title: Effect of Combination Antiretroviral Therapy on HIV-1-specific Antibody-Dependent Cellular Cytotoxicity Responses in Subtype B- and Subtype C-Infected Cohorts.
abstract: There is growing interest in immune therapies to clear the latent HIV-1 after combination antiretroviral therapy (cART). There is limited information on the effect of cART on antibody-dependent cellular cytotoxicity (ADCC), and no studies have directly compared ADCC in HIV-1 subtype B- and subtype C-infected subjects. The effect of improving immunocompetence on ADCC to influenza also remains unexplored.
  
  
  
  The effect of cART on HIV-1- and influenza-specific ADCC was analyzed in 2 cohorts (39 subtype B- and 47 subtype C-infected subjects) before and after 2 years of cART. ADCC analyses included an enzyme-linked immunosorbent assay-based dimeric recombinant soluble (rs) FcγRIIIa-binding assay, antibody-dependent natural killer cell activation assay, and ADCC-mediated killing assays.
  
  
  
  HIV-1 subtype B and C Env-specific antibody binding to dimeric rsFcγRIIIa were reduced in subtypes B- and C-infected cohorts after 2 years of cART (both P < 0.05). Reduced ADCC-mediated killing of target cells expressing subtype B Env in the subtype B-infected cohort (P = 0.003) was observed after 96 weeks of cART, but not of subtype C Env in the subtype C-infected cohort. A greater reduction in ADCC was detected in subjects with baseline CD4 counts >300 cells/μL (P < 0.05). The resolving immunodeficiency after 96 weeks of cART resulted in improved HA-specific ADCC to 6 strains of influenza (all P < 0.01).
  
  
  
  cART results in HIV-1 antigen loss and reductions in HIV-1 Env-specific antibodies with Fc functionality in both subtype B- and C-infected subjects, particularly in immunocompetent subjects. Simultaneously, cART improves ADCC to diverse strains of influenza, suggesting reduction in influenza disease after cART.
authors.affiliation: *Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia; †Department of Immunology and Serology, National AIDS Research Institute, Pune, India; ‡Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia; §Department of Immunology, Monash University Central Clinical School, Melbourne, Victoria, Australia; ‖Department of Pathology, the University of Melbourne, Melbourne, Victoria, Australia; ¶Kirby Institute, University of New South Wales, Sydney, Australia; #St Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia; **Melbourne Sexual Health Clinic and Infectious Diseases Department, Alfred Hospital, Central Clinical School, Monash University, Carlton, Victoria, Australia; and ††ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, the University of Melbourne, Melbourne, Australia.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Madhavi
authors.forename: Archana
authors.initials: A
authors.lastname: Kulkarni
authors.forename: Ashwini
authors.initials: A
authors.lastname: Shete
authors.forename: Wen S
authors.initials: WS
authors.lastname: Lee
authors.forename: Milla R
authors.initials: MR
authors.lastname: Mclean
authors.forename: Anne B
authors.initials: AB
authors.lastname: Kristensen
authors.forename: Manisha
authors.initials: M
authors.lastname: Ghate
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Wines
authors.forename: Phillip M
authors.initials: PM
authors.lastname: Hogarth
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Parsons
authors.forename: Anthony
authors.initials: A
authors.lastname: Kelleher
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.forename: Madhuri
authors.initials: M
authors.lastname: Thakar
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D015483:HIV Antibodies; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D054299:env Gene Products, Human Immunodeficiency Virus