Analysis of Proviral HIV DNA and Its Role in HIV-1 Associated Neurocognitive Impairment

HIV-associated neurocognitive impairment persists despite effective antiretroviral therapy. Intact proviruses contain the replication-competent reservoir whose persistence remains the true barrier to an HIV cure, but defective proviruses may retain transcriptional potential that contributes to chronic inflammation. Most studies focus on total HIV DNA burden, which may not capture biologically relevant differences. CD14+ Monocytes can traffic across the blood-brain barrier, potentially contributing to CNS immune activation. This study evaluates whether the proviral composition is associated with neurocognitive performance. PBMC samples were obtained from 12 ART-treated individuals enrolled in a local observational neuroHIV study. PBMCs were magnetically separated into monocyte and non-monocyte fractions, yielding 36 matched samples across whole PBMCs, CD14+, and CD14-. 5’ defective, 3’ defective/hypermutated, and intact HIV-1 DNA reservoirs were measured using the intact proviral DNA assay. Intact provirus was detectable in 22% of samples, whereas 3’ defective and 5’ defective proviruses were detectable in 69% and 64% of samples, respectively. The CD14+ log10-transformed 3’:intact ratio showed the strongest inverse association with Neuropsychological test Z scores.