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

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.