Does transient cART started during primary HIV infection undermine the long-term immunologic and virologic response on cART resumption?

Evguenia Krastinova; Remonie Seng; Jerome Lechenadec; Henri Panjo; Asma Essat; Djamila Makhloufi; Martine Obadia; Louis Bernard; Cecile Goujard; Laurence Meyer; ANRS PRIMO cohort

doi:10.1186/s12879-015-0892-1

Does transient cART started during primary HIV infection undermine the long-term immunologic and virologic response on cART resumption?

BMC Infect Dis. 2015 Apr 10:15:178. doi: 10.1186/s12879-015-0892-1.

Authors

Evguenia Krastinova^{1

2}, Remonie Seng^{3

4}, Jerome Lechenadec⁵, Henri Panjo⁶, Asma Essat⁷, Djamila Makhloufi⁸, Martine Obadia⁹, Louis Bernard¹⁰, Cecile Goujard^{11

12}, Laurence Meyer^{13

14}; ANRS PRIMO cohort

Collaborators

ANRS PRIMO cohort:
Thierry Allegre, Jean-Michel Livrozet, François Jeanblanc, Pierre Chiarello, Djamila Makhloufi, Dominique Peyramond, Patrick Miailhes, Joseph Koffi, Thomas Baudry, Sylvie Pailhes, Julie Allemand, Edith Danielli, Gisèle Philip, Gilles Hittinger, Assi Assi, Alain Rieu, Véronique Lambry, Jean-Gabriel Fuzibet, Jill-Patrice Cassuto, Pierre Dellamonica, Anne Leplatois, Alissa Naqvi, Pierre Marie Roger, Pascal Pujliese, Jacques Durant, Eric Cua, Matteo Vassallo, Isabelle Ravaux, Isabelle Poizot Martin, Gilles Pichancourt, Henri Duffaut, Philippe Morlat, Fabrice Bonnet, Isabelle Louis, Caroline Aslan, Denis Malvy, Denis Lacoste, Mojgan Bonarek, Mojgan Marie-Anne Vandenhende, Jean Delaun, Sabrina Caltado, Jean-Marie Ragnaud, Michel Dupont, Hervé Dutronc, Charles Cazenave, Didier Neau, Thierry Pistone, Elodie Blanchard, Laetitia Lacaze-Buz, Jean-Luc Pellegrin, Isabelle Raymond, Carine Greib, Gaetane Wirth, Francis Saint Dizier, Daniel Garipuy, Martine Obadia, Marie Chauveau, Jacques Reynes, Vincent Baillat, Corinne Merle, Vincent Lemoing, Nadine Atoui, Alain Makinson, Jean Marc Jacquet, Christina Psomas, Antoine Villadero, Christine Tramoni, Hugues Aumaitre, Mathieu Saada, Marie Medus, Martine Malet, Ségolène Neuville, Milagros Ferreyra, André Cabie, Sylvie Abel, Guillaume Hurtrel, Patrick Hochedez, Guillaume Avenin, Nicolas Vignier, Bernard Liautaud, Christelle Baringthon, Catherine Michel, Jean-Michel Peter, Charles Beck, Jean-Michel Halna, Meryem Benomar, Bruno Hoen, Christine Drobacheff-Thiebaut, Jean-François Faucher, Adeline Foltzer, François Parcelier, Catherine Bourdeaux, Lionel Piroth, Thierry May, Laurence Boyer, Simone Wassoumbou, Masha Mohseni Zadeh, Martin Martinot, Anne Pachart, David Rey, Maria Partisani, Christine Cheneau, Michèle Priester, Claudine Bernard-Henry, Erick De Mautort, Patricia Fischer, Thomas Huleux, Isabelle Alcaraz, Christophe Allienne, Antoine Cheret, Xavier de la Tribonniere, Hugues Melliez, Agnès Meybeck, Bertrand Riff, Michel Valette, Nathalie Viget, Emmanuelle Aissi, Dominique Merrien, Gilles Blaison, Mahsa Mohseni Zadeh, Martin Martinot, Anne Pachart, François Raffi, Clotilde Allavena, Jean-Philippe Talarmin, Olivier Mounoury, Eric Billaud, Cecile Brunet, Sabelline