Yves Lévy, MD, PhD *; Jean-Daniel Lelièvre, MD, PhD* *; Lambert Assoumou, PhD; Esther Aznar, MD; Federico Pulido, PhD; Giuseppe Tambussi, MD; Manuel Crespo, PhD; Agnès Meybeck, MD; Jean-Michel Molina, MD, PhD; Constance Delaugerre, MD, PhD; Jacques Izopet, MD, PhD; Gilles Peytavin, PhD; Fanny Cardon, MSc; Alpha Diallo, MD, MPH; Rémi Lancar, PhD; Lydie Béniguel, PhD; Dominique Costagliola, PhD
Note: All authors contributed to interpretation of the data, revised the manuscript critically, and approved the final version.
Acknowledgment: The authors thank the ANRS 146 – GeSIDA 7211 OPTIMAL study participants and all site collaborators for their contributions to the conduct of the trial (see the Appendix).
Financial Support: By INSERM-ANRS (French National Agency for Research on AIDS) and ViiV Healthcare.
Disclosures: Dr. Lelièvre reports personal fees from Gilead and grants from Janssen outside the submitted work. Dr. Pulido reports grants from Fundación SEIMC-GeSIDA during the conduct of the study and personal fees and nonfinancial support from Gilead; grants, personal fees, and nonfinancial support from Janssen; personal fees from MSD; and personal fees and nonfinancial support from ViiV Healthcare outside the submitted work. Dr. Meybeck reports personal fees and nonfinancial support from Gilead, Janssen, and ViiV Healthcare outside the submitted work. Dr. Molina reports grants from Gilead Sciences and personal fees from Gilead Sciences, Merck, and ViiV Healthcare outside the submitted work. Dr. Delaugerre reports personal fees from ViiV Healthcare, Gilead, and MSD and grants from ViiV Healthcare outside the submitted work. Dr. Peytavin reports grants from Gilead Sciences, ViiV Healthcare, and Merck and personal fees from Gilead Sciences, ViiV Healthcare, Janssen, and Merck outside the submitted work. Dr. Costagliola reports grants and personal fees from Janssen, personal fees from Merck Switzerland, grants and personal fees from MSD France, and personal fees from Gilead outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-2133.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Data Sharing Statement: The authors have indicated that they will not be sharing data.
Corresponding Authors: Yves Lévy, MD, PhD, and Jean-Daniel Lelièvre, MD, PhD, Clinical Immunology and Infectious Diseases Department, Henri Mondor Hospital, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France; e-mail, firstname.lastname@example.org and email@example.com.
Current Author Addresses: Drs. Lévy and Lelièvre: Clinical Immunology and Infectious Diseases Department, Henri Mondor Hospital, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France.
Drs. Assoumou, Lancar, Béniguel, and Costagliola: INSERM, Sorbonne Université, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP), 56 Bd Vincent Auriol, 75013 Paris, France.
Dr. Aznar: FUNDACION SEIMC-GESIDA (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica - Grupo de Estudio del SIDA), C/ Modeguera, 29, 17248 S'Agaro, Girona, Spain.
Dr. Pulido: Centro de Actividades Ambulatorias, Hospital 12 de Octubre, 2a planta D, consulta 10, 28041 Madrid, Spain.
Dr. Tambussi: IRCCS (Istituto di ricovero e cura a carattere scientifico)-Ospedale San Raffaele, Via Stamira d'Ancona 20, 20127 Milano, Italy.
Dr. Crespo: Infectious Disease Unit, Internal Medicine Department, Hospital Alvaro Cunqueiro, Estrada Clara Campoamor no 341, 36216 Vigo, Pontevedra, Spain.
Dr. Meybeck: Service Universitaire des Maladies Infectieuses et du Voyageur, Centre Hospitalier de Tourcoing, 135 avenue du Président Coty, 59 Tourcoing, France.
Drs. Molina and Delaugerre: INSERM U944, Université de Paris, Hôpital Saint-Louis, APHP, 1 avenue Claude Vellefaux, 75010 Paris, France.
Dr. Izopet: INSERM, U1043, Université Toulouse III Paul-Sabatier, Faculté de Médecine Toulouse-Purpan, 330 avenue de Grande-Bretagne - TSA 4003, 31059 Toulouse, France.
