β-Defensin genomic copy number is associated with HIV viral load and immune reconstitution in sub-Saharan Africans

AIDS, caused by the retrovirus HIV, is the leading cause of death of economically-active people (age 15 59) in sub-Saharan Africa. It is characterised by high HIV viral load and reduced (<200 cells/mm3) CD4 + T-cell count. b-defensins are broad-spectrum antimicrobial genes that are also chemotactic for dendritic cells and T-cells through the CCR6. b-defensin genes have previously been shown to be copy number variable, that is, different individuals have different numbers of the same gene. In this cohort study we analysed the relationship between b-defensin genomic copy number and HIV viral load immediately prior to initiation of retroviral treatment in 627 Ethiopian and 325 Tanzanian HIV patients, some co-infected with tuberculosis. We also measured the response to Highly Active Antiretroviral Therapy (HAART) by measuring follow-up CD4+ T-cell counts and viral load counts in a subsection of these patients. We found that high b-defensin copy number was associated with increased baseline HIV viral load, independent of co-infection with tuberculosis and population of origin. We also found that high b-defensin copy number was associated with impaired immune reconstitution after initiation of HAART, as measured by CD4 count up to 48 weeks follow-up and virological failure (persistence of viremia with viral load >200 copies/ml). Given the known chemotactic role of b-de-fensins, our data suggest a model where b-defensins recruit HIV- permissive Th17 lymphocytes to mucosal sites via the chemokine receptor CCR6. E. Hollox and E. Aklillu are joint senior authors