Buseyne F.
BACKGROUND
Our aim was to study the impact of lifelong human immunodeficiency virus (HIV) disease history
on the current immune and virological status of perinatally infected patients reaching adulthood.
We evaluated blood cell-associated HIV DNA load as an indicator of cell-associated HIV
reservoirs and an independent predictor of disease progression.
METHODS
The ANRS-EP38-IMMIP Study included 93 patients aged 15-24 years who were infected with
HIV during the perinatal period. HIV DNA load was quantified by real-time polymerase chain
reaction.
RESULTS
Eighty-five percent of patients were receiving highly active antiretroviral therapy (HAART), and
HIV RNA was undetectable in the plasma of 75% of these patients. The median HIV DNA load
was 2.84 (interquartile range, 2.51-3.16) log(10) copies per 10(6) peripheral blood mononuclear
cells. In patients with viral suppression, HIV DNA load was independently associated with
cumulative HIV RNA viremia over the last 5 years. HIV DNA load was negatively correlated with
CD4 cell count in patients with active replication but not in those with undetectable HIV RNA.
CONCLUSIONS
In perinatally infected youths who are successfully treated, sustained viral suppression is
associated with a low HIV DNA load. The absence of association between current HIV DNA
load and CD4 cell counts suggests that the unique physiological characteristics of pediatric
infection persist after adolescence.
25
J Pediatr. 2012 Jan;160(1):60-6
Performance of HIV-1 DNA or HIV-1 RNA tests for early diagnosis of
perinatal HIV-1 infection during anti-retroviral prophylaxis.
Burgard M, Blanche S, Jasseron C, Descamps P, Allemon MC, Ciraru-Vigneron N, Floch
C, Heller-Roussin B, Lachassinne E, Mazy F,Warszawski J, Rouzioux C; Agence
Nationale de Recherche sur le SIDA et les Hepatites virales French Perinatal Cohort.
OBJECTIVE
To compare performance of testing for human immunodeficiency virus (HIV)-1 DNA and HIV-1
RNA for diagnosis of HIV-1 infection in infants receiving preventive antiretroviral therapy.
STUDY DESIGN
This substudy of the French multicenter prospective cohort of neonates born to HIV-infected
mothers, included 1567 infants tested for HIV with polymerase chain reaction (PCR) in a single
laboratory, receiving post-natal prophylaxis, not breastfed, and having simultaneous HIV-1 DNA
and RNA results before 45 days. The performance of PCR was assessed in reference to the 6month HIV-1 RNA result.
RESULTS
Specificity of both HIV-1 RNA and HIV-1 DNA PCR was 100% at all ages (except 99.8% for
DNA at birth); sensitivity was 58% (RNA) and 55% (DNA) at birth, and 89% at 1 month, 100% at
3 months for both, and 100% at 6 months (DNA). Concordance between HIV-1 DNA and RNA
results was 0.78 and 0.81 (Kappa) at birth and 1 month and 100% at 3 and 6 months. Type of
maternal and neonatal prophylaxis had no effect on sensitivity, but influenced viral load.
CONCLUSION
The performances of testing for HIV-1 DNA and RNA were similar with 100% sensitivity at 3
months. At 1 month during prophylaxis, 11% of infected children had negative PCR results.
26
AIDS. 2011 Nov 28;25(18):2279-87. doi: 10.1097/QAD.0b013e32834d614c.
Early antiretroviral therapy in HIV-1-infected infants, 1996-2008: treatment
response and duration of first-line regimens.
Judd A; European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study
group in EuroCoord.
OBJECTIVE
To investigate virological and immunological response to antiretroviral therapy (ART), and
predictors of switching and interrupting treatment among infants starting ART across Europe.
DESIGN
Cohort study.
METHODS
Nine cohorts from 13 European countries contributed data on HIV-infected infants born 19962008 and starting ART before age 12 months. Logistic and linear regression, and competing
risks methods were used to assess predictors of virological (viral load <400 copies/ml) and
immunological (change in CD4 Z-score) response, switching to second-line ART and treatment
interruptions with viral load less than 400 copies/ml.
RESULTS
A total of 437 infants were followed for median 5.9 (interquartile range 2.3-7.6) years after
starting ART; 30% had an AIDS diagnosis prior to ART initiation. 53% had suppressed viral load
<400 copies/ml at 12 months in 1996-1999, increasing to 77% in 2004-2008. Virological and
immunological responses at 12 months varied by initial ART type (P < 0.001 and P = 0.03,
respectively), with four-drug nonnucleoside reverse transcriptase inhibitor (NNRTI)-based
regimens being superior [virological response <400 copies/ml adjusted odds ratio = 3.00, 95%
confidence interval (CI) 1.24-7.23; mean increase in CD4 Z-score coefficient = 0.64, 95% CI
0.10-1.17] to both three-drug NNRTI-based (reference) and boosted protease inhibitor regimens
which were similar. Rates of switching to second-line ART were lower among children starting
four-drug NNRTI-based and boosted protease inhibitor-based regimens compared with threedrug NNRTI regimens (P = 0.03). Sixty five percent of infants remained on first-line ART without
treatment interruption after 5 years.
CONCLUSION
Effective and prolonged responses to first-line ART can now be achieved in infants starting
early ART outside trial settings. Superior responses to four-drug NNRTI compared with boosted
protease inhibitor or three-drug NNRTI regimens need further evaluation, as does treatment
interruption following early ART.
27
PLoS One. 2011;6(7):e21840
Feasibility of early infant diagnosis of HIV in resource-limited settings: the
ANRS 12140-PEDIACAM study in Cameroon.
Tejiokem MC, Faye A, Penda IC, Guemkam G, Ateba Ndongo F, Chewa G, Rekacewicz
C, Rousset D, Kfutwah A, Boisier P,Warszawski J; ARNS 12140-PEDIACAM study group.
BACKGROUND
Early infant diagnosis (EID) of HIV is a key-point for the implementation of early HAART,
associated with lower mortality in HIV-infected infants. We evaluated the EID process of HIV
according to national recommendations, in urban areas of Cameroon.
METHODS/FINDINGS
The ANRS12140-PEDIACAM study is a multisite cohort in which infants born to HIV-infected
mothers were included before the 8(th) day of life and followed. Collection of samples for HIV
DNA/RNA-PCR was planned at 6 weeks together with routine vaccination. The HIV test result
was expected to be available at 10 weeks. A positive or indeterminate test result was confirmed
by a second test on a different sample. Systematic HAART was offered to HIV-infected infants
identified. The EID process was considered complete if infants were tested and HIV results
provided to mothers/family before 7 months of age. During 2007-2009, 1587 mother-infant pairs
were included in three referral hospitals; most infants (n = 1423, 89.7%) were tested for HIV, at a
median age of 1.5 months (IQR, 1.4-1.6). Among them, 51 (3.6%) were HIV-infected. Overall,
1331 (83.9%) completed the process by returning for the result before 7 months (median age:
2.5 months (IQR, 2.4-3.0)). Incomplete process, that is test not performed, or result of test not
provided or provided late to the family, was independently associated with late HIV diagnosis
during pregnancy (adjusted odds ratio (aOR) = 1.8, 95%CI: 1.1 to 2.9, p = 0.01), absence of
PMTCT prophylaxis (aOR = 2.4, 95%CI: 1.4 to 4.3, p = 0.002), and emergency caesarean section
(aOR = 2.5, 95%CI: 1.5 to 4.3, p = 0.001).
CONCLUSIONS
In urban areas of Cameroon, HIV-infected women diagnosed sufficiently early during pregnancy
opt to benefit from EID whatever their socio-economic, marital or disclosure status. Reduction of
non optimal diagnosis process should focus on women with late HIV diagnosis during
pregnancy especially if they did not receive any PMTCT, or if complications occurred at
delivery.
28
JAMA. 2011 Jul 6;306(1):70-8.
Association of prenatal and postnatal exposure to lopinavir-ritonavir and
adrenal dysfunction among uninfected infants of HIV-infected mothers.
Simon A, Warszawski J, Kariyawasam D, Le Chenadec J, Benhammou V, Czernichow
P, Foissac F, Laborde K, Tréluyer JM, Firtion G,Layouni I, Munzer M, Bavoux F, Polak
M, Blanche S; ANRS French Perinatal Cohort Study Group.
CONTEXT
Lopinavir-ritonavir is a human immunodeficiency virus 1 (HIV-1) protease inhibitor boosted by
ritonavir, a cytochrome p450 inhibitor. A warning about its tolerance in premature newborns was
recently released, and transient elevation of 17-hydroxyprogesterone (17OHP) was noted in 2
newborns treated with lopinavir-ritonavir in France.
OBJECTIVE
To evaluate adrenal function in newborns postnatally treated with lopinavir-ritonavir.
