HIV-DNA content in different CD4+ T cell subsets correlates with CD4+ cell: CD8+ cell ratio or lenght of efficient treatment

HIV establishes a latent infection at different degrees within naive (TN) or central (TCM) and effector memory (TEM) CD4+ T cell. Our main aim was to find which factors can influence intracellular viral reservoir in different CD4+ T-cell subsets, in HIV+ patients.
We enrolled 32 HIV+ patients successfully treated, with a CD4+ T-cell count more than 500 cells/ml and plasma viremia undetectable. Proviral HIV-DNA, the amount of cells expressing signal-joint T-cell receptor rearrangement excision circles (sjTREC) and telomere length were quantified by droplet digital PCR in highly purified, sorted CD4+ T-cell subsets; plasma IL-7 and IL-15 were measured by ELISA.
We identified TN, TCM, TEM and TEMRA CD4+ T cells on the basis of the expression of CD45RA and CCR7. HIV-DNA was significantly lower in TN cells compared with TCM or to TEM. Conversely, TN cells contained more sjTREC compared with TCM or to TEM; no appreciable changes were observed in telomere length. HIV-DNA content was significantly higher in TN and TCM cells, but not in TEM, from patients with shorter time of treatment, or in those with lower CD4+ : CD8+ ratio.
In conclusion, length of treatment or recovery of CD4+ : CD8+ ratio significantly influences viral reservoir in both TN and TCM. Measuring HIV-DNA in purified lymphocyte populations allows a better monitoring of HIV reservoir and could be useful for designing future eradication strategies.

Lara Gibellini
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