B-defensin genomic copy number is associated with HIV load and immune reconstitution in sub-Saharan Africans

AIDS, caused by the retrovirus human immunodeficiency virus (HIV), is the leading cause of death of economically active people (age, 15–59 years) in sub-Saharan Africa. The host genetic variability of immune response to HIV and immune reconstitution following initiation of highly active antiretroviral therapy(HAART) is poorly understood. Here we focused on copy number variation of the β-defensin genes, which have been shown to have anti-HIV activity, and are important chemoattractants for Th17 lymphocytes via the chemokine receptor CCR6. We determined β-defensin gene copy number for 1002 Ethiopian and Tanzanian patients. We show that higher β-defensin copy number variation is associated with increased HIV load prior to HAART (P = .005) and poor immune reconstitution following initiation of HAART (P = .003). We suggest a model where variable amounts of β-defensin expression by mucosal cells, due to gene copy number variation, alters the efficacy of recruitment of Th17 lymphocytes to the site of infection, altering the dynamics of infection.