Abstract Body


Monocytes play a significant role in the early immune response during acute HIV infection (AHI), and the extent myeloid cell dysregulation has implications for long-term central nervous system (CNS) outcomes. We hypothesized that monocytes carrying HIV RNA would show increased transcriptional dysregulation during AHI.


We isolated ultra-high purity monocytes from 25-40 million PBMC aliquots of 17 participants in the Thai RV254/SEARCH010 AHI cohort obtained prior to ART during AHI (Fiebig I-V) to measure genome-wide transcriptome expression and epigenetic profiles and assess the detection of cell-associated (CA-) HIV RNA. Mann Whitney and T tests examined demographic differences between those with detectable and undetectable monocyte CA-HIV RNA. Differential expression analyses compared participants with detectable versus undetectable HIV RNA using an FDR adjusted P value.


Participants had a median age of 26 yrs, median log10 plasma viral load of 5.55 copies/mL (IQR: 4.87-6.51), CD4+ T cell count of 451 cells/mm^3 (324.5-644), and CD4/CD8 ratio of 0.64 (0.37-1.09). 11/17 participants had detectable CSF HIV RNA levels in supernatant. 41% were in Fiebig stages I/II, and 59% in stages III-V. 8/17 (47%) had detectable monocyte HIV CA-RNA. Those with detectable monocyte HIV RNA trended higher in plasma viral load (6.17 vs 4.79; p=0.05) and lower in CD4/CD8 ratio (0.52 vs 1.02; p=0.06), but there was no difference in CD4 count or Fiebig stage between groups. 70 genes were significantly differentially expressed in monocytes comparing participants with detectable versus undetectable monocyte HIV RNA at an FDR adjusted P < 0.05. Notably, expression of immunomodulatory inflammatory gene CD38, cell surface receptor gene CD40, interferon-induced gene MX1, and viral RNA sensor IFIH1 were significantly higher in participants with detectable versus undetectable monocyte cell-associated HIV RNA. Moreover, we identified that expression of pro-apoptotic BCL-2 protein family gene PMAIP1 and transcription factors SP3 and ETV3 were significantly decreased in participants with detectable versus undetectable monocyte CA-HIV RNA.


In AHI, detectable monocyte HIV RNA is linked to notable transcriptional dysregulation, potentially impacting long-term myeloid cell programming and CNS outcomes. Identifying individuals with a higher transcriptionally active HIV myeloid reservoir warrants further study to guide early myeloid targeted treatment strategies and prevention of inflammation.