Abstract: Individuals infected with HIV type 1 are more likely than noninfected individuals to develop depression. HIV lowers brain-derived neurotrophic factor (BDNF), a neurotrophic factor whose receptors play a crucial role in the pathophysiology of depression. Therefore, we examined whether a single-nucleotide polymorphism in the BDNF gene (rs56164415) and related receptors TrkB (rs1212171) and p75NTR (rs2072446) were associated with depression in HIV-infected individuals. A total of 1365 HIV-positive and 371 HIV-negative female subjects were included. The distribution of alleles was analyzed independently in African Americans (non-Hispanic) and Caucasians (non-Hispanic). We have found that the absence of depressive symptoms in HIV-positive subjects is associated with a genetic variation of the TrkB but not with BDNF or p75NTR genes. This mutation explains 0.8% and 4.4% of the variability for the absence of depression in African Americans and Caucasians, respectively.