Plasma Levels of Complement Factor I and C4b Peptides Are Associated with HIV Suppression

Individuals who exhibit long-term HIV suppression and CD4 T-cell preservation without antiretroviral therapy are of great interest for HIV research. There is currently no robust method for rapid identification of these "HIV controller" subjects; however, HLA-B*57 (human leukocyte antigen (major histocompatibility complex), class I, B*57) genotype exhibits modest sensitivity for this phenotype. Complement C3b and C4b can influence HIV infection and replication, but studies have not examined their possible link to HIV controller status. We analyzed HLA-B*57 genotype and complement levels in HIV-positive patients receiving suppressive antiretroviral therapy, untreated HIV controllers, and HIV-negative subjects to identify factors associated with HIV controller status. Our results revealed that the plasma levels of three C4b-derived peptides and complement factor I outperformed all other assayed biomarkers for HIV controller identification, although we could not analyze the predictive value of biomarker combinations with the current sample size. We believe this rapid screening approach may prove useful for improved identification of HIV controllers.