DESIGN, SETTING, AND PARTICIPANTS
Retrospective cross-sectional analysis of the database from the national screening for
congenital adrenal hyperplasia (CAH) and the French Perinatal Cohort. Comparison of HIV-1uninfected newborns postnatally treated with lopinavir-ritonavir and controls treated with
standard zidovudine.
MAIN OUTCOME MEASURES
Plasma 17OHP and dehydroepiandrosterone-sulfate (DHEA-S) concentrations during the first
week of treatment. Clinical and biological symptoms compatible with adrenal deficiency.
RESULTS
Of 50 HIV-1-uninfected newborns who received lopinavir-ritonavir at birth for a median of 30
days (interquartile range [IQR], 25-33), 7 (14%) had elevated 17OHP levels greater than 16.5
ng/mL for term infants (>23.1 ng/mL for preterm) on days 1 to 6 vs 0 of 108 controls having
elevated levels. The median 17OHP concentration for 42 term newborns treated with lopinavirritonavir was 9.9 ng/mL (IQR, 3.9-14.1 ng/mL) vs 3.7 ng/mL (IQR, 2.6-5.3 ng/mL) for 93 term
controls (P < .001). The difference observed in median 17OHP values between treated
newborns and controls was higher in children also exposed in utero (11.5 ng/mL vs 3.7 ng/mL;
P < .001) than not exposed in utero (6.9 ng/mL vs 3.3 ng/mL; P = .03). The median DHEA-S
concentration among 18 term newborns treated with lopinavir-ritonavir was 9242 ng/mL (IQR,
1347-25,986 ng/mL) compared with 484 ng/mL (IQR, 218-1308 ng/mL) among 17 term controls
(P < .001). The 17OHP and DHEA-S concentrations were positively correlated (r = 0.53; P =
.001). All term newborns treated with lopinavir-ritonavir were asymptomatic, although 3
premature newborns experienced life-threatening symptoms compatible with adrenal
insufficiency, including hyponatremia and hyperkalemia with, in 1 case, cardiogenic shock. All
symptoms resolved following completion of the lopinavir-ritonavir treatment.
CONCLUSION
Among newborn children of HIV-1-infected mothers exposed in utero to lopinavir-ritonavir,
postnatal treatment with a lopinavir-ritonavir-based regimen, compared with a zidovudine-based
regimen, was associated with transient adrenal dysfunction.
29
J Acquir Immune Defic Syndr. 2011 Oct 1;58(2):e43-6.
Seronegativation in early treated HIV-infected infants: frequency and
potential implications on care and follow-up in a resource-limited country.
Kfutwah AK, Tejiokem MC, Ateba FN, Ndongo JA, Penda IC, Ngoupo PA, Tchendjou
P, Chewa G, Boisier P, Rouzioux C, Warszawski J, Faye A; ANRS 12140-Pediacam Study
Group.
INTRODUCTION
Based on the high mortality rates observed in HIV-infected children during the first 2 years of life, the World Health
Organization (WHO) recommends early diagnosis and early initiation of highly active antiretroviral therapy
(HAART).1 A pediatric study (ANRS 12140-Pediacam) was launched in Cameroon in November 2007 with the aim
to evaluate the feasibility and efficacy, in routine practice, of early HAART offered systematically to HIV-infected
infants before 7 months of age.
One of the Pediacam, HIV-infected early treated infant presenting with fever was examined, in an outpatient clinic,
by a medical practitioner not informed of the therapeutic management and follow-up of the child. Considering the
mother's HIV status and the fact that the child was 15 months old, the practitioner after emergency handling opted
for a serological test to confirm the child's HIV status. The infant's HIV rological test result was negative, a situation
that subsequently created some misapprehensions.
We report this case and others in the Pediacam study, with an objective to assess the frequency of seronegativity
among HIV-infected infants who were treated early with HAART.
METHODS
The ANRS-Pediacam study is coordinated by the Centre Pasteur of Cameroon and ongoing in 3 referral hospitals:
the Mother and Child Centre of the Chantal Biya Foundation and the Essos Hospital Centre both in Yaounde and
the Laquintinie Hospital in Douala. Four groups of children participate in this study, and among them, 3 groups are
recruited from birth (or before the eighth day of life) and followed up according to the National Expanded
Programme on Immunization schedule. These groups comprise HIV-infected children diagnosed at 6 weeks, HIV
uninfected children born to HIV-positive mothers, and HIV-negative children born to HIV-negative mothers. The
fourth group comprises HIV-infected children not followed up from birth but diagnosed before 7 months. Early HIV
diagnosis was performed by real-time HIV-RNA PCR (Biocentric HIV Viral Load; Biocentric, Bandol, France) using
an in-house protocol (ANRS AC 11/12 working group).2A positive or indeterminate test result was confirmed with
another sample. Systematic early initiation of HAART was offered to all HIV-infected infants identified. Consent
from the infants' parents was obtained before inclusion. Ethical clearance was obtained from the Cameroon
National Ethics Committee.
HIV-infected children were tested at 15 months or above for the assessment of HIV circulating antibodies. This
serological testing comprises a fourth-generation test (AxSYM HIV Ag/Ab Combo assay; Abbott Diagnostics,
Wiesbaden, Germany) as the first test in the algorithm. Initial sample/cut-off values >1.00 are reactive, whereas
values 0.90 to ≤1.00 are considered gray zone values. A result of <0.90 is considered negative, and no further
testing is required. Therefore, in this study, seronegativity was defined as HIV-infected infants, aged 15 months or
older, with AxSYM blood sample/cut-off values <0.90.
Seronegative samples were also tested using the “2 rapid tests” algorithm recommended by the WHO in economic
restraint countries.3HIV-1 Western blot (Bio-Rad, Marnes-la-Coquette, France) was also used to characterize these
samples. Repeated HIV seronegative samples were confirmed for HIV infections by HIV1-DNA PCR (Biocentric).
RESULTS
Among the 57 HIV-infected infants who initiated HAART at a median age of 3.7 months (interquartile range: 3.15.9) and tested serologically at a median age of 19.4 months (interquartile range: 18.1-21.9), 15 (26.3%, 95%
confidence interval: 15.5 to 39.7) were seronegative with AxSYM and 6 (10.3%) were indeterminate for HIV
antibody analysis. Testing these 15 seronegative samples with the 2 rapid tests algorithm, it was observed that in
concordance with AxSYM, 6 of 15 infants were negative with both rapid tests used, and none of the samples could
be concluded positive by Western blotting (Table 1). Others had equivocal results with at least one of the 2 rapid
tests being negative (data not shown). In Table 1, we present the 6 children who were AxSYM negative and 2 rapid
test negative. Serotyping of these samples before first HIV PCR diagnosis revealed that they were all of HIV-1
group M serotype. Results of viral load assays performed while children received HAART and a few months (mean
3.3 months) before serological testing showed that 5 of 6 infants had very low to undetectable viral loads (<2.5-2.7
30
log10 copies/mL), whereas only 1 infant had a high viral load (5.9 log10 copies/mL). Corresponding CD4 cell
percentages ranged from 22% to 54%. Five infants were tested positive for HIV-DNA at the time of serological
analysis, and 1 infant was not tested due to sample exhaustion. At the time of these testing, the infants had been
on treatment for an average of 15.8 months.
DISCUSSION
The WHO strongly recommends that serological diagnosis in children aged 18 months or older be performed
according to the standard diagnostic algorithm used in adults.1 Two case reports of HIV-infected, seronegative, and
treatment-naive children have been published.4,5Luzuriaga et al6 also reported seronegativity in a cohort of 17 HIVinfected infants put on treatment before 3 months and tested for HIV antibodies at 16 months. To our knowledge,
this is the first study in a resource-limited setting that describes seronegativity in HIV-infected infants on
antiretroviral treatment.
In this study, 26.3% (15 of 57) of HIV-infected infants on HAART were repeatedly seronegative by AxSYM, a test
that has been evaluated on variant strains and seroconverting patients.7 The high specificity and sensitivity
observed (>99.9%, respectively) has encouraged its widespread use in routine HIV diagnosis.8 In simulation of
what could be obtained, if these children are consulted in a remote health facility, we diagnosed 6 unequivocal
seronegative samples using the 2 rapid tests algorithm.3 Determine and Oraquick rapid tests used in this study
meet the WHO standards of sensitivity and specificity.9,10. All samples in this study were serotyped as HIV-1 group
M, that is, there were no divergent HIV strains that could lead to possible misdiagnosis.
The viral loads of the 2 cases of HIV-positive seronegative infants already described4,5 were >6 and 5.8 log10 copies
per milliliter at the age of 2 and 4 months, respectively. This profile combining high HIV viral load and seronegativity
seem to be in agreement with only 1 infant in our study (infant 4: 18.8 months old, viral load of 5.9 log10copies/mL).
