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Background:  HIV-1-associated dementia (HAD) continues to develop in individuals despite treatment with HAART. Monocytes/macrophages (M/MФ) can harbor proviral DNA that is not eradicated by HAART. To determine whether HAD is associated with the level of HIV-1 infection within circulating leukocytes, we quantified HIV-1 DNA (HIV DNA) copy number in peripheral blood mononuclear cells (PBMC), and in PBMC subsets. 

Methods:  A cross-sectional analysis of the HIV DNA copy number was performed within the Hawaii Aging with HIV Cohort, comparing participants with HAD to those with normal cognition. Real-time PCR assays assessing HIV DNA copy number per million cells were performed on PBMC and subsets. 

Results: Individuals with HAD (n = 27) had a median (interquartile range) of 9.11 (37.20) HIV DNA per 10⁶ PBMC compared to 0.49 (0.89) HIV DNA per 10⁶ PBMC in individuals with normal cognition (n = 22). Using a univariate analysis in the subset of individuals with undetectable viral load (HAD = 11; normal cognition = 13), the odds ratio of HAD attributable to HIV DNA copy number was 2.76 (1.28 to 5.94), p < 0.01). Preliminary analysis of a small subset of patients (n = 5) suggested that the primary source of HIV DNA may be the activated M/MФ (CD14⁺/CD16⁺) subset. 

Conclusions:  These findings suggest a potentially important association between circulating provirus and HAD.

Keywords: dementia; provirus; DNA