Antibody-Dependent Effector Functions Against HIV Decline in Subjects Receiving Antiretroviral Therapy

作者：Madhavi Vijaya; Ana Sosa Batiz Fernanda E; Jegaskanda Sinthujan; Center Rob J; Winnall Wendy R; Parsons Matthew S; Ananworanich Jintanat; Cooper David A; Kelleher Anthony D; Hsu Denise; Pett Sarah; Stratov Ivan; Kramski Marit; Kent Stephen J^*

来源：Journal of Infectious Diseases, 2015, 211(4): 529-538.

DOI：10.1093/infdis/jiu486

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

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/mu L; 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.

• 出版日期2015-2-15