Publications & Reports

Effect of combination antiretroviral therapy on HIV-1-specific antibody-dependent cellular cytotoxicity responses in subtype B- and subtype C-infected cohorts.

Madhavi V, Kulkarni A, Shete A, Lee WS, Mclean MR, Kristensen AB, Ghate M, Wines BD, Hogarth PM, Parsons MS, Kelleher A, Cooper DA, Amin J, Emery S, Thakar M, Kent SJ

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 two cohorts (39 subtype B- and 47 subtype C-infected subjects) before and after two years of cART. ADCC analyses included an ELISA-based dimeric recombinant soluble (rs) FcγRIIIa-binding assay, antibody-dependent natural killer (NK) 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 two 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 six 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.

Link to publisher’s web site

Publication

  • Journal: Journal of Acquired Immune Deficiency Syndrome
  • Published: 01/07/2017
  • Volume: 75
  • Issue: 3
  • Pagination: 345-353

Authors