Effect of Combination Antiretroviral Therapy on HIV-1-specific Antibody-Dependent Cellular Cytotoxicity Responses in Subtype B- and Subtype C-Infected Cohorts
| Autor: | David A. Cooper, Bruce D. Wines, P.M. Hogarth, Janaki Amin, Sean Emery, Vijaya Madhavi, Matthew S. Parsons, Milla R. McLean, Stephen J. Kent, Ashwini Shete, Anthony D. Kelleher, Manisha Ghate, Archana Kulkarni, Wen Shi Lee, Madhuri Thakar, Anne B. Kristensen |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male 0301 basic medicine Cart Anti-HIV Agents Enzyme-Linked Immunosorbent Assay HIV Infections Hemagglutinin Glycoproteins Influenza Virus chemical and pharmacologic phenomena HIV Antibodies Immunoglobulin G Cohort Studies Young Adult 03 medical and health sciences 0302 clinical medicine Antigen immune system diseases Humans Medicine Pharmacology (medical) Antibody-dependent cell-mediated cytotoxicity biology business.industry Antibody-Dependent Cell Cytotoxicity env Gene Products Human Immunodeficiency Virus virus diseases Middle Aged Viral Load Virology Killer Cells Natural Treatment Outcome 030104 developmental biology Infectious Diseases Immunology HIV-1 biology.protein Drug Therapy Combination Female Immunocompetence Antibody business Natural killer cell activation Viral load T-Lymphocytes Cytotoxic 030215 immunology |
| Zdroj: | JAIDS Journal of Acquired Immune Deficiency Syndromes. 75:345-353 |
| ISSN: | 1525-4135 |
| Popis: | 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 P0.05). 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 counts300 cells/μL (P0.05). The resolving immunodeficiency after 96 weeks of cART resulted in improved HA-specific ADCC to 6 strains of influenza (all P0.01).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. |
| Databáze: | OpenAIRE |
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