{
  "abstract": "Background This study aims to characterize APOBEC-associated mutational patterns in individuals with longstanding HIV infection and prolonged exposure to antiretroviral therapy, and to assess their potential associations with clinical outcomes.Methods A total of 47 individuals with childhood-acquired HIV infection were enrolled and HIV-DNA samples were collected between March 2021 and July 2025 at Bambino Gesù Children’s Hospital (Rome, Italy). Next-generation sequencing (NGS) was performed with DeepChek® HIV Full PR/RT/INT Drug Resistance kit (ABL Diagnostics) on the MiSeq platform (Illumina). The prevalence of drug resistance mutations (DRMs) and signature APOBEC-related mutations (APO-Ms) (frequency higher than 5%) was evaluated through the DeepChek and HIVdb Stanford tools.Results Participants had a median age of 19 years (IQR: 14-25) and were mainly male (53.2%). Among them, 41 cases (87.2%) acquired the HIV-1 infection through vertical transmission. The most frequent HIV-1 subtype was BF (15;32%), followed by subtypes C and A1 (8;17% each one). Overall, 19 (40.4%) had undetectable HIV-RNA, 14(29.8%) showed <40 copies/mL and 14 (29.8%) >40 copies/mL, with a median viremia of 170 copies/mL (IQR: 142–17,133). While the median (IQR) HIV-DNA level was 551(181–1340) copies/10 6 CD4+T-cells. Among the 47 PWH, 26 (55.3%) had received early therapy, defined as initiation within the first year of life and an AIDS event was observed in 34%(16/47) individuals.Notably, early-treated individuals had a significantly lower HIV reservoir compared with those treated later, as reflected by lower median total HIV-DNA levels (387 [123–697] vs 1262 [367–1712] copies/106 CD4+ T cells; p=0.027).Overall, 57.4%(27/47) of individuals harboured at least one HIV-1 DRMs; in particular the NRTI, NNRTI and PI resistance were present in 19.1%, 38.3% and 8.5% of cases, respectively. 30/47 individuals (64%) showed at least one APOBEC-related mutation, mainly in the INSTI region (22; 73%), while 21/47 (45%) with at least one APOBEC-related stop codon.No significant differences were observed in APOBEC-associated mutations, when stratifying by early treatment initiation (38.5% vs 57.1%, p=0.163) and AIDS-defining events (56.2% vs 41.9%, p=0.893). Similar results were observed for stop codon frequency, both by early treatment (42.3% vs 47.6%; p=0.472) and AIDS events (43.8% vs 45.2%; p=0.587).Conclusions HIV-DNA sequencing revealed a significant prevalence of drug resistance mutations, as well as APOBEC-related mutations, particularly in the INSTI region.Early antiviral treatment was associated with significantly smaller HIV reservoir. The frequency of APOBEC-related mutations or stop codons seems not different in this relatively small cohort, yet their stable presence over the years in these young individuals without clinical progression suggests that studies with larger settings are required to define whether their presence affects the progression of the disease.",
  "authors": [
    {
      "affiliations": [
        "Microbiology and Diagnostic Immunology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "L Colagrossi"
    },
    {
      "affiliations": [
        "Unit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "C Dell’Angelo"
    },
    {
      "affiliations": [
        "Unit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "C Artini"
    },
    {
      "affiliations": [
        "Unit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "R Scutari"
    },
    {
      "affiliations": [
        "Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy"
      ],
      "name": "G Lorenzetti"
    },
    {
      "affiliations": [
        "Microbiology and Diagnostic Immunology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "V Fini"
    },
    {
      "affiliations": [
        "Unit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "V Fox"
    },
    {
      "affiliations": [
        "Microbiology and Diagnostic Immunology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "VC Di Maio"
    },
    {
      "affiliations": [
        "Microbiology and Diagnostic Immunology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "L Coltella"
    },
    {
      "affiliations": [
        "Microbiology and Diagnostic Immunology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "S Ranno"
    },
    {
      "affiliations": [
        "Microbiology and Diagnostic Immunology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "G Linardos"
    },
    {
      "affiliations": [
        "Microbiology and Diagnostic Immunology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "L Gentile"
    },
    {
      "affiliations": [
        "Microbiology and Diagnostic Immunology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "C Russo"
    },
    {
      "affiliations": [
        "Unit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "S Bernardi"
    },
    {
      "affiliations": [
        "Microbiology and Diagnostic Immunology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "CF Perno"
    }
  ],
  "title": "P190 Persistent APOBEC activity in children with longstanding HIV infection: characterization and correlation with clinical outcome",
  "uid": "6b7bf77f-2b3b-5e46-992d-026d305b95d9"
}