HIV viral suppression is associated with delayed disease progression and reduced transmission. HIV controllers suppress HIV viral load to low levels without antiretroviral treatment (ART). We used a massively-multiplexed antibody profiling system (VirScan) to compare the antibody profiles in HIV controllers, viremic non-controllers, and non-controllers who were suppressed on ART. The VirScan assay provides quantitative information on antibody binding to >3,300 peptides spanning the HIV genome.
Antibody reactivity was assessed in 13 elite controllers, 27 viremic controllers, 21 non-controllers who were virally suppressed on ART, and 12 viremic non-controllers (Discovery Cohort). Antibody reactivity to selected peptides was quantified in a second cohort that included 29 elite controllers and 37 non-controllers who were virally suppressed on ART (Validation Cohort). Antibody reactivity was also assessed in 298 samples from 53 non-controllers who had viral load data from longitudinal visits that was used to determine viral load set point.
In the Discovery Cohort, we identified 62 peptides that were preferentially targeted in HIV controllers compared to non-controllers. In the Validation Cohort, combined antibody reactivity to these peptides was also higher in elite controllers compared to non-controllers who were virally suppressed on ART. The reactivity of antibodies to the 62 peptides was similar among HIV controllers who did or did not have the protective HLA-B*57 allele. All but one of the 62 peptides were grouped into seven clusters of homologous peptides. The clusters were located in gp120 (two clusters), gp41, p17, p24, vpu, and integrase. Higher antibody reactivity to a subset of the peptides in the p17 cluster was significantly associated with lower viral load set points in the group of longitudinally-followed non-controllers.
A comprehensive, unbiased assessment of antibody reactivity to HIV peptides spanning the viral genome identified clusters of homologous peptides that were preferentially targeted in HIV controllers and non-controllers who had lower viral load set points. Further research is needed to characterize antibodies that target these peptides and evaluate T cell targeting of these epitopes. This research will provide new insights into natural control of HIV infection and may inform research on immune-based interventions for HIV prevention and treatment.