title: Antibody-dependent effector functions against HIV decline in subjects receiving antiretroviral therapy.
abstract: BACKGROUND
  Combination antiretroviral therapy (cART) effectively controls human immunodeficiency virus (HIV) infection but does not eliminate HIV, and lifelong treatment is therefore required. HIV-specific cytotoxic T lymphocyte (CTL) responses decline following cART initiation. Alterations in other HIV-specific immune responses that may assist in eliminating latent HIV infection, specifically antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP), are unclear.
  
  
  METHODS
  A cohort of 49 cART-naive HIV-infected subjects from Thailand (mean baseline CD4 count, 188 cells/µL; mean viral load, 5.4 log10 copies/mL) was followed for 96 weeks after initiating cART. ADCC and ADP assays were performed using serum samples obtained at baseline and after 96 weeks of cART.
  
  
  RESULTS
  A 35% reduction in HIV type 1 envelope (Env)-specific ADCC-mediated killing of target cells (P<.001) was observed after 96 weeks of cART. This was corroborated by a significant reduction in the ability of Env-specific ADCC antibodies to activate natural killer cells (P<.001). Significantly reduced ADP was also observed after 96 weeks of cART (P=.018).
  
  
  CONCLUSIONS
  This longitudinal study showed that cART resulted in significant reductions of HIV-specific effector antibody responses, including ADCC and ADP. Therapeutic vaccines or other immunomodulatory approaches may be required to improve antibody-mediated control of HIV during cART.
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Madhavi
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville.
authors.forename: Fernanda E
authors.initials: FE
authors.lastname: Ana-Sosa-Batiz
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville.
authors.forename: Sinthujan
authors.initials: S
authors.lastname: Jegaskanda
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Center
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville.
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Winnall
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Parsons
authors.affiliation: Thai Red Cross AIDS Research Centre, HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.affiliation: Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.affiliation: Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.affiliation: Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
authors.forename: Denise
authors.initials: D
authors.lastname: Hsu
authors.affiliation: Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia Medical Research Council Clinical Trials Unit, Department of Infection and Population Health, University College London, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Pett
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville.
authors.forename: Ivan
authors.initials: I
authors.lastname: Stratov
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville.
authors.forename: Marit
authors.initials: M
authors.lastname: Kramski
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects* / Q000276:immunology*; D015331:Cohort Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008137:Longitudinal Studies; D009000:Monocytes / Q000276:immunology; D019562:Viral Load; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D007074:Immunoglobulin G; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1
keywords: ADCC; ADP; HIV; NK cells; cART; monocytes