However, it should be noted that, in this study, viral load analysis was done on an average of 3 months before
serological analysis and therefore does not exclude changes in viral load before serodiagnosis because the child is
on HAART. Generally, seronegativity has been observed in patients presenting with symptoms that meet AIDS
defining cases. Conversely, low/undetectable viral load and seronegativity observed by Luzuriaga et al6 are
understandably in line with 5 of 6 seronegative infants in this study. In both studies, the role of HAART in drastically
reducing the viral loads cannot be underestimated. Furthermore, some studies in adults have shown HIV patients
treated early in the course of their infections with ARV therapy that became seronegative,11 a situation similar to
ours, albeit in adults. We could postulate that the early exposure of these infants to HAART led to a rapid
virological suppression and consequently the lack of viral antigen to illicit immune response.
Similarities have been observed in the kinetics of plasma HIV-1-specific antibody clearance in infants who received
early therapy and uninfected infants born to HIV-1-seropositive women, suggesting that these infants did not
actively generate HIV-1-specific antibodies.4Other immunological tests, especially antibody production assays and
kinetics, in these infants could further elucidate this observation in our study sites.
Western blotting showed that just 1 infant had an envelope glycoprotein band (gp160), whereas others had only 1
or 2 bands representing the internal proteins. The nonreactivity to serological tests could be due to the fact that
these children did not have the circulating envelope proteins commonly used in serological tests such as
gp41.5Other studies have shown that the nonexpression of envelope glycoprotein in some patients could lead to
the seronegativity observed in some rapid tests.12 Children in this study are undoubtedly infected with HIV as
shown by HIV-RNA PCRs carried out before treatment and the HIV-DNA PCRs carried out concomitantly with HIVspecific antibody testing.
Our observation of HIV seronegativation in 26.3% (15 of 57) of HIV-infected infants suggests that this phenomenon
is not uncommon. This has been heightened by our experience of a known HIV-positive child on HAART that was
tested seronegative in another hospital department and the ensuing misapprehensions that were generated. If
caution is not exercised, the interpretation of such serological tests could be misleading in resource limited settings
like ours. Importantly, in settings where virological tests are not available, WHO recommends an early presumptive
therapy in infants based on clinical findings and a positive serological test with a serological confirmation of HIV
infection after 15 months of age.1 Our data suggest that, this serological confirmation could be inappropriate even
when performed above 15 months of age and could lead to inappropriate treatment interruptions in HIV-infected
infants receiving early treatment.
31
Lancet. 2011 May 7;377(9777):1580-7.
Risk of triple-class virological failure in children with HIV: a retrospective
cohort study.
Pursuing Later Treatment Options II (PLATO II) project team for the Collaboration of
Observational HIV Epidemiological Research Europe (COHERE), Castro H, Judd A, Gibb
DM, Butler K, Lodwick RK, van Sighem A, Ramos JT, Warsawski J, Thorne C, NogueraJulian A, Obel N, Costagliola D, Tookey PA, Colin C, Kjaer J, Grarup J, Chene G, Phillips
A.
BACKGROUND
In adults with HIV treated with antiretroviral drug regimens from within the three original drug
classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs],
and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological
suppression can be achieved in most people, even in areas where access is restricted to drugs
from these classes. It is unclear whether this is the case for children, the group who will need to
maintain viral suppression for longest. We aimed to determine the rate and predictors of tripleclass virological failure to the three original drugs classes in children.
METHODS
In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of tripleclass virological failure was studied in children infected perinatally with HIV who were aged less
than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and
2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors
of triple-class virological failure after ART initiation.
FINDINGS
Of 1007 children followed up for a median of 4·2 (IQR 2·4-6·5) years, 237 (24%) were tripleclass exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viralload measurement less than 500 copies per mL. Incidence of triple-class virological failure after
ART initiation increased with time, and risk by 5 years after ART initiation was 12·0% (95% CI
9·4-14·6). In multivariate analysis, older age at ART initiation was associated with increased risk
of failure (p=0·02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavirboosted protease inhibitor, the rate of failure was higher than in adults with heterosexually
transmitted HIV (hazard ratio 2·2 [95% CI 1·6-3·0, p<0·0001]).
INTERPRETATION
Findings highlight the challenges of attaining long-term viral suppression in children who will be
taking life-long ART. Early identification of children not responding to ART, adherence support,
particularly for children and adolescents aged 13 years or older starting ART, and ART
simplification strategies are all needed to attain and sustain virological suppression.
32
J Acquir Immune Defic Syndr. 2011 Jun 1;57(2):126-35.
Previous antiretroviral therapy for prevention of mother-to-child
transmission of HIV does not hamper the initial response to PI-based
multitherapy during subsequent pregnancy.
Briand N, Mandelbrot L, Blanche S, Tubiana R, Faye A, Dollfus C, Le Chenadec
J, Benhammou V, Rouzioux C, Warszawski J; ANRS French Perinatal Cohort (ANRS EPFCO-01).
BACKGROUND
Few data are available on the possible long-term negative effects of a short exposure to
antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT).
OBJECTIVE
To determine whether ART for PMTCT, discontinued after delivery, affects the virological
response to highly active antiretroviral therapy (HAART) administered during subsequent
pregnancies.
METHODS
All current pregnancies of HIV-1-infected women enrolled in the French Perinatal Cohort (ANRS
CO-01 EPF) between 2005 and 2009 and not receiving ART at the time of conception were
eligible. We studied the association between history of exposure to ART during a previous
pregnancy and detectable viral load (VL) under multitherapy at current delivery (VL ≥ 50
copies/mL).
RESULTS
Among 1116 eligible women, 869 were ART naive and 247 had received PMTCT during a
previous pregnancy. Previous ART was protease inhibitor (PI)-based HAART in 48%, non-PIbased HAART in 4%, nucleoside reverse transcriptase inhibitor bitherapy in 19% and
zidovudine monotherapy in 29% of the women. At current pregnancy, women with or without
prior exposure to ART had similar CD4 cell counts and VL before ART initiation. PI-based
HAART was initiated in 90% of the women. VL was undetectable (<50 copies/mL) at delivery in
65% of previously ART-naive women, 72% of women previously exposed to HAART, 62%
previously exposed to bitherapy, and 67% previously exposed to monotherapy for prophylaxis
(P = 0.42). Detectable VL was not associated with previous exposure in multivariate analysis
(adjusted OR for previous versus no previous exposure to ART: 0.92; 0.95% confidence
interval: 0.59 to 1.44).
CONCLUSIONS
Efficacy of PI-based combinations is not decreased in women previously exposed to various
regimens of antiretroviral PMTCT.
33
Pediatr Infect Dis J. 2011 Aug;30(8):684-8
Lopinavir/ritonavir-based antiretroviral therapy in human immunodeficiency
virus type 1-infected naive children: rare protease inhibitor resistance
mutations but high lamivudine/emtricitabine resistance at the time of
virologic failure.
Frange P, Briand N, Avettand-fenoel V, Veber F, Moshous D, Mahlaoui N, Rouzioux
C, Blanche S, Chaix ML.
BACKGROUND
Lopinavir/ritonavir (LPV/r) is now the protease inhibitor regimen of choice in the first-line
antiretroviral therapy for children <6 years of age.
METHODS
We included all the human immunodeficiency virus (HIV) type 1-infected highly active
antiretroviral therapy (HAART)-naive children who started an LPV/r-based regimen between
2000 and 2009 at the Necker Hospital (Paris, France). Virologic failure (VF) was defined as an
HIV-RNA ≥50 copies/mL. Resistance genotypic test was performed in case of VF.
RESULTS
A total of 43 children were included at a median age of 4.8 years (1.8-8.0). Median level of HIV
RNA and percentage of CD4 cell count was 5.5 log₁₀ copies/mL (4.6-6) and 15% (8-27.5),
respectively. HAART included LPV/r and 2 nucleoside reverse-transcriptase inhibitors, mainly
lamivudine (3TC), zidovudine, and/or abacavir. The median follow-up period was 36 months
(18-72). Less than 50 copies/mL of HIV RNA was observed in 46%, 67%, and 70% of the
children at months 6, 9, and 12, respectively. In all, 20 children (46.5%) experienced a VF. The
risk factors of primary VF were a young age and a low socioeconomic status. The genotypic
resistance test, performed for 18 of 20 children with VF, revealed 1 LPV/r-resistant virus and
protease inhibitor-related major mutations without LPV/r resistance in 2 other children. Of the 18
children with VF, 15 received a 3TC-based HAART: 12 of 15 (80%) harbored a 3TC-resistant
virus. No virus resistant to zidovudine or abacavir was found.
CONCLUSION
In all, 70% of HAART-naive children had virologic success at month 12. The selection of LPVresistant strains was a rare event. A high rate of selection of 3TC-mutations strengthens the
recommendation to prefer a first-line 3TC-sparing regimen, particularly for children with risk
factors of poor adherence.
