ADCC responses arising during acute/early HIV infection do not prevent rapid disease progression

MARÍA JULIA RUIZ; YANINA GHIGLIONE; MARÍA EUGENIA SOCIAS; NATALIA LAUFER; PEDRO CAHN; OMAR SUED; MARÍA MAGDALENA GHERARDI; HORACIO SALOMÓN; ANA MARÍA RODRÍGUEZ; GABRIELA TURK

Kuala Lumpur

Conferencia; 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2013

International AIDS Society

Background: Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of the humoral response postulated to contribute to anti-HIV immunity. Aim: to establish the potential role of ADCC-mediating HIV-specific antibodies in the control of acute/early primary HIV infection (PHI) and disease progression.  Methods: Plasma from 20 HIV+ subjects enrolled during PHI, obtained at enrollment and 12 months post-infection, 7 HAART-naïve chronically infected patients and 7 Elite Controllers (EC) were studied. PHI subjects were enrolled by the Argentinean PHI Cohort, and classified as ?progressors? if CD4 T-cell count dropped below 350 cellsl or experienced AIDS-related B/C events within 12 months post-infection (4 of them started HAART during this period). ADCC was analyzed using the rapid and flourometric ADCC assay (RFADCC) which relies in PKH-26 and CFSE staining of gp120-coated target cells (CEM?NKR) before the addition of subject?s plasma and effectors cells (PBMCs from healthy donors). Percentage of ADCC-killing and ADCC titres were determined. Data was compared inter- and intra-groups and correlated to viral load (VL) and CD4 counts using non-parametric statistics. Results: At baseline, 75% of PHI subjects had detectable ADCC responses (defined as titre≥1000) while all untreated subjects had detectable ADCC by 12 months post-infection. Median %ADCC-killing at 12 months post-infection was significantly higher compared to baseline (24% vs 7.2%, p=0.0006) and comparable to that of chronics (median 13%). Contrary, EC had significantly higher ADCC titres (median 105) than the other groups. Notably, instauration of HAART during the course of PHI was significantly associated with lower 12-month ADCC response (PHI treated vs PHI untreated median 6.7% and 24% respectively, p=0.03). No significantly differences were observed in ADCC responses between PHI progressors and non-progressors either at baseline or 12-month samples. Moreover, no significantly correlations were observed between the magnitude of baseline ADCC and CD4 counts or VL, at baseline and set-point determinations. Conclusions: Even though a protective role has been attributed to HIV-specific ADCC-mediating antibodies in different settings, our results suggest that, although these antibodies arise early during natural infection in humans, the magnitude of ADCC response might not be associated with improved resolution of acute infection or disease progression