title: Cyclosporine A in addition to standard ART during primary HIV-1 infection: pilot randomized clinical trial.
abstract: Initiating ART during acute/recent HIV-1 infection reduces viral reservoir formation. It has been proposed that, during this phase, the size of the viral reservoir could be further reduced by the association of immunomodulatory therapy with ART. Contradictory results have emerged, however, from two trials evaluating the impact on immune recovery and the viral reservoir of adding cyclosporine A to ART during primary HIV-1 infection.
  
  
  
  Twenty patients with acute/recent HIV-1 infection were randomized to receive ART alone (tenofovir, emtricitabine and lopinavir/ritonavir) or associated with 8 weeks of cyclosporine A (0.3-0.6 mg/kg twice daily). The impact on viral load, immune response and integrated and non-integrated DNA viral reservoir at 0, 8 and 36 weeks of treatment was evaluated.
  
  
  
  The estimated median time from HIV-1 infection to ART onset was 63 days (IQR 53; 79.5) with 90% of patients at Fiebig V stage. No significant differences were observed in viral load decay, CD4 T cell recovery, immune response markers or the evolution of integrated DNA at week 8 (end of cyclosporine A) and week 36 between groups. However, non-integrated DNA significantly increased in the cyclosporine A arm between weeks 0 and 36. Cyclosporine A was well tolerated.
  
  
  
  Adding cyclosporine A to ART during acute/recent infection did not improve immune recovery. However, unintegrated DNA increased in the cyclosporine A group, suggesting an anti-integration effect, a point warranting further research (ClinicalTrials.gov Identifier: NCT00979706).
authors.affiliation: Infectious Diseases Service, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Nicolás
authors.affiliation: Infectious Diseases Service, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Ambrosioni
authors.affiliation: Infectious Diseases Service, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Omar
authors.initials: O
authors.lastname: Sued
authors.affiliation: Pharmacology and Toxicology Department, Biomedical Diagnostic Center, Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Mercé
authors.initials: M
authors.lastname: Brunet
authors.affiliation: Infectious Diseases Service, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: López-Diéguez
authors.affiliation: Infectious Diseases Service, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Manzardo
authors.affiliation: Infectious Diseases Service, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Agüero
authors.affiliation: Pharmacy Department, Hospital Clinic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Tuset
authors.affiliation: Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.affiliation: Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Alberto C
authors.initials: AC
authors.lastname: Guardo
authors.affiliation: Department of Clinical Microbiology, Hospital Clínic, Barcelona, Spain/ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: María Mar
authors.initials: MM
authors.lastname: Mosquera
authors.affiliation: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Spanish HIV-HGM Biobank, Networking Research Center on Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.affiliation: Otorhinolaryngology Department, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Caballero
authors.affiliation: Department of Clinical Microbiology, Hospital Clínic, Barcelona, Spain/ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Marcos
authors.affiliation: Infectious Diseases Service, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Fundació Clinic per a la Recerca Biomèdica, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: de Lazzari
authors.affiliation: Immunology Department, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
authors.affiliation: Infectious Diseases Service, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Miró
mesh_terms: D000208:Acute Disease; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D061466:Lopinavir; D016572:Cyclosporine; D019438:Ritonavir