34
Clin Infect Dis. 2010 Oct 1;51(7):833-43.
Mother-to-Child Transmission of HIV-2 Infection from 1986 to 2007 in the
ANRS French Perinatal Cohort EPF-CO1
M. Burgard, C. Jasseron, S. Matheron, F. Damond, K. Hamrene, S. Blanche, A. Faye, C.
Rouzioux, J. Warszawski, L. Mandelbrot, and the ANRS French Perinatal Cohort EPF-CO1
BACKGROUND
Management of pregnant women with human immunodeficiency virus (HIV) type 2 infection
remains unclear because of its low prevalence and important differences from HIV-1.
METHODS
Pregnant women monoinfected with HIV-2 or HIV-1 and their infants enrolled in the prospective,
national, multicenter French Perinatal Cohort between 1986 and 2007.
RESULTS
Overall, 2.6% (223/8660) of mothers were infected with HIV-2, and they accounted for 3.1%
(367/11841) of the total births. Most were born in sub-Saharan Africa. A higher proportion of
HIV-2-infected mothers than HIV-1-infected mothers had no symptoms, had received no
antiretroviral threrapy at conception (85.9% vs 66.7%), and had received no antiretroviral
therapy during pregnancy (42.8% vs 19.9%), particularly highly active antiretroviral therapy
(HAART) (79.7% vs 46.1%), and they had higher CD4 cell counts near delivery (median, 574 vs
452 cells/mm3; P < .01). If antiretroviral therapy was used, it was started at a later gestational
age for HIV-2-infected mothers (median, 28 vs 25 weeks; P < .01). HIV-2-infected mothers were
more likely to deliver vaginally (67.9% vs 49.3%) and to breastfeed (3.6% vs 0.6%; P < .01),
and their infants less frequently received postexposure prophylaxis. In the period 2000–2007,
the proportion with viral load <100 copies/mL at delivery was 90.5% of HIV-2-infected mothers,
compared with 76.2% of HIV-1-infected mothers (P = .1). There were 2 cases of transmission: 1
case in 1993 occurred following maternal primary infection, and the other case occurred
postnatally in 2002 and involved a mother with severe immune deficiency. The mother-to-child
transmission rate for HIV-2 was 0.6% (95% confidence interval, 0.07%–2.2%).
CONCLUSIONS
Care for HIV-2-infected pregnant women rests on expert opinion. The mother-to-child
transmission residual rate (0.07%–2.2%) argues for systematic treatment: protease inhibitorbased HAART for women requiring antiretroviral therapy or for primary infection and simplified
prevention of mother-to-child transmission in other instances.
35
Clin Infect Dis. 2010 Jul 15;51(2):214-24
Long-Term Outcomes in Adolescents Perinatally Infected with HIV-1 and
Followed Up since Birth in the French Perinatal Cohort (EPF/ANRS CO10)
C. Dollfus, J. Le Chenadec, A. Faye, S. Blanche, N. Briand, C. Rouzioux, and J.
Warszawski
BACKGROUND
Increasing numbers of children perinatally infected with human immunodeficiency virus (HIV)
are reaching adolescence, largely because of advances in treatment over the past 10 years, but
little is known about their current health status. We describe here the living conditions and
clinical and immunovirologic outcomes at last evaluation among this pioneering generation of
adolescents who were born before the introduction of prophylaxis for vertical transmission and
whose infections were diagnosed at a time when treatment options were limited.
METHODS
The eligible population consisted of HIV-1—infected children who were born before December
1993 and who were included at birth in the prospective national French Perinatal Cohort
(EPF/ANRS CO10).
RESULTS
Of the 348 eligible children, 210 (60%; median age, 15 years) were still alive and regularly
followed up. Current treatment was highly active antiretroviral therapy (HAART) in 77% and 2
nucleoside analogues in 5.0%; 16% had stopped treatment, and 2% had never been treated.
The median CD4 cell count was 557 cells/µL, and 200 cells/µL was exceeded in 94% of
patients. The median viral load was 200 copies/mL. Viral load was undetectable in 43% of the
adolescents and in 54.5% of those receiving HAART. Median height, weight, and body mass
index were similar to French reference values for age, and school achievement was similar to
nationwide statistics. Better immunologic status was associated with being younger and with
having begun HAART earlier. Undetectable viral load was associated with maternal geographic
origin and current HAART.
CONCLUSIONS
Given the limited therapeutic options available during the early years of these patients' lives and
the challenge presented by treatment adherence during adolescence, the long-termoutcomes
among this population are encouraging.
36
Clin Infect Dis. 2010 ;50(4): 585-96
Factors Associated with Mother-to-Child Transmission of HIV-1 Despite a
Maternal Viral Load <500 Copies/mL at Delivery: A Case-Control Study
Nested in the French Perinatal Cohort (EPF-ANRS CO1)
Roland Tubiana, Jerome Le Chenadec, Christine Rouzioux, Laurent Mandelbrot, Karima
Hamrene, Catherine Dollfus, Albert Faye, Constance Delaugerre, Stephane Blanche,
Josiane Warszawski, and ANRS French Perinatal Cohort (ANRS CO1/CO11)
BACKGROUND
The rate of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1
is as low as 0.5% in non–breast-feeding mothers who delivered at term while receiving
antiretroviral therapy with a plasma viral load <500 copies/mL. This situation accounted for 20%
of the infected children born during the period 1997–2006 in the French Perinatal Cohort. We
aimed to identify factors associated with such residual transmission risk.
METHODS
We performed a case-control study nested in the aforementioned subpopulation of the French
Perinatal Cohort.
RESULTS
Nineteen case patients (transmitters) and 60 control subjects (nontransmitters) were included.
Case patients and control subjects did not differ by geographical origin, gestational age at HIV
diagnosis, type of antiretroviral therapy received, or elective Cesarean delivery. Case patients
were less often receiving treatment at the time that they conceived pregnancy than control
subjects (16% vs 45%; P=.017). A lower proportion of case patients had a viral load <500
copies/mL, compared with control subjects, at 14 weeks (0% vs 38.1%; P=.02), 28 weeks (7.7%
vs 62.1%; P=.005), and 32 weeks: (21.4% vs 71.1%; P=.004). The difference remained
significant when we restricted analysis to the 10 of 16 intrapartum transmission cases. In a
multivariate analysis at 30±4 weeks adjusted for viral load, CD4+ T cell count, and time at
antiretroviral therapy initiation, viral load was the only factor independently associated with
MTCT of HIV (adjusted odds ratio, 23.2; 95% confidence interval, 3.5–553; P<.001).
CONCLUSIONS
Early and sustained control of viral load is associated with a decreasing residual risk of MTCT of
HIV-1. Guidelines should take into account not only CD4+ T cell count and risk of preterm
delivery, but also baseline HIV-1 load for deciding when to start antiretroviral therapy during
pregnancy.
37
AIDS. 2010 Jul 17;24(11):1771-6
Late postnatal HIV infection in children born to HIV-1-infected mothers in a
high-income country.
Frange, Pierre; Burgard, Marianne; Lachassinne, Eric; le Chenadec, Jerome; Chaix,
Marie-Laure; Chaplain, Chantal; Warszawski, Josiane; Dollfus, Catherine; Faye, Albert;
Rouzioux, Christine; Blanche, Stephane; for the ANRS French Perinatal Cohort Study
Group
OBJECTIVE
To evaluate the risk of late postnatal HIV-1 infection in nonbreastfed children enrolled in the French
ANRS Cohort CO01 (EPF).
METHODS
The EPF cohort has prospectively enrolled HIV-infected mother/child pairs with a low proportion of
known breastfeeding (<0.2%). Children were followed until they were 24 months old, with HIV-1
DNA/RNA PCR tests performed at birth, M1, M3 and M6 and a late serology at 18-24 months. This
substudy included 4539 children who were uninfected at the age of 6 months in 1984-2005.
RESULTS
Five children were late diagnosed with HIV-1 infection despite negative PCR tests until 6 months. In
three cases, the infection was diagnosed between 14 and 18 months. The other infections were
diagnosed at 10 and 12 years of age because of AIDS-defining symptoms; their last (negative)
serologies were performed at 19 and 9 months, respectively. A phylogenetic study performed in the
latest case revealed a strong homology between the mother and child strains. No known mode of viral
transmission (including breastfeeding or use of premasticated food) could be found. However, we
observed previously reported risk factors for intrafamilial HIV-1 transmission: poor socioeconomic
backgrounds and sustained HIV-1 viremia in the mothers during the follow-up of their children.
CONCLUSION
Late postnatal HIV-1 infection can rarely be diagnosed in the absence of known breastfeeding in highincome countries. Our results highlight the need for a maintained close follow-up of the noninfected
children even after 6 months, especially when there are risk factors for intrafamilial viral transmission.
