Correlation between circulating HIV-1 RNA and broad HIV-1 neutralizing antibody activity

To examine the relationship between HIV-1 antigenic load (plasma RNA copies/mL) and broad HIV-1 neutralizing antibody activity.

Plasma from 120 HIV-1-infected patients, including HIV-1 natural viral suppressors (similar to elite controllers), was tested for neutralization against 15 Tier 1/Tier 2 HIV-1 pseudoviruses. Broad HIV-1 neutralizing antibody activity was confirmed with immunoglobulin G and heterlogous clade testing (18 pseudoviruses from Clades A, C, and CRF02_AG). Statistical analysis was performed to determine factors associated with broad HIV-1 neutralizing antibody activity.

Ten individuals with broad HIV-1 neutralizing antibody activity were identified. These individuals had a median CD4 count of 589 cells per microliter (range 202-927), 1611 HIV-1 RNA copies per milliliter (range 110-8964), and 13 years since HIV diagnosis (range 1-22). There was a significant correlation between the presence of broadly neutralizing antibodies in those with HIV-1 RNA between 100 and 10,000 copies per milliliter compared with those <100 or >10,000 copies per milliliter (P = 0.0003 and 0.0245, respectively). Individuals with HIV-1 RNA 100-10,000 copies per milliliter had a higher number of Tier 2 viruses neutralized compared with the <100 or >10,000 copies per milliliter groups (P ≤ 0.0001 and P = 0.076, respectively). Male sex was associated with broad HIV-1 neutralizing antibody activity (P = 0.016).

These results indicate that low but persistent HIV antigen expression correlates with broad HIV-1 neutralizing antibody activity. At higher levels of plasma viremia, neutralization titers were diminished. Conversely, at lower levels, there seems to be insufficient antigen stimulation to maintain high neutralization titers. These findings may have important implications in furthering the understanding of the humoral response to HIV infection.