Predictors of HIV reservoir size and decay dynamics in early-treated paediatric infection: a prospective, multicentre longitudinal cohort study

@article{reddy2026predictors,
  title = {{Predictors of HIV reservoir size and decay dynamics in early-treated paediatric infection: a prospective, multicentre longitudinal cohort study}},
  author = {Kavidha Reddy and Sara Domínguez-Rodríguez and Chantal Molechan and Mark Cotton and Kennedy Otwombe and Maria Grazia Lain and Tacilta Nhampossa and Almoustapha Issiaka Maiga and Shaun Barnabas and Paula Vaz and Avy Violari and Sheila Fernández-Luis and Ngundu Osee Behuhuma and Mariam Sylla and Afaaf Liberty and Theresa Smit and Gregory Ording-Jespersen and Nalia Ismael and Carlo Giaquinto and Paolo Rossi and Louise Kuhn and Paolo Palma and Nicola Cotugno and Moira J. Spyer and Alvaro Ballesteros Magán and Andrea Oletto and Els Dobbels and Pablo Rojo and Thumbi Ndung’u and Alfredo Tagarro and Viviana Giannuzzi and Anita Janse Van Rensburg and Yasmeen Akhalwaya and Nigel Klein and Nastasja Ramsagar and Senamile Makhari and Elisa López and Denise Naniche and Yacouba Aba Coulibaly and Caroline Foster and Helena Rabie and Pauline Amugue and Camille Brehin and Savita Pahwa and Elena Morrocchi and Eleni Nastouli and Fatoumata Tata and Matthias Lichterfeld and Loide Cardoso and Rizaam Meyer and Moherndran Archary and Oumar Dolo and Josue Togo and Kurt Smith and Mornay Isaacs and Ligia Estevao},
  journal = {eBioMedicine},
  year = {2026},
  month = oct,
  doi = {10.1016/j.ebiom.2026.106510},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S2352396426003944},
  note = {CC BY-NC-ND 4.0},
}

TY  - JOUR
TI  - Predictors of HIV reservoir size and decay dynamics in early-treated paediatric infection: a prospective, multicentre longitudinal cohort study
AU  - Kavidha Reddy
AU  - Sara Domínguez-Rodríguez
AU  - Chantal Molechan
AU  - Mark Cotton
AU  - Kennedy Otwombe
AU  - Maria Grazia Lain
AU  - Tacilta Nhampossa
AU  - Almoustapha Issiaka Maiga
AU  - Shaun Barnabas
AU  - Paula Vaz
AU  - Avy Violari
AU  - Sheila Fernández-Luis
AU  - Ngundu Osee Behuhuma
AU  - Mariam Sylla
AU  - Afaaf Liberty
AU  - Theresa Smit
AU  - Gregory Ording-Jespersen
AU  - Nalia Ismael
AU  - Carlo Giaquinto
AU  - Paolo Rossi
AU  - Louise Kuhn
AU  - Paolo Palma
AU  - Nicola Cotugno
AU  - Moira J. Spyer
AU  - Alvaro Ballesteros Magán
AU  - Andrea Oletto
AU  - Els Dobbels
AU  - Pablo Rojo
AU  - Thumbi Ndung’u
AU  - Alfredo Tagarro
AU  - Viviana Giannuzzi
AU  - Anita Janse Van Rensburg
AU  - Yasmeen Akhalwaya
AU  - Nigel Klein
AU  - Nastasja Ramsagar
AU  - Senamile Makhari
AU  - Elisa López
AU  - Denise Naniche
AU  - Yacouba Aba Coulibaly
AU  - Caroline Foster
AU  - Helena Rabie
AU  - Pauline Amugue
AU  - Camille Brehin
AU  - Savita Pahwa
AU  - Elena Morrocchi
AU  - Eleni Nastouli
AU  - Fatoumata Tata
AU  - Matthias Lichterfeld
AU  - Loide Cardoso
AU  - Rizaam Meyer
AU  - Moherndran Archary
AU  - Oumar Dolo
AU  - Josue Togo
AU  - Kurt Smith
AU  - Mornay Isaacs
AU  - Ligia Estevao
PY  - 2026
DA  - 2026/10/22
JO  - eBioMedicine
DO  - 10.1016/j.ebiom.2026.106510
UR  - https://linkinghub.elsevier.com/retrieve/pii/S2352396426003944
AB  - 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.
SN  - 2352-3964
ER  -