38
Arch Intern Med. 2010 Mar 8;170(5):410-9
Triple-Class Virologic Failure in HIV-Infected Patients Undergoing
Antiretroviral Therapy for Up to 10 Years.
The PLATO II Project Team for the Collaboration of Observational HIV Epidemiological
Research Europe (COHERE) Group
BACKGROUND
Life expectancy of people with human immunodeficiency virus (HIV) is now estimated to
approach that of the general population in some successfully treated subgroups. However, to
attain these life expectancies, viral suppression must be maintained for decades.
METHODS
We studied the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of
Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral
therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a
ritonavir-boosted protease inhibitor (PI/r) from 1998 onwards. We also focused on TCVF in
patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed.
RESULTS
Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980
developed TCVF (2.1%). By 5 and 9 years after starting ART, an estimated 3.4% (95%
confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively,
had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but
plateaued thereafter. There was no significant difference in the risk of TCVF according to
whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r
regimen as second-line therapy, 46% of patients had developed TCVF.
CONCLUSION
The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not
appear to diminish over time from starting ART. If this trend continues, many patients are likely
to need newer drugs to maintain viral suppression. The rate of TCVF from the start of a PI/r
regimen after NNRTI failure provides a comparator for studies of response to second-line
regimens in resource-limited settings.
39
Retrovirology. 2009 Sep 19;6:85
Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and
long-term outcome.
Constance Delaugerre, Marie-Laure Chaix, Stephane Blanche, Josiane Warszawski,
Dorine Cornet, Catherine Dollfus, Veronique Schneider, Marianne Burgard, Albert Faye,
Laurent Mandelbrot, Roland Tubiana, Christine Rouzioux, and the ANRS French Perinatal
Cohort
BACKGROUND
Primary-HIV-1-infection in newborns that occurs under antiretroviral prophylaxis that is a high
risk of drug-resistance acquisition. We examine the frequency and the mechanisms of
resistance acquisition at the time of infection in newborns.
PATIENTS and METHODS
We studied HIV-1-infected infants born between 01 January 1997 and 31 December 2004 and
enrolled in the ANRS-EPF cohort. HIV-1-RNA and HIV-1-DNA samples obtained perinatally
from the newborn and mother were subjected to population-based and clonal analyses of drug
resistance. If positive, serial samples were obtained from the child for resistance testing.
RESULTS
Ninety-two HIV-1-infected infants were born during the study period. Samples were obtained
from 32 mother-child pairs and from another 28 newborns. Drug resistance was detected in 12
newborns (20%): drug resistance to nucleoside reverse transcriptase inhibitors was seen in 10
cases, non-nucleoside reverse transcriptase inhibitors in two cases, and protease inhibitors in
one case. For 9 children, the detection of the same resistance mutations in mothers' samples (6
among 10 available) and in newborn lymphocytes (6/8) suggests that the newborn was initially
infected by a drug-resistant strain. Resistance variants were either transmitted from mother-tochild or selected during subsequent temporal exposure under suboptimal perinatal prophylaxis.
Follow-up studies of the infants showed that the resistance pattern remained stable over time,
regardless of antiretroviral therapy, suggesting the early cellular archiving of resistant viruses.
The absence of resistance in the mother of the other three children (3/10) and neonatal
lymphocytes (2/8) suggests that the newborns were infected by a wild-type strain without longterm persistence of resistance when suboptimal prophylaxis was stopped.
CONCLUSION
This study confirms the importance of early resistance genotyping of HIV-1-infected newborns.
In most cases (75%), drug resistance was archived in the cellular reservoir and persisted during
infancy, with or without antiretroviral treatment. This finding stresses the need for effective
antiretroviral treatment of pregnant women.
40
CID. 2009 Jun 1;48(11):1516-25.
Decreased risk of congenital cytomegalovirus (CMV) infection in children
born to HIVinfected mothers in the era of highly active antiretroviral therapy
(HAART).
Guibert G, Warszawski J, Le Chenadec J, Blanche S, Benmebarek Y, Mandelbrot L,
Tubiana R, Rouzioux C, Leruez-Ville M; on behalf of the French Perinatal Cohort (EPF).
BACKGROUND
We evaluated the prevalence of congenital CMV infection before and after HAART availability in
neonates born to HIV-infected mothers. We also identified maternal risk factors associated with
in utero CMV transmission.
METHODS
Routine screening for congenital CMV infection was carried out between 1993 and 2004 in
children born to the HIV-infected mothers included in the EPF French Perinatal Cohort (ANRS
CO1/10/11). Interpretable tests on urine samples collected within the first ten days of life were
available for 4797 of the 7563 liveborn infants. Prevalence was estimated according to different
periods. Univariate and multivariate logistic regression analyses were carried out to identify
factors associated with transmission in HAART era.
RESULTS
The overall prevalence of CMV infection was 2.3% of live-born children (95% CI:1.9–2.8). It was
higher in HIV-infected neonates (10.3%; 95% CI: 5.6-17.0) than in HIVuninfected neonates
(2.2%, 95% CI:1.8–2.7), p<0.01. The prevalence of CMV infection decreased over time, from
3.5% (1997-98) to 1.2% (2003-04), in HIV-uninfected neonates. Delivery period, maternal age,
time at antiretroviral treatment initiation and maternal CD4+ count <200/mm3 close to delivery
were independently associated with CMV infection in logistic regression. The proportion of
symptomatic CMV infections was 23.1% in HIVinfected newborns and 6.7% in HIV-uninfected
neonates.
CONCLUSIONS
The prevalence of congenital CMV infection was high and associated with high morbidity rates
in HIV-infected neonates. Conversely, it decreased over time in neonates not infected with HIV,
reaching levels similar to those observed in the general population, following the introduction
and increasing use of HAART for preventing mother-to-child HIV transmission.
41
AIDS. 2009 Jun 19;23(10):1235-43.
No relation between in utero exposure to highly active antiretroviral therapy
and intrauterine growth retardation.
N Briand, L. Mandelbrot, J. Le Chenadec, R. Tubiana, J.P. Teglas, A. Faye, C. Dollfus, C.
Rouzioux, S. Blanche, J. Warszawski; for the ANRS French Perinatal Cohort.
BACKGROUND
The use of highly active antiretroviral therapies (HAART) during pregnancy is now standard
care to prevent mother-to-child HIV transmission in developed countries. There is controversy
about its impact on low birthweight.
OBJECTIVE
To evaluate the impact of ART during the pregnancy on birthweight, lenght and head
circumference.
METHODS
The study was performed in uninfected infants born to HIV-1-infected mothers, enrolled from
1990 to 2006 in the ANRS French Perinatal Cohort CO1. We excluded mothers who used illicit
drugs during pregnancy or had no prenatal care before the third trimester, twins and stillbirths.
We used Z-scores adjusted for gestational age and sex.
RESULTS
In 8192 mother-infant pairs, the mean birthweight Z-scores increased between 1990 and 1997
and then remained stable until 2006. There was no significant relation between the type of ART
and the proportion of small-for-gestational age (birthweight Z-score < -2 SD), which was 4%
overall. Infants exposed to HAART compared with monotherapy had a lower mean birthweight
Z-scores (difference: -0.09, 95%CI: -0.15 to -0.02), however there was no difference between
HAART exposure in 2005-2006 and monotherapy in 1999-2004 which corresponded to
standard care during each period, respectively. Height or head circumference Z-scores were not
associated with ART exposure. Among pregnancies with HAART, there was no relation
between the duration and type of therapy and the anthropometric parameters.
CONCLUSION
Our findings in a large cohort suggest that HAART during pregnancy does not increase the
incidence of infants who are small for gestational age.
42
AIDS. 2009 23(5):597-604
Effect of early antiretroviral therapy on the risk of AIDS/death in HIV-infected
infants.
Goetghebuer T, Haelterman E, Le Chenadec J, Dollfus C, Gibb D, Judd A, Green H, Galli
L, Ramos JT, Giaquinto C, Warszawski J, Levy J; for the European Infant Collaboration
group.
OBJECTIVE
In the absence of treatment, rapid progression to AIDS occurs in approximately 20% of HIV-1infected infants over the first year of life. The prognosis of these children has considerably
improved with highly active antiretroviral therapy. As data from well resourced countries are
lacking, the objective of this collaborative study was to evaluate the impact of early treatment in
vertically infected infants.
DESIGN
Children born to HIV-infected mothers between 1 September 1996 and 31 December 2004, who
were diagnosed with HIV and free of AIDS before 3 months, were eligible. Demographics and
pregnancy data, details of antiretroviral therapy, and clinical outcome were collected from 11
European countries
METHODS
The risk of AIDS or death, by whether or not an infant started treatment before 3 months of age,
was estimated by Kaplan-Meier survival analysis and Cox proportional hazards models.
