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

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23 Citations (Scopus)

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/μL; 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.

Original languageEnglish
Pages (from-to)529-538
Number of pages10
JournalJournal of Infectious Diseases
Volume211
Issue number4
DOIs
Publication statusPublished - 15 Feb 2015
Externally publishedYes

Keywords

  • ADCC
  • ADP
  • cART
  • HIV
  • monocytes
  • NK cells

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