Intact HIV reservoir in monocytes is associated with cognitive function in virally suppressed women with HIV

Background: Monocytes are susceptible to HIV infection, form HIV reservoirs, and contribute to central nervous system complications (e.g., cognitive impairment) in virally suppressed women with HIV(vsWWH). However, it remains unknown if the quality and/or quantity of the monocyte reservoir contributes to cognition in vsWWH.

Methods: 62 vsWWH(mean age=56.1, SD=7.1; 93% Black, non-Hispanic; all HIV RNA <250 copies/mL) completed a cognitive test battery, blood draw, and whole blood immunophenotyping. Monocytes and CD4 T cells were isolated from a subset of 53 participants and the HIV reservoir was assessed using cell specific Intact Proviral DNA Assays(IPDA). Demographically-adjusted z-scores were calculated for each outcome using data from participants without HIV in the Women's Interagency HIV Study. Cognitive outcomes of interest included domain-specific and global z-scores.

Results: Thirty-Eight percent of vsWWH had detectable intact HIV genomes in monocytes(median=21.5 copies/million). Higher levels of intact HIV genomes per million monocytes were associated with poorer verbal memory(delayed recall: r=0.55, P=0.01; recognition: r=0.46, P=0.04), fine motor skills(r=0.50, P=0.03), and global function(r=0.47, P=0.04). Higher levels of intact HIV genomes in monocytes were associated with percent intermediate monocytes(r=0.60, P=0.008), and the ratio of intact per intermediate monocyte was associated with worse memory(r=-0.59, P=0.008). There were no associations between CD4 reservoir and cognition.

Discussion: The number of intact HIV genomes per million monocytes were related to poorer cognition and the percentage of intermediate monocytes. These findings suggest that the presence of HIV genomes in general do not relate to cognitive complications, but intact, and therefore potentially replication-competent HIV, may contribute to cognitive complications in vsWWH.