Publications & Reports

Antibody-dependent effector functions against HIV decline in subjects receiving antiretroviral therapy.

Vijaya Madhavi, Fernanda E Ana-Sosa-Batiz, Sinthujan Jegaskanda, Rob J Center, Wendy R Winnall, Matthew S Parsons, Jintanat Ananworanich, David A Cooper, Anthony D Kelleher, Denise Hsu, Sarah Pett, Ivan Stratov, Marit Kramski, Stephen J Kent
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville.

Abstract

BACKGROUND: Combination antiretroviral therapy (cART) effectively controls human immunodeficiency virus (HIV) infection but does not eliminate HIV, and lifelong treatment is therefore required. HIV-specific cytotoxic T lymphocyte (CTL) responses decline following cART initiation. Alterations in other HIV-specific immune responses that may assist in eliminating latent HIV infection, specifically antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP), are unclear. METHODS: A cohort of 49 cART-naive HIV-infected subjects from Thailand (mean baseline CD4 count, 188 cells/microL; mean viral load, 5.4 log10 copies/mL) was followed for 96 weeks after initiating cART. ADCC and ADP assays were performed using serum samples obtained at baseline and after 96 weeks of cART. RESULTS: A 35% reduction in HIV type 1 envelope (Env)-specific ADCC-mediated killing of target cells (P<.001) was observed after 96 weeks of cART. This was corroborated by a significant reduction in the ability of Env-specific ADCC antibodies to activate natural killer cells (P<.001). Significantly reduced ADP was also observed after 96 weeks of cART (P=.018). CONCLUSIONS: This longitudinal study showed that cART resulted in significant reductions of HIV-specific effector antibody responses, including ADCC and ADP. Therapeutic vaccines or other immunomodulatory approaches may be required to improve antibody-mediated control of HIV during cART.

Publication

  • Journal: The Journal of Infectious Diseases
  • Published: 15/02/2015
  • Volume: 211
  • Issue: 4
  • Pagination: 529-538

Author

Health Issue