title: Intensive five-drug antiretroviral therapy regimen versus standard triple-drug therapy during primary HIV-1 infection (OPTIPRIM-ANRS 147): a randomised, open-label, phase 3 trial.
abstract: BACKGROUND
  Early combination antiretroviral therapy (cART) initiation at the time of primary HIV-1 infection could restrict the establishment of HIV reservoirs. We aimed to assess the effect of a cART regimen intensified with raltegravir and maraviroc, compared with standard triple-drug cART, on HIV-DNA load.
  
  
  METHODS
  In this randomised, open-label, phase 3 trial, we recruited patients from hospitals across France. Inclusion criteria were primary HIV-1 infection (an incomplete HIV-1 western blot and detectable plasma HIV-RNA), with either symptoms or a CD4+ cell count below 500 cells per μL. Patients were randomly assigned (1:1) to an intensive, five-drug cART regimen (raltegravir 400 mg and maraviroc 150 mg twice daily, and a fixed-dose combination of tenofovir disoproxil fumarate 300 g plus emtricitabine 200 g, darunavir 800 g, and ritonavir 100 g once daily) or a standard triple-drug cART regimen (tenofovir disoproxil fumarate 300 g plus emtricitabine 200 g, darunavir 800 g, and ritonavir 100 g once daily) using a predefined randomised list generated by randomly selected variable block sizes. The primary endpoint was the median number of HIV-DNA copies per 10(6) peripheral blood mononuclear cells (PBMC) at month 24, analysed in the modified intention-to-treat population, defined as all patients who started their assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01033760.
  
  
  RESULTS
  Between April 26, 2010, and July 13, 2011, 110 patients were enrolled, of whom 92 were randomly assigned and 90 started treatment (45 in each treatment group). Six (13%) patients in the intensive cART group and two (4%) in the standard cART group discontinued before month 24. At month 24, HIV-DNA loads were similar between groups (2·35 [IQR 2·05-2·50] log₁₀ per 10(6) PBMC in the intensive cART group vs 2·25 [1·71-2·55] in the standard cART group; p=0·21). Eight grade 3-4 clinical adverse events were reported in seven patients in the intensive cART group and seven grade 3-4 clinical adverse events were reported in seven patients in the standard cART group. Three serious clinical adverse events occurred: two (pancreatitis and lipodystrophy) in the standard cART group, which were regarded as treatment related, and one event (suicide attempt) in the intensive cART group that was unrelated to treatment.
  
  
  CONCLUSIONS
  After 24 months, cART intensified with raltegravir and maraviroc did not have a greater effect on HIV blood reservoirs than did standard cART. These results should help to design future trials of treatments aiming to decrease the HIV reservoir in patients with primary HIV-1 infection.
  
  
  BACKGROUND
  Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck, and ViiV Laboratories.
authors.affiliation: EA 7327, Paris Descartes University - Sorbonne Paris Cité, Paris, France; Infectious Diseases Department, Tourcoing Hospital, Tourcoing, France; Internal Medicine Department, AP-HP, Bicêtre Hospital, Le Kremlin-Bicêtre, France. Electronic address: antoinecheret@free.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Chéret
authors.affiliation: INSERM U1018, Faculty of Medicine, Paris-Sud University, AP-HP, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Nembot
authors.affiliation: EA 7327, Paris Descartes University - Sorbonne Paris Cité, Paris, France; Virology Laboratory, AP-HP, Necker Hospital, Paris, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Mélard
authors.affiliation: Infectious Diseases Department, AP-HP, Saint-Louis Hospital, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lascoux
authors.affiliation: Infectious Diseases Department, AP-HP, Tenon Hospital, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Slama
authors.affiliation: Infectious Diseases Department, Croix Rousse Hospital, Lyon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Miailhes
authors.affiliation: Infectious Diseases Department, AP-HP, Bichat Claude-Bernard Hospital, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Yeni
authors.affiliation: Infectious Diseases Department, CHU de Fort de France, Martinique, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Abel
authors.affiliation: EA 7327, Paris Descartes University - Sorbonne Paris Cité, Paris, France; Virology Laboratory, AP-HP, Necker Hospital, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Avettand-Fenoel
authors.affiliation: INSERM U1012, Faculty of Medicine, Paris-Sud University, AP-HP, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Venet
authors.affiliation: EA 7327, Paris Descartes University - Sorbonne Paris Cité, Paris, France; Virology Laboratory, AP-HP, Necker Hospital, Paris, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.affiliation: Infectious Diseases Department, AP-HP, Saint-Louis Hospital, Paris, France; INSERM U941, University of Paris Diderot, Paris, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.affiliation: Infectious Diseases Department, AP-HP, La Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.affiliation: Internal Medicine Department, AP-HP, Bicêtre Hospital, Le Kremlin-Bicêtre, France; INSERM U1018, Faculty of Medicine, Paris-Sud University, AP-HP, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.affiliation: Virology Laboratory, AP-HM, La Timone Hospital, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Tamalet
authors.affiliation: Collège des Universitaires des Maladies Infectieuses et Tropicales (CMIT), Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.affiliation: Infectious Diseases Department, Font-Pré Hospital, Toulon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lafeuillade
authors.affiliation: Infectious Diseases Department, Gui de Chauliac Hospital, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.affiliation: Infectious Diseases Department, AP-HM, La Timone Hospital, Marseille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ravaux
authors.affiliation: Infectious Diseases Department, CHU Ricou Hospital, Pointe à Pître, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Hoën
authors.affiliation: Internal Medicine Department, AP-HP, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.affiliation: INSERM U1018, Faculty of Medicine, Paris-Sud University, AP-HP, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.affiliation: EA 7327, Paris Descartes University - Sorbonne Paris Cité, Paris, France; Virology Laboratory, AP-HP, Necker Hospital, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D005260:Female; D005602:France; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents