High APRIL Levels Are Associated With Slow Disease Progression and Low Immune Activation in Chronic HIV-1-Infected Patients.

B-cell-activating factor (BAFF) has been determined to be involved in HIV-1 infection and is correlated with disease progression, while its homologous molecule, a proliferation-inducing ligand (APRIL), is less frequently reported, and its role remains unclear. We aimed to characterize the APRIL levels in subjects with different HIV-1 infection statuses and determine the relationships with disease progression and immune activation. The plasma levels of APRIL were compared among 17 long-term non-progressors (LTNPs), 17 typical progressors (TPs), 10 ART-treated patients, and 10 healthy donors (HDs). Seventeen LTNPs and a subset of TPs ( = 6) who initiated ART were assessed longitudinally. The correlations between the APRIL levels and markers of disease progression, B-cell count and specific antibody response, and markers of immune activation and functional cells were analyzed. The circulating APRIL levels were significantly elevated in the LTNPs relative to the TPs, ART-treated patients, and HDs. The longitudinal investigation revealed that the APRIL levels were decreased during follow-up in the LTNPs. ART did not significantly influence the APRIL levels. The levels of plasma APRIL were negatively correlated with the plasma HIV-1 viral load and cellular HIV-1 DNA levels and positively correlated with the CD4 T-cell count and CD4/CD8 ratio. An inverse correlation was observed between the APRIL and BAFF levels. Furthermore, the APRIL levels were negatively correlated with the frequency of activated CD8 T cells and levels of interferon gamma-induced protein 10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1). Finally, positive correlations were observed among the APRIL levels, the frequency of CD8CD28 T cells, and natural killer (NK) cell count. The APRIL levels were elevated in the LTNPs and negatively correlated with disease progression and immune activation, suggesting likely protective activity in HIV-1 infection.