{
  "abstract": "Background Long-acting injectable cabotegravir plus rilpivirine (LA-CAB/RPV) represents a paradigm shift in HIV management. This single-center study conducted an in-depth longitudinal immunological evaluation of PLWH switching to long-acting injectable cabotegravir plus rilpivirine (LA-CAB/RPV).Material and Methods Three time points were considered: before LA-CAB/RPV (T0), after 12 (T12) and 24 months (T24). Plasma HIV-1 RNA and total cell-associated HIV-1 DNA levels were evaluated. T-cell and monocyte/macrophage subsets were analyzed by flow cytometry. Plasma biomarkers of neuronal (NfL) and astrocyte (GFAP) damage, monocyte/macrophage activation (sCD163, sCD14), and BBB permeability (MMP-9, TIMP-1) were investigated using microfluidic next-generation ELISA. Each time point was compared to healthy donors (HD).Results Twenty-six ART-experienced, aviremic PWH and 32 HDs were enrolled. At each time points, PLWH had higher intermediate monocyte counts compared to HD. Lower pDC and slanDC counts were observed compared to HD as well as higher sCD163, sCD14, NfL and GFAP plasma levels. No differences in MMP-9 and TIMP-1 plasma levels were found (see table 1).The longitudinal evaluation revealed no virological failure, nor any differences in the total cell-associated HIV-1 DNA levels. At T12, significant increases in pDC and classical monocyte counts were observed. Conversely, significant decreases were observed in non-classical monocyte counts, as well as in the NfL plasma levels compared to T0. At T24, significant increases in pDC counts were observed. Conversely, significant decreases were observed in intermediate monocyte counts, as well as in the sCD14 plasma levels compared to T0.Positive correlations were found between non-classical monocyte counts and plasma levels of NfL (ρ=0.3819, p=0.0096) and GFAP (ρ=0.3869, p=0.0087) as well as between sCD163 and NfL plasma levels (ρ=0.4081, p=0.0040), sCD14 and NfL plasma levels (ρ=0.4488, p=0.0014). No correlations were found between total cell-associated HIV-1 DNA and monocyte/macrophage subsets nor with CNS inflammation/damage blood biomarkers.Conclusions Switching to LA-CAB/RPV maintains virological suppression and HIV-DNA stability over 24 months. The significant reduction in plasma NfL levels, paralleled by decreased monocyte activation, suggests a potential attenuation of subclinical neuronal damage. This highlights a possible neuroprotective effect linked to immunomodulation of the monocyte-CNS axis. LA-CAB/RPV may thus offer benefits beyond adherence, potentially mitigating HIV-associated neuroinflammation and long-term CNS comorbidities. These findings support the safety of LA regimens regarding immune reconstitution and CNS health, warranting further longitudinal investigation.Abstract OC54 Table 1Study population",
  "authors": [
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy",
        "University Hospital Policlinico Umberto I, Sapienza University of Rome, Rome, Italy"
      ],
      "name": "MA Zingaropoli"
    },
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy"
      ],
      "name": "M Guardiani"
    },
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy"
      ],
      "name": "A Carraro"
    },
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy"
      ],
      "name": "F Dominelli"
    },
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy"
      ],
      "name": "M Antonacci"
    },
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy"
      ],
      "name": "M Proietti"
    },
    {
      "affiliations": [
        "SM Goretti Hospital, Sapienza University of Rome, Latina, Italy"
      ],
      "name": "C Del Borgo"
    },
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy"
      ],
      "name": "E Tortellini"
    },
    {
      "affiliations": [
        "SM Goretti Hospital, Sapienza University of Rome, Latina, Italy"
      ],
      "name": "R Marocco"
    },
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy"
      ],
      "name": "G Mancarella"
    },
    {
      "affiliations": [
        "SM Goretti Hospital, Sapienza University of Rome, Latina, Italy"
      ],
      "name": "L Ansaldo"
    },
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy"
      ],
      "name": "O Turriziani"
    },
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy"
      ],
      "name": "MR Ciardi"
    },
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy"
      ],
      "name": "CM Mastroianni"
    },
    {
      "affiliations": [
        "Sapienza University of Rome, Rome, Italy"
      ],
      "name": "M Lichtner"
    }
  ],
  "title": "OC54 Two-year immunological and neuroinflammatory outcomes of switching to long-acting cabotegravir/rilpivirine in PLWH",
  "uid": "7b8cf1c7-2e5e-583d-903e-1516b7cf155c"
}