Bouchez, Nicolas Feuillebois, David Boutoille, Delphine Brosseau, Christian Michelet, Pierre Tattevin, Matthieu Revest, Helene Leroy, Jean-Marc Chapplain, Fabien Fily, Maja Rasjtajack, Anne Martin, Philippe Feret, Claude Beuscart, Corinne Daniel, Sylvie Le Moal, Elizabeth Duhamel, Anne Gatel, Elisabeth Pape, Pascale Fialaire, Jean Marie Chennebault, Valérie Rabier, Pierre Abgueguen, Odile Luycx, Mathilde Niault, Philippe Moreau, Yves Poinsignon, Anabèle dos Santos, Virginie Mouton-Rioux, Dominique Houlbert, Frédérique Barbe, Philippe Perre, Sophie Leantez-Nainville, Thomas Guimard, Jean-Jacques Girard, Véronique Simonet, C H U Charles Nicolle de Rouen, Christine Jacomet, Claire Genet, Bruno Abraham, Alain Regnier, Odile Antoniotti, Jean-Michel Molina, Samuel Ferret, Nathalie Colin De Verdiere, Diane Ponscarme, Nathalie De Castro, Alexandre Aslan, Willy Rozenbaum, Jerome Goguel, Claire Pintado, Sebastien Gallien, François Clavel, Caroline Gatey, Caroline Lascoux-Combe, Olivier Taullera, Claire Pintado, Jeannine Delgado, Julie Timsit, Laurence Gerard, Pierre-Marie Girard, Odile Picard, Diane Bollens, Nadia Valin, Pauline Campa, Patrick Yeni, Bao Phung, Bilguissa Diallo, Catherine Leport, Corinne Jadand, Gilles Pialoux, Thomas Lyavanc, Laurence Slama, Aurélie Durel, Agathe Rami, Maguy Parrinello, Dominique Salmon, Catherine Chakvetadze, Linda Belarbi, Odile Launay, Benjamin Silbermann, Marie-Pierre Pietri, G H Cochin, Anne Simon, Manuela Bonmarchand, François Pichon, Jean-Luc Vourch, Michele Pauchard, G H Pitié-Salpétrière, Christine Katlama, Marc Antoine Valantin, Fabienne Caby, Luminita Schneider, Sophie Seang, Saadia Ben Abdallah, G H Pitié-Salpétrière, Laurence Weiss, Martin Buisson, Jean-Paul Viard, Jacques Gilquin, Alain Sobel, Blanka Hadacek, Olivier Zak-Dit-Zbar, Paul Henri Consigny, Claudine Duvivier, Fatima Touam, Isabelle Sauret, Sylvie Gibert, Jade Ghosn, Yann Quertainmont, Martin Duracinsky, Olivier Segeral, Arnaud Blanc, Delphine Peretti, Valerie Seguin, Marie josée Dulucq, Yves Levy, Anne Sophie, Jean Daniel Lelievre, Cécile Dumont, Renato Fior, Pierre De Truchis, Huguette Berthe, Pierre Chevojon, Pierre Chevojon, Alain Devidas, Olivier Patey, Isabelle Turpault, Yvon Lemercier, Fabrice Chaix, Olivier Bouchaud, Sophie Abgrall, Regine Barruet, Frederic Mechai, Patricia Honore, Elisabeth Rouveix, Evelyne Reimann, Alix Greder Belan, Claire Godin Collet, Maria Ruquet, C H Andre Mignot, Isabelle Mahe, Emmanuel Mortier, Martine Bloch, Anne-Marie Simonpoli, Isabelle Cahitte, Benedicte Montoya, David Zucman, Catherine Majerholc, Dominique Bornarel, Justine Gellen-Dautremer, A Tadlaoui, Vincent Daneluzzi, Juliette Gerbe, Olivier Patey, Bantsimba Jonas, Sophie Delllion, Pauline Caraux Paz, Benoit Cazenave, Laurent Richier, Isabelle Delacroix, Brigitte Elharrar, Laurent Richier, Médecine Interne, Daniel Vittecoq, Lelia Escaut, Claudine Bolliot, Annie Lepretre, Philippe Genet, Juliette Gerbe, Véronique Perrone, François Quesnay, Jean-Luc Boussard, Patricia Chardon, Marc Jacquet, Eric Froguel, Sylvie Tassie

