title: Safety, immunogenicity and efficacy assessment of HIV immunotherapy in a multi-centre, double-blind, randomised, Placebo-controlled Phase Ib human trial.
abstract: BACKGROUND
  Combination antiretroviral therapy (cART) is the main therapeutic management tool for HIV/AIDS. Despite its success in controlling viral load and disease progression, cART is expensive, associated with a range of significant side effects and depends for its efficacy on the patient's life-long commitment to high levels of treatment adherence. Immunotherapeutic agents can provide potential solutions to these shortcomings. Here we describe a Phase Ib trial of HIV-v, a synthetic immunotherapy that elicits T- and B-cell effector responses against HIV infected cells.
  
  
  METHODS
  Fifty-nine cART-naive HIV-infected males aged 18-50 years with viral load of 5000-500,000 copies/ml and CD4 counts >350/μl were recruited for this multi-centre, randomised, double blind study. Volunteers received one low (250 μg) or high (500 μg) dose of HIV-v, either alone or adjuvanted (ISA-51). Safety, immunogenicity, CD4 count and viral load were monitored over 168 Days.
  
  
  RESULTS
  HIV-v was well tolerated and the adjuvanted formulations elicited IgG responses in up to 75% of volunteers. The high adjuvanted dose also elicited cellular responses in 45% of tested volunteers. In these responding subjects viral loads were reduced by over 1 log (p=0.04) compared to Placebo and non-responders. No changes in CD4 count were observed.
  
  
  CONCLUSIONS
  HIV-v is safe and can elicit T- and B-cell responses in ART-naive HIV patients that significantly reduce viral load. Improved dosing regimens and further research on long term efficacy are required, but HIV-v appears to have potential as an immunotherapeutic anti-viral agent. Trial registered as EudraCT-2009-010593-37 (ClinicalTrials.gov Identifier: NCT01071031).
authors.affiliation: St. Stephen's Centre, Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.forename: Julie
authors.initials: J
authors.lastname: Fox
authors.forename: Christine
authors.initials: C
authors.lastname: Bowman
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: Chloe
authors.initials: C
authors.lastname: Orkin
authors.forename: Edmund
authors.initials: E
authors.lastname: Wilkins
authors.forename: Akil
authors.initials: A
authors.lastname: Jackson
authors.forename: Olga
authors.initials: O
authors.lastname: Pleguezuelos
authors.forename: Stuart
authors.initials: S
authors.lastname: Robinson
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Stoloff
authors.forename: Wilson
authors.initials: W
authors.lastname: Caparrós-Wanderley
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D006678:HIV / Q000276:immunology / Q000302:isolation & purification; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects* / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D019562:Viral Load; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D010919:Placebos
keywords: CD4 count; HIV; Immunotherapy; Phase Ib clinical trial; Viral load