Circulating proviral HIV DNA and HIV-associated dementia

Objective: Individuals continue to develop HIV-1-associated dementia (HAD) despite treatment with highly active antiretroviral therapy (HAART). Monocytes/macrophages (M/MΦ) can harbor proviral DNA that is not eradicated by HAART. To determine if HAD is associated with the level of HIV-1 infection within circulating leukocytes, we quantified HIV-1 DNA copy number in peripheral blood mononuclear cells (PBMC), and in PBMC subsets. Design: Cross-sectional analysis within the Hawaii Aging with HIV Cohort comparing participants with HAD to those with normal cognition (NC). Methods: Real-time PCR assays assessing HIV DNA copy number/1 × 10⁶ 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 1 × 10⁶ PBMC compared to 0.49 (0.89) HIV DNA per 1 × 10⁶ PBMC in individuals with NC (n = 22). Using a univariate analysis in the subset of individuals with undetectable viral load (HAD, n = 11 ; NC, n = 13), the odds of HAD attributable to HIV DNA copy number was 2.76 (1.28-5.94), 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/MΦ (CD14/CD16) subset. Conclusions. These findings suggest a potentially important association between circulating provirus and HAD.