{
  "abstract": "Background: Early antiretroviral therapy (ART) after perinatal HIV infection can restrict reservoir size and diversity, offering potential for remission. We evaluated HIV-1 DNA dynamics up to four years of age and predictors of reservoir size in early-treated African children. Methods: In this prospective, multicentre cohort study, infants with perinatal HIV from South Africa, Mozambique, and Mali who initiated ART before 6 months of age and within 3 months of diagnosis were enrolled. Children were followed at 2, 6, 12, and 24 weeks, then biannually for 4 years. Total HIV-1 DNA in PBMCs was quantified longitudinally by droplet digital PCR in 207 children. The main outcomes were HIV-1 DNA reservoir size at year 3 (log 10 copies/million PBMC) and longitudinal HIV-1 DNA decay. Multivariable models were developed to identify predictors of reservoir size using generalised additive regression models, and decay dynamics were evaluated using mixed-effects Poisson models including random intercepts and viral load slopes. Findings: Of 207 children, 155 (75%) had >12 months of follow-up. HIV was diagnosed at a median age of 31 days (IQR: 0, 47) and ART started at 33 days (IQR: 23.5, 69.5). Nineteen of 155 (12.3%) had undetectable HIV-1 DNA at year 4. Median decay rate was −0.020 log10 copies/million cells/month (−0.212/year). Smaller reservoirs at year 3 were associated with lower pre-ART viral load (β = 0.26, 95% CI: 0.09, 0.43) and faster first-year HIV-1 DNA decay rate (β = 1.09, 95% CI: 0.02, 2.19), with trends toward smaller reservoirs among females (β = −0.41, 95% CI: −0.87, 0.04) and larger reservoirs among children whose mothers reported social challenges (β = 0.42, 95% CI: −0.04, 0.87). Faster decay correlated with longer time on ART, lower serial viral loads, sustained viral suppression >12 months, earlier ART initiation, and region (Mali). Maternal health issues correlated with slower decay. Eleven “excellent controllers” maintained durable viral suppression, immunological control, and undetectable total HIV-1 DNA at last follow-up. Interpretation: Early virological parameters may help identify children likely to develop smaller HIV reservoirs. Early ART is key to faster reservoir reduction. Maternal health issues influence reservoir decay, reflecting a parental legacy effect. Sex differences should be further explored to understand mechanisms of reservoir control. Children with sustained virological suppression, preserved immune status, and undetectable total HIV-1 DNA may represent candidates with favourable characteristics for HIV remission strategies, as these factors have been associated with a reduced burden of persistent HIV infection and have been observed in rare cases of post-treatment control. Funding: EPIICAL consortium through ViiV Healthcare and Penta Foundation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 56,
  "authors": [
    {
      "name": "Kavidha Reddy",
      "orcid": "0000-0002-7024-0574"
    },
    {
      "name": "Sara Domínguez-Rodríguez"
    },
    {
      "name": "Chantal Molechan"
    },
    {
      "name": "Mark Cotton"
    },
    {
      "name": "Kennedy Otwombe"
    },
    {
      "name": "Maria Grazia Lain"
    },
    {
      "name": "Tacilta Nhampossa"
    },
    {
      "name": "Almoustapha Issiaka Maiga"
    },
    {
      "name": "Shaun Barnabas"
    },
    {
      "name": "Paula Vaz"
    },
    {
      "name": "Avy Violari"
    },
    {
      "name": "Sheila Fernández-Luis"
    },
    {
      "name": "Ngundu Osee Behuhuma"
    },
    {
      "name": "Mariam Sylla"
    },
    {
      "name": "Afaaf Liberty"
    },
    {
      "name": "Theresa Smit"
    },
    {
      "name": "Gregory Ording-Jespersen"
    },
    {
      "name": "Nalia Ismael"
    },
    {
      "name": "Carlo Giaquinto"
    },
    {
      "name": "Paolo Rossi"
    },
    {
      "name": "Louise Kuhn"
    },
    {
      "name": "Paolo Palma"
    },
    {
      "name": "Nicola Cotugno"
    },
    {
      "name": "Moira J. Spyer"
    },
    {
      "name": "Alvaro Ballesteros Magán"
    },
    {
      "name": "Andrea Oletto"
    },
    {
      "name": "Els Dobbels"
    },
    {
      "name": "Pablo Rojo"
    },
    {
      "name": "Thumbi Ndung’u"
    },
    {
      "name": "Alfredo Tagarro"
    },
    {
      "name": "Viviana Giannuzzi"
    },
    {
      "name": "Anita Janse Van Rensburg"
    },
    {
      "name": "Yasmeen Akhalwaya"
    },
    {
      "name": "Nigel Klein"
    },
    {
      "name": "Nastasja Ramsagar"
    },
    {
      "name": "Senamile Makhari"
    },
    {
      "name": "Elisa López"
    },
    {
      "name": "Denise Naniche"
    },
    {
      "name": "Yacouba Aba Coulibaly"
    },
    {
      "name": "Caroline Foster"
    },
    {
      "name": "Helena Rabie"
    },
    {
      "name": "Pauline Amugue"
    },
    {
      "name": "Camille Brehin"
    },
    {
      "name": "Savita Pahwa"
    },
    {
      "name": "Elena Morrocchi"
    },
    {
      "name": "Eleni Nastouli"
    },
    {
      "name": "Fatoumata Tata"
    },
    {
      "name": "Matthias Lichterfeld"
    },
    {
      "name": "Loide Cardoso"
    },
    {
      "name": "Rizaam Meyer"
    },
    {
      "name": "Moherndran Archary"
    },
    {
      "name": "Oumar Dolo"
    },
    {
      "name": "Josue Togo"
    },
    {
      "name": "Kurt Smith"
    },
    {
      "name": "Mornay Isaacs"
    },
    {
      "name": "Ligia Estevao"
    }
  ],
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  "doi": "10.1016/j.ebiom.2026.106510",
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  "language": "en",
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  "pmcid": "PMC13715305",
  "pmid": "42913305",
  "published": "2026-10-22",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/evy2q8evrjf1z.ris",
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2406|HIV Research and Treatment",
      "subfield": "microbiology"
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  "title": "Predictors of HIV reservoir size and decay dynamics in early-treated paediatric infection: a prospective, multicentre longitudinal cohort study",
  "title_text": "Predictors of HIV reservoir size and decay dynamics in early-treated paediatric infection: a prospective, multicentre longitudinal cohort study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:38Z",
  "url": "https://research.draconitic.com/paper/evy2q8evrjf1z",
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