Four days/week antiretroviral maintenance strategy (ANRS 170 QUATUOR): substudies of reservoirs and ultrasensitive drug resistance
Author:
Lambert-Niclot Sidonie12ORCID, Abdi Basma13ORCID, Bellet Jonathan1, Fofana Djeneba12, De Truchis Pierre4, Amat Karine5, Alvarez Jean-Claude6ORCID, Surgers Laure17, Allavena Clothilde8, Zaegell-Faucher Olivia9, Morlat Philippe10, Palich Romain11ORCID, Gibowski Séverine12, Costagliola Dominique1ORCID, Girard Pierre-Marie7, Landman Roland13, Assoumou Lambert1, Morand-Joubert Laurence12, Lamaury Isabelle, Duvallon Emeline, Bani-Sadr Firouzé, Kmiec Isabelle, Force Gilles, Chabrol Amélie, Agher Nouara, Caby Fabienne, Wifaq Bouchra, Patey Olivier, Fresard Anne, Gagneux-Brunon Amandine, Chirouze Catherine, Duvivier Claudine, Lourenco Jérémie, Tolsma Violaine, Janssen Cécile, Lerolle Nathalie, Catalan Pilartxo, Rami Agathe, De Ponthaud Lucile, Pichancourt Gilles, Nasri Safa, Landowski Stéphanie, Marcou Morgane, Bottero Julie, Mfutila Kaykay Flory, Pialoux Gilles, Bouchaud Olivier, Abgrall Sophie, Gatey Caroline, Weiss Laurence, Pavie Juliette, Salmonceron Dominique, Zucman David, Fadli Amina, Lelievre Jean-Daniel, Palich Romain, Simon Anne, Beniken Dalila, Meyohas Marie-Caroline, Gras Julien, Cabie André, Pircher Mathilde, Morlat Philippe, Hessamfar Mojgam, Neau Didier, Cazenave Charles, Genet Claire, Faucher Jean-François, Makhloufi Djamila, Boibieux André, Bregigeon-Ronot Sylvie, Laroche Hélène, Sautereau Aurélie, Reynes Jacques, Makinson Alain, Raffi François, Bollengierstragier Olivier, Naqvi Alissa, Cua Eric, Rosenthal Eric, Breaud Sophie, Arvieux Cédrick, Vivent Jocelyne, Buzele Rodolphe, Rey David, Batard Marie-Laure, Bernard Louis, Delobel Pierre, Piffaut Marie, Verdon Renaud, Piroth Lionel, Blot Mathieu, Leclercq Pascale, Signori-Schmuck Anne, Huleux Thomas, Meybeck Agnès, May Thierry, Delestan Mickael, Miailhes Patrick, Perpoint Thomas, Greder-Belan Alix, Bornarel Dominique, Elharrar Brigitte, Khuong Marie-Aude, Poupard Marie, Blum Laurent, Michau Christophe, Grand Carole, Prazuck Thierry, Philibert Patrick, Gasse Barbara, Slama Laurence, Hikombo Hitoto, Darasteanu Iuliana, Itoua Françoise,
Affiliation:
1. Sorbonne Université, INSERM, Institut Pierre Louis d’Épidémiologie et de Santé Publique (IPLESP) , 184 rue du Faubourg Saint-Antoine, 75571 Cedex 12, Paris , France 2. AP-HP Hôpital Saint-Antoine, Laboratoire de Virologie , Paris , France 3. AP-HP Hôpital Pitié-Salpêtrière, Virology Department , Paris , France 4. Hôpitaux Universitaires Paris-Ile de France-Ouest, Hôpital Raymond Poincaré APHP, Université Versailles-Saint-Quentin, France, Infectious Diseases Department , Garches , France 5. Institut de Médecine et Epidémiologie Appliquée, Hôpital Bichat, Université Paris 7 , Paris , France 6. Département de Pharmacologie-Toxicologie, Hôpital R Poincaré APHP, Inserm U-1173, Université Versailles-Saint-Quentin , Garches , France 7. GHU APHP. Sorbonne Université, Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine , F75012, Paris , France 8. Hôpital Hôtel-Dieu, Infectious Diseases Department , Nantes , France 9. CHU Sainte-Marguerite, Assistance Publique Hôpitaux de Marseille, Infectious Diseases Department , Marseille , France 10. Hôpital Saint André, Internal Medicine and Infectious Diseases Department, CHU, Université de Bordeaux , Bordeaux , France 11. AP-HP Hôpital Pitié-Salpêtrière, Infectious Diseases Department , Paris , France 12. ANRS, MIE Maladies Infectieuses Emergentes , Paris , France 13. Infectious and Tropical Diseases Department, IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Bichat, AP-HP, Infectious and Tropical Diseases , Paris , France
Abstract
Abstract
Background
In a 4 days/week (4/7 days) maintenance strategy (ANRS-170 QUATUOR trial), the virological impact of an intermittent strategy was assessed by ultrasensitive virological analyses of reservoirs and resistance.
Methods
HIV-1 total DNA, ultra-sensitive plasma viral load (USpVL) and semen VL were measured in the first 121 participants. Sanger and ultra-deep sequencing (UDS) were performed on the HIV-1 genome (Illumina technology) according to the ANRS consensus. A generalized estimation equation with a Poisson distribution was used to compare changes in the proportion of residual viraemia, detectable semen HIV RNA and HIV DNA within and between the two groups over time.
Results
The proportion of participants with residual viraemia at Day 0 (D0) and Week 48 (W48) was 16.7% and 25.0% in the 4/7 days group and 22.4% and 29.7% in the 7/7 days group, respectively (+8.3% versus +7.3%, P = 0.971). The proportion of detectable DNA (>40 copies/106 cells) at D0 and W48 was 53.7% and 57.4% in the 4/7 days group and 56.1% and 51.8% in the 7/7 days group, respectively (+3.7% versus −4.3%, P = 0.358). Semen HIV RNA was detectable (≥100 copies/mL) in 2.2% of participants at D0 and 4.5% at W48 in the 4/7 days group versus 6.1% and 9.1% in the 7/7 days group, respectively (+2.3% versus +3.0%, P = 0.743). Emerging resistance at failure was more frequent in the 4/7 days group detected by Sanger sequencing: 3/6 participants versus 1/4 in the 7/7 days group, and similar with the UDS assay: 5/6 versus 4/4, respectively.
Conclusions
These findings support the potency of a 4/7 days maintenance strategy on virological suppression at the reservoirs and emergent resistance level, including minority variants.
Funder
ANRS Emerging Infectious Diseases
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)
Cited by
3 articles.
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