Affiliations

¹ INSERM, U1018, Epidemiology of HIV and STI, CESP; University Paris-Sud, Le Kremlin-Bicêtre, France. [email protected].
² Department of Public Health and Epidemiology, Bicêtre Hospital, AP-HP, Le Kremlin Bicêtre, France. [email protected].
³ INSERM, U1018, Epidemiology of HIV and STI, CESP; University Paris-Sud, Le Kremlin-Bicêtre, France. [email protected].
⁴ Department of Public Health and Epidemiology, Bicêtre Hospital, AP-HP, Le Kremlin Bicêtre, France. [email protected].
⁵ INSERM, U1018, Epidemiology of HIV and STI, CESP; University Paris-Sud, Le Kremlin-Bicêtre, France. [email protected].
⁶ INSERM, U1018, Gender, Sexual and Reproductive Health, Le Kremlin-Bicêtre, France. [email protected].
⁷ INSERM, U1018, Epidemiology of HIV and STI, CESP; University Paris-Sud, Le Kremlin-Bicêtre, France. [email protected].
⁸ Department of Infectious and Tropical Disease, Edouard Herriot Hospital, Lyon, France. [email protected].
⁹ Department of Infectious and Tropical Disease, Purpan Hospital, Toulouse, France. [email protected].
¹⁰ Department of Infectious and Tropical Disease, Bretonneau Hospital, Tours, France. [email protected].
¹¹ INSERM, U1018, Epidemiology of HIV and STI, CESP; University Paris-Sud, Le Kremlin-Bicêtre, France. [email protected].
¹² Department of Internal Medicine, Bicêtre Hospital, AP-HP; University Paris-Sud, Le Kremlin-Bicêtre, France. [email protected].
¹³ INSERM, U1018, Epidemiology of HIV and STI, CESP; University Paris-Sud, Le Kremlin-Bicêtre, France. [email protected].
¹⁴ Department of Public Health and Epidemiology, Bicêtre Hospital, AP-HP, Le Kremlin Bicêtre, France. [email protected].

Abstract

Background: We explored the impact of transient cART started during the primary HIV-infection (PHI) on the long-term immunologic and virologic response on cART resumption, by comparison with treatment initiation during the chronic phase of HIV infection (CHI).

Methods: We analyzed data on 1450 patients enrolled during PHI in the ANRS PRIMO cohort between 1996 and 2013. "Treatment resumption" was defined as at least 3 months of resumed treatment following interruption of at least 1 month of treatment initiated during PHI. "Treatment initiation during CHI" was defined as cART initiated ≥6 months after PHI. The virologic response to resumed treatment and to treatment initiated during CHI was analyzed with survival models. The CD4 cell count dynamics was modeled with piecewise linear mixed models.

Results: 136 patients who resumed cART for a median (IQR) of 32 (18-51) months were compared with 377 patients who started cART during CHI for a median of 45 (22-57) months. Most patients (97%) achieved HIV-RNA <50 cp/mL after similar times in the two groups. The CD4 cell count rose similarly in the two groups during the first 12 months. However, after 12 months, patients who started cART during CHI had a better immunological response than those who resumed cART (p = 0.01); therefore, at 36 months, the gains in √CD4 cells/mm(3) and CD4% were significantly greater in patients who started treatment during CHI.

Conclusion: These results suggest that interruption of cART started during PHI has a significant, albeit modest negative impact on CD4 cell recovery on cART resumption.

MeSH terms

Adult
Anti-HIV Agents / therapeutic use
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes / cytology
CD4-Positive T-Lymphocytes / immunology
Cohort Studies
Female
HIV / genetics*
HIV Infections / diagnosis*
HIV Infections / drug therapy
HIV Infections / virology
Humans
Male
Middle Aged
RNA, Viral / analysis

Substances

Anti-HIV Agents
RNA, Viral