Dr. Peytavin: Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pharmacologie-Toxicologie, Hôpital Bichat-Claude Bernard, APHP, 46 rue Henri Huchard, 75018 Paris, France.
Ms. Cardon and Dr. Diallo: ANRS, France Recherche Nord & Sud Sida-HIV Hépatites, Agence autonome de l'INSERM, 101 rue de Tolbiac, 75013 Paris, France.
Author Contributions: Conception and design: Y. Lévy, J. Lelièvre, L. Assoumou, E. Aznar, F. Pulido, C. Delaugerre, D. Costagliola.
Analysis and interpretation of the data: Y. Lévy, J. Lelièvre, L. Assoumou, F. Pulido, G. Tambussi, J. Molina, C. Delaugerre, J. Izopet, G. Peytavin, A. Diallo, D. Costagliola.
Drafting of the article: Y. Lévy, J. Lelièvre, L. Assoumou, C. Delaugerre, G. Peytavin, D. Costagliola.
Critical revision of the article for important intellectual content: J. Lelièvre, F. Pulido, G. Tambussi, M. Crespo, J. Molina, G. Peytavin, D. Costagliola.
Final approval of the article: Y. Lévy, J. Lelièvre, L. Assoumou, E. Aznar, F. Pulido, G. Tambussi, M. Crespo, A. Meybeck, J. Molina, C. Delaugerre, J. Izopet, G. Peytavin, F. Cardon, A. Diallo, R. Lancar, L. Béniguel, D. Costagliola.
Provision of study materials or patients: Y. Lévy, J. Lelièvre, F. Pulido, G. Tambussi, M. Crespo, J. Molina, J. Izopet, L. Béniguel.
Statistical expertise: L. Assoumou, R. Lancar, D. Costagliola.
Obtaining of funding: Y. Lévy, J. Lelièvre, D. Costagliola.
Administrative, technical, or logistic support: E. Aznar, J. Izopet, G. Peytavin, F. Cardon, A. Diallo, L. Béniguel.
Collection and assembly of data: J. Lelièvre, L. Assoumou, E. Aznar, F. Pulido, A. Meybeck, C. Delaugerre, A. Diallo, L. Béniguel, D. Costagliola.
Patients diagnosed with advanced HIV infection have a poor prognosis despite initiation of combined antiretroviral therapy (c-ART).
To assess the benefit of adding maraviroc, an antiretroviral drug with immunologic effects, to standard c-ART for patients with advanced disease at HIV diagnosis.
Randomized controlled trial. (ClinicalTrials.gov: NCT01348308)
Clinical sites in France (n = 25), Italy (n = 5), and Spain (n = 20).
416 HIV-positive, antiretroviral-naive adults with CD4 counts less than 0.200 × 109 cells/L and/or a previous AIDS-defining event (ADE).
C-ART plus placebo or maraviroc (300 mg twice daily with dose modification) for 72 weeks.
The primary end point was first occurrence of severe morbidity (new ADE, selected serious infections, serious non-ADE, immune reconstitution inflammatory syndrome, or death). Prespecified secondary outcomes included primary outcome components, biological and pharmacokinetic measures, and adverse events graded 2 or higher.
409 randomly assigned participants (207 in the placebo group and 202 in the maraviroc group) who received more than 1 dose were included in the analysis. During 72 weeks of follow-up, incidence of severe morbidity was 11.1 per 100 person-years in the maraviroc group and 11.2 per 100 person-years in the placebo group (hazard ratio, 0.97 [95% CI, 0.57 to 1.67]). Incidence of adverse events graded 2 or higher was 36.1 versus 41.5 per 100 person-years (incidence rate ratio, 0.87 [CI, 0.65 to 1.15]).
Sixty-four participants discontinued therapy during follow-up. The study was not designed to evaluate time-dependent outcomes or effect modification.
Addition of maraviroc to standard c-ART does not improve clinical outcomes of patients initiating therapy for advanced HIV infection.
INSERM-ANRS (French National Agency for Research on AIDS).
Lévy Y, Lelièvre J, Assoumou L, et al. Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection: A Randomized Trial. Ann Intern Med. 2020;:. [Epub ahead of print 11 February 2020]. doi: https://doi.org/10.7326/M19-2133
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Published: Ann Intern Med. 2020.
HIV, Infectious Disease.
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