RESULTS: Among 210 children, 21 developed AIDS and three died. Baseline characteristics of
the 124 infants treated before 3 months were similar to those of the 86 infants treated later. The
risk of developing AIDS/death at 1 year was 1.6 and 11.7% in the two groups, respectively (P <
0.001). Deferring treatment was associated with increased risk of progression [crude hazard
ratio 5.0; 95% confidence interval (CI) 2.0-12.6; P = 0.001] that persisted after adjusting for
cohort in multivariate models (adjusted hazard ratio 3.0; 95% CI 1.2-7.9; P = 0.021)
CONCLUSION
In HIV-1 vertically infected infants, starting antiretroviral therapy before the age of 3 months is
associated with a significant reduction in progression to AIDS and death.
43
J Med Virol. 2009 Feb;81(2):217-23.
LTR real-time PCR for HIV-1 DNA quantitation in blood cells for early
diagnosis in infants born to seropositive mothers treated in HAART area
(ANRS CO 01).
Avettand-Fènoël V, Chaix ML, Blanche S, Burgard M, Floch C, Toure K, Allemon MC,
Warszawski J, Rouzioux C; French Pediatric Cohort Study ANRS-CO 01 Group.
HIV-1 diagnosis in babies born to seropositive mothers is one of the challenges of HIV
epidemics in children. A simple, rapid protocol was developed for quantifying HIV-1 DNA in
whole blood samples and was used in the ANRS French pediatric cohort in conditions of
prevention of mother-to-child transmission. A quantitative HIV-1 DNA protocol (LTR real-time
PCR) requiring small blood volumes was developed. First, analytical reproducibility was
evaluated on 172 samples. Results obtained on blood cell pellets and Ficoll-Hypaque separated
mononuclear cells were compared in 48 adult HIV-1 samples. Second, the protocol was applied
to HIV-1 diagnosis in infants in parallel with plasma HIV-RNA quantitation. This prospective
study was performed in children born between May 2005 and April 2007 included in the ANRS
cohort. The assay showed good reproducibility. The 95% detection cut-off value was 6
copies/PCR, that is, 40 copies/10(6) leukocytes. HIV-DNA levels in whole blood were highly
correlated with those obtained after Ficoll-Hypaque separation (r = 0.900, P < 0.0001). A total of
3,002 specimens from 1,135 infants were tested. The specificity of HIV-DNA and HIV-RNA
assays was 100%. HIV-1 infection was diagnosed in nine infants before age 60 days. HIV-DNA
levels were low, underlining the need for sensitive assays when highly active antiretroviral
therapy (HAART) has been given. The performances of this HIV-DNA assay showed that it is
adapted to early diagnosis in children. The results were equivalent to those of HIV-RNA assay.
HIV-DNA may be used even in masked primary infection in newborns whose mothers have
received-HAART.
44
Am J Obstet Gynecol. 2009 Feb;200(2):160.e1-9.
Amniocentesis and mother-to-child human immunodeficiency virus
transmission in the Agence Nationale de Recherches sur le SIDA et les
Hépatites Virales French Perinatal Cohort.
Mandelbrot L, Jasseron C, Ekoukou D, Batallan A, Bongain A, Pannier E, Blanche S,
Tubiana R, Rouzioux C, Warszawski J; ANRS French Perinatal Cohort (EPF)
OBJECTIVE
The objective of the study was to investigate whether performing an amniocentesis increased
mother-to-child transmission of human immunodeficiency virus (HIV)-1 (MTCT).
STUDY DESIGN
We studied HIV -1 infected mothers and their children enrolled in the multicenter French
Perinatal HIV Cohort from 1985 to 2006.
RESULTS
One hundred sixty-six amniocenteses were performed among 9302 singleton pregnancies, the
proportion increasing from 1.0% before 2001 to 4.7% in 2005-2006. Use of highly active
antiretroviral therapy (HAART) was more frequent in the amniocentesis group (58.4% vs
33.2%). MTCT tended to be higher in the amniocentesis group, among mothers who received
no antiretroviral agents (25.0%; 3/12 vs 16.2%; 343/2113; P = .41) as well as among mothers
receiving zidovudine monotherapy or a double-nucleoside reverse transcriptase inhibitor
combination (6.1%; 3/49 vs 3.3%; 117/3556; P = .22), but the difference was not significant.
Among 81 mothers receiving HAART, there was no case of MTCT.
CONCLUSION
Our results suggest that amniocentesis is not a major risk factor for mother-to-child transmission
in mothers treated with effective antiretroviral therapy.
45
AIDS. 2008 Oct 18;22(16):2165-77.
Incidence of cancer in children perinatally exposed to nucleoside reverse
transcriptase inhibitors.
Benhammou V, Warszawski J, Bellec S, Doz F, André N, Lacour B, Levine M, Bavoux F,
Tubiana R, Mandelbrot L, Clavel J, Blanche S; ANRS-Enquête Périnatale Française.
CONTEXT
Long-term studies of tolerance to perinatal exposure to antiretroviral nucleoside reverse
transcriptase inhibitors are required, in view of the potential genotoxicity of some of these
molecules.
OBJECTIVE
To evaluate the incidence of cancers in uninfected children born to HIV-infected mothers.
METHOD
Cancers were detected in a nationwide prospective cohort of children born to HIV-infected
mothers by standardized questionnaire during the prospective follow-up period of 2 years;
thereafter, they were detected by spontaneous pharmacovigilance declaration and by
crosschecking data with the national registries of childhood cancer. Standardized incidence
ratio for incidence comparisons with general population.
RESULTS
Ten cases of cancer were detected among the 9127 exposed HIV-uninfected children (median
age: 5.4 years, 53 052 person-years of follow-up). The overall incidence did not differ
significantly from that expected for the general population: 10 cases observed versus 8.9 and
9.6 expected depending on whether 1990-1999 or 2000-2004 national rates were used as
reference [standardized incidence ratio of 1.1 (0.3-1.5) and 1.0 (0.5-1.9)]. Five cases of central
nervous system cancer were observed (standardized incidence ratio of 3.1 [1.0-7.2] P = 0.05
and 2.4 [0.8-5.6], P = 0.12). The relative risk of cancer for children exposed to didanosinelamivudine combination was higher than that for zidovudine monotherapy [hazard ratio: 13.6
(2.5-73.9)].
CONCLUSION
This study did not evidence an overall increase in cancer risk in nucleoside reverse
transcriptase inhibitor exposed children until 5 years of age. Results suggesting associations
with specific nucleoside reverse transcriptase inhibitor combinations need further investigations.
A longer surveillance, including differential analysis of the different cancer sites and various
nucleoside reverse transcriptase inhibitors administered is warranted.
46
AIDS. 2008 Jul 31;22(12):1503-11.
Prevention of mother-to-child HIV transmission: similar access for subSahara African immigrants and for French women?
Jasseron C, Mandelbrot L, Tubiana R, Teglas JP, Faye A, Dollfus C, Le Chenadec J,
Rouzioux C, Blanche S, Warszawski J; ANRS French Perinatal Cohort.
OBJECTIVE
To investigate whether mother-to-child transmission (MTCT) management and rate differed
between African immigrants and French-born women delivering in France.
METHODS
MTCT strategies were studied among human immunodeficiency virus type 1-infected women
delivering between 1984 and 2007 in the multicenter French Perinatal Cohort, according to
geographical origin.
RESULTS
Among 9245 pregnancies (in 7090 women), the proportion of African mothers increased from
12% in 1984-1986 to 64% in 2003-2004. African women had later access to care than French
women, even in recent years (1997-2004). They more often discovered their HIV infection
during pregnancy (40.6 vs. 11.5%, P < 0.001), started prenatal care in the third trimester (14.1
vs. 9.8%, P < 0.001) and started antiretroviral therapy after 32 weeks gestation (7.6 vs. 4.1%, P
< 0.001). The association with late treatment initiation disappeared when adjusted for late HIV
diagnosis and prenatal care (adjusted odds ratio 1.0, 95% confidence interval 0.7-1.4). African
and French women did not differ in terms of access to highly active antiretroviral therapy, nor for
substandard management such as vaginal delivery with uncontrolled viral load, lack of
intrapartum and postpartum treatment or breastfeeding. The MTCT rate was higher for African
than for French women receiving antiretroviral therapy (1.8 vs. 0.8%, P = 0.02), but the
difference was no longer significant after adjustment for main transmission risk factors (adjusted
odds ratio = 1.7, 95% confidence interval 0.8-3.7, P = 0.17). MTCT did not differ among 2110
term deliveries with maternal viral load less than 400 copies/ml, (0.8 vs. 0.6%, P = 0.5).
CONCLUSION
African immigrants more often had late HIV screening in pregnancy than French-born women,
but had similar access to MTCT prevention, once the infection was diagnosed.
47
AIDS. 2008 Jul 31;22(12):1463-73.
Response to combination antiretroviral therapy: variation by age.
Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Study
Group.
