title: Efficacy and safety of once-daily ritonavir-boosted atazanavir or darunavir in combination with a dual nucleos(t)ide analogue backbone in HIV-1-infected combined ART (cART)-naive patients with severe immunosuppression: a 48 week, non-comparative, randomized, multicentre trial (IMEA 040 DATA trial).
abstract: Boosted PIs are commonly prescribed in patients presenting with advanced HIV infection. We assessed the efficacy and tolerability of once-daily ritonavir-boosted atazanavir or darunavir plus two NRTIs in HIV-1-infected ART-naive patients with severe immunosuppression, targeting at least an 85% success rate at week 48.
  
  
  
  This 48 week, open-label, non-comparative, randomized, multicentre trial included ART-naive patients with CD4 cell counts <200 cells/mm(3), with plasma HIV-1 RNA >1000 copies/mL and without genotypic mutations conferring resistance to the study drugs. Patients were randomized (1:1) to receive once-daily atazanavir/ritonavir (300/100 mg) or darunavir/ritonavir (800/100 mg) plus tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine. The primary endpoint was treatment success, defined as plasma HIV-1 RNA ≤50 copies/mL at week 48 and no permanent PI/ritonavir discontinuation. The study was registered with ClinicalTrials.gov (NCT01928407).
  
  
  
  One hundred and twenty patients were enrolled: 77% were men, 30% were born in Africa and 39% had AIDS. The median baseline CD4 and plasma HIV-RNA values were 69 cells/mm(3) and 5.4 log10 copies/mL. All but four patients received tenofovir disoproxil fumarate/emtricitabine. The week 48 treatment success rate was 66% (95% CI 54%-78%) with atazanavir/ritonavir and 80% (95% CI 68%-89%) with darunavir/ritonavir. The median CD4 cell count increased similarly in the two groups (Δweek 48 to week 0: +194 cells/mm(3)). Adverse events occurred in 23 and 18 patients, respectively.
  
  
  
  Despite good adherence, neither study regimen reached the predefined objective, suggesting a need for more potent regimens for patients with advanced HIV infection.
authors.affiliation: Tenon APHP, Maladies Infectieuses, F-75020, Paris, France laurence.slama@aphp.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Slama
authors.affiliation: Bichat Claude Bernard, APHP, Maladies Infectieuses, F-75018 Paris, France Institut de Médecine et d'Epidémiologie Appliquées, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018, Paris, France Institut de Médecine et d'Epidémiologie Appliquées, UMR 1137, Inserm, F-75018, Paris, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Landman
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France.
authors.forename: Lambert
authors.initials: L
authors.lastname: Assoumou
authors.affiliation: Institut de Médecine et d'Epidémiologie Appliquées, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018, Paris, France.
authors.forename: Aida
authors.initials: A
authors.lastname: Benalycherif
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, U1135, CIMI, F-75013, Paris, France.
authors.forename: Assia
authors.initials: A
authors.lastname: Samri
authors.affiliation: Bichat Claude Bernard, APHP, Maladies Infectieuses, F-75018 Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Joly
authors.affiliation: Tenon APHP, Maladies Infectieuses, F-75020, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Pialoux
authors.affiliation: Saint Antoine APHP, Maladies Infectieuses, F-75012 Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Valin
authors.affiliation: Fort de France, Maladies Infectieuses, Martinique, France.
authors.forename: André
authors.initials: A
authors.lastname: Cabié
authors.affiliation: Necker Enfants malades, APHP, Maladies Infectieuses, Centre d'infectiologie Necker-Pasteur, Paris, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Duvivier
authors.affiliation: APHP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris F-75013, France.
authors.forename: Sidonie
authors.initials: S
authors.lastname: Lambert-Niclot
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France APHP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris F-75013, France.
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: IAME, UMR 1137, INSERM et Université Paris Diderot, Sorbonne Paris Cité et AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Pharmaco-Toxicologie, F-75018 Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.affiliation: Institut de Médecine et d'Epidémiologie Appliquées, UMR 1137, Inserm, F-75018, Paris, France Saint Antoine APHP, Maladies Infectieuses, F-75012 Paris, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
mesh_terms: D000328:Adult; D000349:Africa; D000368:Aged; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D000069446:Atazanavir Sulfate / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D000069454:Darunavir / Q000009:adverse effects / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D009705:Nucleosides; D000069446:Atazanavir Sulfate; D019438:Ritonavir; D000069454:Darunavir