Effect of Combination Antiretroviral Therapy on HIV-1-specific Antibody-Dependent Cellular Cytotoxicity Responses in Subtype B- and Subtype C-Infected Cohorts

J Acquir Immune Defic Syndr. 2017 Jul 1;75(3):345-353. doi: 10.1097/QAI.0000000000001380.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antibody-Dependent Cell Cytotoxicity / drug effects*
  • Antibody-Dependent Cell Cytotoxicity / immunology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Cohort Studies
  • Drug Therapy, Combination
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Antibodies / immunology
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV-1 / drug effects
  • HIV-1 / immunology*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • T-Lymphocytes, Cytotoxic / drug effects
  • Treatment Outcome
  • Viral Load
  • Young Adult
  • env Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • Anti-HIV Agents
  • HIV Antibodies
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin G
  • env Gene Products, Human Immunodeficiency Virus