OBJECTIVE
To provide information on responses to combination antiretroviral therapy in children,
adolescents and older HIV-infected persons.
DESIGN and SETTING
Multicohort collaboration of 33 European cohorts.
SUBJECTS
Forty-nine thousand nine hundred and twenty-one antiretroviral-naive individuals starting
combination antiretroviral therapy from 1998 to 2006.
OUTCOME MEASURES
Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml
(virological response), CD4 increase of more than 100 cells/microl (immunological response)
and new AIDS/death were analysed using survival methods. Ten age strata were chosen: less
than 2, 2-5, 6-12, 13-17, 18-29, 30-39 (reference group), 40-49, 50-54, 55-59 and 60 years or
older; those aged 6 years or more were included in multivariable analyses.
RESULTS
The four youngest age groups had 223, 184, 219 and 201 individuals and the three oldest age
groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell
counts were highest in young children and declined with age. By 12 months, 53.7% (95%
confidence interval: 53.2-54.1%) and 59.2% (58.7-59.6%) had experienced a virological and
immunological response. The probability of virological response was lower in those aged 6-12
(adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24),
55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher
in children and younger adults and reduced in those 60 years or older. Those aged 55-59 and
60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count.
CONCLUSION
Better virological responses but poorer immunological responses in older individuals, together
with low precombination antiretroviral therapy CD4 cell counts, may place this group at
increased clinical risk. The poorer virological responses in children may increase the likelihood
of emergence of resistance.
48
BEH Numéro thématique n° 14-15, 2008, 98-101.
Transmission mère-enfant du VIH en France : l’impact majeur des stratégies
de prévention – Résultats de l’Enquête périnatale française ANRS-EPF.
Warszawski J, Tubiana R, Le Chenadec J, Teglas JP, Faye A, Dollfus C, Briand N,
Jasseron C, Rouzioux C, Blanche S, Mandelbrot L.
RESUME
En France, le taux de transmission du VIH-1 de la mère à l’enfant était de 17 % avant 1994, en
l’absence de prophylaxie antirétrovirale disponible. Il est passé à 1,6 % [IC 95 % : 1,3-2,0] entre
1997 et 2004, à l’ère des multithérapies puissantes et atteignait 0,4 % [0,1-0,9] lorsque la
charge virale proche de l’accouchement était inférieure à 50 cp/mL. Trois facteurs de risque
indépendants sont fortement liés à cette transmission « résiduelle » depuis 1997 : le terme
gestationnel à l’accouchement (risque 6 fois plus élevé pour les grands prématurés que pour
les enfants nés à terme), la charge virale en fin de grossesse (augmentation surtout importante
au-delà de 10 000 cp/mL), et la durée des antirétroviraux pendant la grossesse (antepartum).
Pour les 10 % de femmes en échec virologique à l’accouchement (>10 000 cp/mL), une
première consultation tardive en maternité et l’absence de perfusion per partum de zidovudine
sont associés à un risque accru de transmission. Dans la situation heureusement majoritaire
des femmes accouchant à terme avec une charge virale bien contrôlée (<400 cp/mL), le seul
facteur significativement associé au risque de transmission est la durée des antirétroviraux
administrés pendant la grossesse, le taux diminuant de manière linéaire avec l’augmentation de
cette durée.
ABSTRACT
In France, the rate of mother-to-child HIV1 transmission (MTCT) was 17% prior to 1994, due to
the absence of antiretroviral prophylaxis. It reached 1.6% (95% CI: 1.3-2.0) between 1997 and
2004, in the HAART era, and was as low as 0.4% (5/1338; 95% CI, 0.1-0.9) with maternal HIV-1
RNA level at delivery below 50 copies/mL. Three risk factors were independently associated
with residual transmission since 1997: gestational age (6 fold increase for severe premature
delivery compared with term births), viral load at delivery (10 times higher when viral load was
above rather than below 10,000 c/mL), and duration of antiretroviral therapy during pregnancy
(antepartum). In case of virological failure (>10 000 copies/mL), which concerned 10% of
mothers, late booking at maternity and lack of intrapartum zidovudine infusion were associated
with higher MTCT rate. In most case, mothers luckily delivered with well controlled viral load,
<400 copies/mL, and only duration of antenatal therapy was associated with transmission,
increasing duration being related with a linear decreasing transmission rate.
49
AIDS. 2008 Jan 11;22(2):289-99.
Mother-to-child HIV transmission despite antiretroviral therapy in the ANRS
French Perinatal Cohort.
Warszawski J, Tubiana R, Le Chenadec J, Blanche S, Teglas JP, Dollfus C, Faye A,
Burgard M, Rouzioux C, Mandelbrot L; ANRS French Perinatal Cohort.
OBJECTIVE
To identify factors associated with mother-to-child HIV-1 transmission (MTCT) from mothers
receiving antenatal antiretroviral therapy.
DESIGN
The French Perinatal Cohort (EPF), a multicenter prospective cohort of HIV-infected pregnant
women and their children.
METHODS
Univariate analysis and logistic regression, with child HIV status as dependent variable, were
conducted among 5271 mothers who received antiretroviral therapy during pregnancy,
delivered between 1997 and 2004 and did not breastfeed.
RESULTS
The MTCT rate was 1.3% [67/5271; 95% confidence interval (CI), 1.0-1.6]. It was as low as
0.4% (5/1338; 95% CI, 0.1-0.9) in term births with maternal HIV-1 RNA level at delivery below
50 copies/ml. MTCT increased with viral load, short duration of antiretroviral therapy, female
gender and severe premature delivery: 6.6% before 33 weeks versus 1.2% at 37 weeks or more
(P < 0.001). The type of antiretroviral therapy was not associated with transmission. Intrapartum
therapy was associated with four-fold lower MTCT (P = 0.04) in case of virological failure (> 10
000 copies/ml). Elective cesarean section tended to be inversely associated with MTCT in the
overall population, but not in mothers who delivered at term with viral load < 400 copies/ml
[odds ratio (OR), 0.83; 95% CI, 0.29-2.39; P = 0.37]. Among them, only duration of antenatal
therapy was associated with transmission (OR by week, 0.94; 95% CI, 0.90-0.99; P = 0.03).
CONCLUSIONS
Low maternal plasma viral load is the key factor for preventing MTCT. Benefits in terms of
MTCT reduction may be expected from early antiretroviral prophylaxis. The potential toxicity of
prolonged antiretroviral use in pregnancy should be evaluated.
50
Pediatr Infect Dis J. 2007 Oct;26(10):949-51.
Increased beta-2 microglobulinuria in human immunodeficiency virus-1infected children and adolescents treated with tenofovir.
Papaleo A, Warszawski J, Salomon R, Jullien V, Veber F, Dechaux M, Blanche S.
A single-center cross sectional evaluation of beta-2 micro-globinuria as a marker of proximal
renal tubule damage in 92 HIV-infected children showed that tenofovir treatment was
significantly associated with very high abnormal values. In view of the very long duration of
treatments for HIV infection, their possible consequences for the child's growing body should be
carefully evaluated.
51
Clin Infect Dis. 2007 Sep 15;45(6):785-94. Epub 2007 Aug 14.
Long-term non progression of HIV infection in children: evaluation of the
ANRS prospective French Pediatric Cohort.
Warszawski J, Lechenadec J, Faye A, Dollfus C, Firtion G, Meyer L, Douard D, Monpoux
F, Tricoire J, Benmebarek Y, Rouzioux C, Blanche S.
BACKGROUND
Some children who are infected with human immunodeficiency virus type 1 (HIV-1) during the
perinatal period remain asymptomatic for very long periods in the absence of antiretroviral
treatment, as is the case for some adults. Our objective was to estimate the proportion of
children who developed neither symptoms nor major immunological perturbations to the age of
> or = 10 years in a prospective cohort of infected children who had been observed since birth.
METHODS
The ongoing prospective French Pediatric Cohort includes 568 HIV-1-infected children. Here,
we report the follow-up data for all 348 HIV-1-infected children who were born before 1 January
1994. Children with long-term nonprogression of infection (LTNPs) were defined as HIV-1infected children who had been observed for at least 10 years, never received antiretroviral
treatment other than zidovudine monotherapy, never developed symptoms of Centers for
Disease Control and Prevention clinical category C or B, and had a CD4+ cell percentage of <
25% no more than once during follow-up. Other definitions were compared.
RESULTS
The Kaplan-Meier estimate of long-term nonprogression was 2.4% (95% confidence interval,
1.1%-4.6%) at 10 years of age, and 7 children were classified as LTNPs. The Kaplan-Meier
estimates decreased slightly with age, to 1.8% at 12 years of age and 1.4% at 14 years of age.
