Caroline Foster1, Sara Domínguez-Rodríguez2, Alfredo Tagarro2, Triantafylia Gkouleli3, Judith Heaney3,4, Sarah Watters3, Alasdair Bamford5,6, Katy Fidler7, Marisa Navarro8, Anita De Rossi9, Paolo Palma10, Eleni Nastouli3,6, Paolo Rossi10, Carlo Giaquinto9, Pablo Rojo2. 1. Imperial College Healthcare NHS Trust, London, United Kingdom. 2. Pediatric Infectious Diseases Unit, Fundación para la Investigación Biomédica del Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain. 3. Department of Population, Policy and Practice, University College London Great Ormond Street Institute of Child Health, London, United Kingdom. 4. Advanced Pathogen Diagnostics Unit, University College London Hospitals NHS Foundation Trust, London, United Kingdom. 5. Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom. 6. University College London Great Ormond Street Institute of Child Health, London, United Kingdom. 7. Brighton and Sussex Medical School, Falmer, United Kingdom. 8. Pediatric Infectious Disease Unit, Institute of Investigation, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain. 9. Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, Padova, Italy. 10. Division of Immune and Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Pediatrico Bambino Gesu, Rome, Italy.
Abstract
BACKGROUND: Strategies aimed at antiretroviral therapy (ART)-free remission will target individuals with a limited viral reservoir. We investigated factors associated with low reservoir measured as total human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells (PBMCs) in perinatal infection (PaHIV). METHODS: Children from 7 European centers in the Early Treated Perinatally HIV Infected Individuals: Improving Children's Actual Life (EPIICAL) consortium who commenced ART aged <2 years, and remained suppressed (viral load [VL] <50 copies/mL) for >5 years were included. Total HIV-1 DNA was measured by quantitative polymerase chain reaction per million PBMCs. Factors associated with total HIV-1 DNA were analyzed using generalized additive models. Age, VL at ART initiation, and baseline CD4% effects were tested including smoothing splines to test nonlinear association. RESULTS: Forty PaHIV, 27 (67.5%) female 21 (52.5%) Black/Black African, had total HIV-1 DNA measured; median 12 (IQR, 7.3-15.4) years after ART initiation. Eleven had total HIV-1 DNA <10 copies/106 PBMCs. HIV-1 DNA levels were positively associated with age and VL at ART initiation, baseline CD4%, and Western blot antibody score. Age at ART initiation presented a linear association (coefficient = 0.10 ± 0.001, P ≤ .001), the effect of VL (coefficient = 0.35 ± 0.1, P ≤ .001) noticeable >6 logs. The effect of CD4% (coefficient = 0.03 ± 0.01, P = .049) was not maintained >40%. CONCLUSIONS: In this PaHIV cohort, reduced total HIV-1 DNA levels were associated with younger age and lower VL at ART initiation. The impact of early-infant treatment on reservoir size persists after a decade of suppressive therapy.
BACKGROUND: Strategies aimed at antiretroviral therapy (ART)-free remission will target individuals with a limited viral reservoir. We investigated factors associated with low reservoir measured as total human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells (PBMCs) in perinatal infection (PaHIV). METHODS:Children from 7 European centers in the Early Treated Perinatally HIV Infected Individuals: Improving Children's Actual Life (EPIICAL) consortium who commenced ART aged <2 years, and remained suppressed (viral load [VL] <50 copies/mL) for >5 years were included. Total HIV-1 DNA was measured by quantitative polymerase chain reaction per million PBMCs. Factors associated with total HIV-1 DNA were analyzed using generalized additive models. Age, VL at ART initiation, and baseline CD4% effects were tested including smoothing splines to test nonlinear association. RESULTS: Forty PaHIV, 27 (67.5%) female 21 (52.5%) Black/Black African, had total HIV-1 DNA measured; median 12 (IQR, 7.3-15.4) years after ART initiation. Eleven had total HIV-1 DNA <10 copies/106 PBMCs. HIV-1 DNA levels were positively associated with age and VL at ART initiation, baseline CD4%, and Western blot antibody score. Age at ART initiation presented a linear association (coefficient = 0.10 ± 0.001, P ≤ .001), the effect of VL (coefficient = 0.35 ± 0.1, P ≤ .001) noticeable >6 logs. The effect of CD4% (coefficient = 0.03 ± 0.01, P = .049) was not maintained >40%. CONCLUSIONS: In this PaHIV cohort, reduced total HIV-1 DNA levels were associated with younger age and lower VL at ART initiation. The impact of early-infant treatment on reservoir size persists after a decade of suppressive therapy.
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