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

被引:12
|
作者
Madhavi, Vijaya [1 ]
Kulkarni, Archana [2 ]
Shete, Ashwini [2 ]
Lee, Wen S. [1 ]
Mclean, Milla R. [1 ]
Kristensen, Anne B. [1 ]
Ghate, Manisha [2 ]
Wines, Bruce D. [3 ,4 ,5 ]
Hogarth, Phillip M. [3 ,4 ,5 ]
Parsons, Matthew S. [1 ]
Kelleher, Anthony [6 ,7 ]
Cooper, David A. [6 ]
Amin, Janaki [6 ]
Emery, Sean [6 ]
Thakar, Madhuri [2 ]
Kent, Stephen J. [1 ,8 ,9 ,10 ]
机构
[1] Univ Melbourne, Dept Microbiol & Immunol, Peter Doherty Inst Infect & Immun, 792 Elizabeth St, Parkville, Vic 3010, Australia
[2] Natl AIDS Res Inst, Dept Immunol & Serol, Pune, Maharashtra, India
[3] Burnet Inst, Ctr Biomed Res, Melbourne, Vic, Australia
[4] Monash Univ, Dept Immunol, Cent Clin Sch, Melbourne, Vic, Australia
[5] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia
[6] Univ New South Wales, Kirby Inst, Sydney, NSW, Australia
[7] St Vincents Ctr Appl Med Res, Darlinghurst, NSW, Australia
[8] Monash Univ, Melbourne Sexual Hlth Clin, Carlton, Vic, Australia
[9] Monash Univ, Alfred Hosp, Infect Dis Dept, Cent Clin Sch, Carlton, Vic, Australia
[10] Univ Melbourne, ARC Ctr Excellence Convergent Bionano Sci & Te, Melbourne, Vic, Australia
关键词
HIV-1; subtype B; subtype C; cART; ADCC; FcgR; influenza; Australia; India; DECAY KINETICS; INFLUENZA; HIV-1; DECLINE; INDIVIDUALS; EFFICACY; VACCINE; CELLS;
D O I
10.1097/QAI.0000000000001380
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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) Fc gamma RIIIa-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 rsFc gamma RIIIa 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/mu L (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.
引用
收藏
页码:345 / 353
页数:9
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