Plasma HIV-1 replication rates were low (< 1000 copies RNA/mL) for 2 of the 7 LTNPs at the
age of 10 years (0.6% of the total denominator). None of the routinely measured maternal or
perinatal markers were significantly linked to long-term nonprogression, with the exception of
the mother's Centers for Disease Control and Prevention clinical category at the time of
delivery.
CONCLUSIONS
Approximately 2% of children who were infected during the perinatal period displayed no
immunological or clinical progression by the age of 10 years. This figure is close to that reported
for adults in studies that have used similar definitions.
52
J Med Virol. 2007 Sep;79(9):1261-9.
Prevalence and risk factors associated with antiretroviral resistance in HIV1-infected children.
Delaugerre C, Warszawski J, Chaix ML, Veber F, Macassa E, Buseyne F, Rouzioux C,
Blanche S.
In the USA and West Europe, nearly 80% of HIV-1-infected adults, experiencing virologic
failure, harbored virus strain resistant to at least one antiretroviral drug. Limited data are
available on antiretroviral drug resistance in pediatric HIV infection. The aims of this study were
to analyze prevalence of HIV-1 drug resistance and to identify risk factors associated with
resistance in this population. Prevalence of genotypic resistance was estimated retrospectively
in treated children who experienced virologic failure (with HIV-1-RNA > 500 copies/ml) followed
in Necker hospital between 2001 and 2003. Among 119 children with resistance testing,
prevalence of resistance to any drug was 82.4%. Resistance ranged from 76.5% to nucleoside
reverse transcriptase inhibitor (NRTI), to 48.7% to non-nucleoside reverse transcriptase inhibitor
(NNRTI) and 42.9% to protease inhibitor (PI). Resistance to at least one drug of two classes
and three classes (triple resistance) was 31.9 and 26.9%, respectively. Resistance was not
associated with geographic origin, HIV-1 subtype, and CDC status. In multivariate analysis,
resistance to any drug remained associated independently with current low viral load and high
lifetime number of past PI. Triple resistance was independently associated with the high lifetime
number of past PI and with gender, particularly among children aged 11 years old or more with
a prevalence seven times higher in boys than in girls. In conclusion, antiretroviral resistance is
common among treated HIV-1-infected children and prevalence was similar with those
observed in adult population in the same year period. However, adolescent boys seem to be at
greater risk.
53
BMC Infect Dis. 2007 Jun 20;7:60.
Characteristics and management of HIV-1-infected pregnant women enrolled
in a randomised trial: differences between Europe and the USA.
Newell ML, Huang S, Fiore S, Thorne C, Mandelbrot L, Sullivan JL, Maupin R, Delke I,
Watts DH, Gelber RD, Cunningham CK; PACTG 316 Study Team.
BACKGROUND
Rates of mother-to-child transmission of HIV-1 (MTCT) have historically been lower in European
than in American cohort studies, possibly due to differences in population characteristics. The
Pediatric AIDS Clinical Trials Group Protocol (PACTG) 316 trial evaluated the effectiveness of
the addition of intrapartum/neonatal nevirapine in reducing MTCT in women already receiving
antiretroviral prophylaxis. Participation of large numbers of pregnant HIV-infected women from
the US and Western Europe enrolling in the same clinical trial provided the opportunity to
identify and explore differences in their characteristics and in the use of non-study interventions
to reduce MTCT.
METHODS
In this secondary analysis, 1350 women were categorized according to enrollment in centres in
the USA (n = 978) or in Europe (n = 372). Factors associated with receipt of highly active
antiretroviral therapy and with elective caesarean delivery were identified with logistic
regression.
RESULTS
In Europe, women enrolled were more likely to be white and those of black race were mainly
born in Sub-Saharan Africa. Women in the US were younger and more likely to have previous
pregnancies and miscarriages and a history of sexually transmitted infections.More than 90% of
women did not report symptoms of their HIV infection; however, more women from the US had
symptoms (8%), compared to women from Europe (4%). Women in the US were less likely to
have HIV RNA levels <400 copies/ml at delivery than women enrolling in Europe, and more
likely to receive highly active antiretroviral therapy, and to start therapy earlier in pregnancy.
The elective caesarean delivery rate in Europe was 61%, significantly higher than that in the US
(22%). Overall, 1.48% of infants were infected and there was no significant difference in the rate
of transmission between Europe and the US despite the different approaches to treatment and
delivery.
CONCLUSION
These findings confirm that there are important historical differences between the HIV-infected
pregnant populations in Western Europe and the USA, both in terms of the characteristics of the
women and their obstetric and therapeutic management. Although highly active antiretroviral
therapy predominates in pregnancy in both settings now, population differences are likely to
remain.
54
AIDS. 2007 May 11;21(8):993-1002.
Twin pregnancy as a risk factor for mother-to-child transmission of HIV-1:
trends over 20 years.
Scavalli Palladino C, Mandelbrot L, Berrebi A, Batallan A, Cravello L, Pannier E, Hamrene
K, Ciraru-Vigneron N, Faye A, Warszawski J; ANRS EPF.
OBJECTIVE
We investigated whether twin pregnancies were at increased risk of mother-to-child HIV-1
transmission (MTCT), in comparison with singletons.
METHODS
Among HIV-1 infected women enrolled in the French Perinatal HIV Cohort (n = 9262), we
studied the association between twin deliveries and MTCT rate according to three time periods
(pre-1994, 1994-1996, 1997-2004) and the effect of birth order. The mother was considered to
have transmitted if at least one of the twins was infected. Univariate and multivariate analyses
of risk factors for MTCT were performed for deliveries in the periods up to 1996.
RESULTS
Overall, 2.1% (192/9262) of all the deliveries were twins. The rate of prematurity was greater in
twins than in singletons (54% and 13%, respectively). Up to 1996 the rate of MTCT of HIV-1
was 28.3% (15/53) in twin pregnancies, versus 13.5% (414/3077) in singletons [odds ratio (OR),
2.5; 95% confidence interval (CI), 1.4-4.7; P = 0.002; adjusted OR, 2.3: 95% CI, 1.1-2.3; P =
0.03). In the period from 1997 to 2003, MTCT was low and did not differ between twins (1.0%)
and singletons (1.8%; P = 1.0). Overall, the transmission rate for the first-born child was
threefold that for the second-born child (14/164, 8.5% versus 4/164, 2.4%; P = 0.008).
CONCLUSION
Twin pregnancies were at increased risk of transmission, but in the era of HAART this risk was
reduced for twins, as well as singletons. Management of multiple pregnancies should take into
account the risks of premature rupture of the membranes and preterm delivery.
55
Environ Mol Mutagen. 2007 Apr-May;48(3-4):173-8.
Clinical mitochondrial dysfunction in uninfected children born to HIVinfected mothers following perinatal exposure to nucleoside analogues.
Benhammou V, Tardieu M, Warszawski J, Rustin P, Blanche S.
Clinical and biological observations of mitochondrial dysfunction in children exposed to
zidovudine (azidothymidine, AZT) during the perinatal period rapidly followed similar
observations in animal experiments. To date, two different disorders have been identified. The
first, asymptomatic hyperlactatemia, is observed during treatment in one third of exposed
newborns, and is reversible with treatment cessation. In rare cases, it is associated with
symptomatic acidosis. Regression may be slow, taking up to several months after the end of the
treatment. The long-term clinical consequences of this biochemical disturbance are unknown.
The second disorder involves severe neurological symptoms, which become clinically
detectable during the first 2 years of life. These symptoms are associated with a series of
biochemical and ultrastructural changes consistent with persistent mitochondrial dysfunction.
This latter phenomenon is rare, and affects only 0.3-0.5% of exposed children in the French
pediatric cohort, in which observations continue. Despite initial controversy, several similar
observations in other cohorts have since confirmed its occurrence. The pathophysiology of
these two mitochondrial dysfunctions may differ. Continued efforts to identify and understand
clinical mitochondrial toxicities are essential, given the intensification and diversification of
perinatal prophylaxis strategies, and the number of pregnant women potentially involved.
56
Arch Pediatr. 2007 Mar;14(3):298-302. Epub 2007 Feb 6.
HIV-1 drug resistance in French infected-children: from newborn to
adolescent
[Article in French]
Delaugerre C, Chaix ML, Warszawski J, Rouzioux C, Blanche S.
Limit of antiretroviral treatment success is the emergence of drug-resistant virus. As reported in
adult population, prevalence of resistance was high in treated HIV-infected children with
detectable HIV viral load. Resistance increased with number of prior antiretroviral treatments,
particularly with protease inhibitors. Adolescent boys seem at greater risk to harbor multiclasses resistant virus. In HIV-infected newborns, prevalence of resistance was 20%. Most of
resistance mutations detected were in accord to perinatal antiretroviral exposition. Principal
mechanism of resistance acquisition in newborns was transmission of resistant viruses from
mother to child with early archive in cellular reservoir and long term persistence with or without
treatment. Consequences of long term therapeutic strategies in children are major.
57
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