EBioMedicine · 2026
Predictors of HIV reservoir size and decay dynamics in early-treated paediatric infection: a prospective, multicentre longitudinal cohort study.
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Reddy Kavidha, Domínguez-Rodríguez Sara, Molechan Chantal, Cotton Mark, Otwombe Kennedy, Lain Maria Grazia, Nhampossa Tacilta, Maiga Almoustapha Issiaka, Barnabas Shaun, Vaz Paula, Violari Avy, Fernández-Luis Sheila, Behuhuma Ngundu Osee, Sylla Mariam, Liberty Afaaf, Smit Theresa, Ording-Jespersen Gregory, Ismael Nalia, Giaquinto Carlo, Rossi Paolo, Kuhn Louise, Palma Paolo, Cotugno Nicola, Spyer Moira J, Magán Alvaro Ballesteros, Oletto Andrea, Dobbels Els, Rojo Pablo, Ndung'u Thumbi, Tagarro Alfredo, EPIICAL Consortium
Аннотация
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 (log10 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.
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 (log10 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.