Plasma LL-37 correlates with vitamin D and is reduced in human immunodeficiency virus-1 infected individuals not receiving antiretroviral therapy

Low levels of the vitamin D-regulated antimicrobial peptide cathelicidin (LL-37) may negatively impact the immune status of human immunodeficiency virus-1 (HIV-1) infected individuals (HIV+). We compared plasma LL-37 levels in healthy controls (HIV-) and HIV+ individuals on or off antiretroviral therapies (ARTs) (ART+ and ART-, respectively), and evaluated the relationship between vitamin D and LL-37 levels. In this cross-sectional study, levels of LL-37, 25-hydroxycholecalciferol [25(OH)D₃] and 1,25-dihydroxycholecalciferol [1,25(OH)₂D₃] were measured from an initial cohort of 18 healthy controls and 10 HIV+/ART- individuals. Because this cohort lacked HIV+/ART+ subjects, LL-37 was also quantified from a second cohort of 10 HIV+/ART- and 13 HIV+/ART+ individuals. LL-37 levels were significantly lower in the HIV+/ART- group compared to the healthy controls (P = 0.01). A direct relationship was observed between LL-37 and both 25(OH)D₃ and 1,25(OH)₂D₃. The level of 25(OH)D₃ was predictive of higher LL-37 (P = 0.04) and for any given level of 25(OH)D₃, HIV+/ART- subjects averaged 20 % lower LL-37 compared to the healthy controls (P = 0.045). For any given level of 1,25(OH)₂D₃, HIV+/ART- subjects averaged 25 % lower LL-37 compared to the healthy controls (P = 0.018), although 1,25(OH)₂D₃ was not predictive of higher LL-37 (P = 0.28). Finally, LL-37 levels were significantly lower in the HIV+/ART- group compared to the HIV+/ART+ group from the second cohort (P = 0.045). Untreated HIV infection may contribute to lower LL-37 levels, independent of vitamin D levels. ART treatment may potentially mitigate this decrease in LL-37 levels.