Alfredo Tagarro1,2,3, Man Chan4, Paola Zangari5, Bridget Ferns6, Caroline Foster7, Anita De Rossi8, Eleni Nastouli9, María A Muñoz-Fernández10, Diana Gibb4, Paolo Rossi5, Carlo Giaquinto11, Abdel Babiker5, Claudia Fortuny3,12,13, Riccardo Freguja8, Nicola Cotugno5, Ali Judd4, Antoni Noguera-Julian3,12,13,14, María Luisa Navarro3,15, María José Mellado3,16, Nigel Klein9, Paolo Palma5, Pablo Rojo1,3,17. 1. Department of Pediatrics, Hospital 12 de Octubre, Fundación para la Investigación Biomédica del Hospital Universitario 12 de Octubre, Madrid, Spain. 2. Biomedical School, Uiversidad Europea de Madrid, Madrid, Spain. 3. Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain. 4. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, United Kingdom. 5. Academic Department of Pediatrics (DPUO), Research Unit in Congenital and Perinatal Infection, Children's Hospital Bambino Gesù, Rome, Italy. 6. UCL/UCLH NIHR Biomedical Research Centre. 7. Imperial College Healthcare NHS Trust. 8. University of Padova, Section of Oncology and Immunology DiSCOG, Padova, Italy. 9. UCL Great Ormond Street Institute of Child Health, London United Kingdom. 10. Immunology Section, InmunoBioloy Molecular Laboratory, Hospital General Universitario Gregorio Marañón, Spanish HIV HGM BioBank, IiSGM, Madrid, Spain. 11. Department of Women and Child Health, University of Padova, Padova, Italy. 12. Malalties Infeccioses i Resposta Inflamatòria Sistèmica En pediatria, Unitat d'Infeccions, Servei de Pediatria, Institut de Recerca, Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain. 13. Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain. 14. CIBER de Epidemiología y Salud Pública Ciberesp, Spain. 15. Pediatric Infectious Diseases Unit, Hospital Universitario Gregorio Marañón, Madrid, Spain. 16. Pediatrics, Immunodeficiencies and Infectious Diseases Unit, Hospital Universitario La Paz, Madrid, Spain. 17. Medical School, Universidad Complutense de Madrid, Madrid, Spain.
Abstract
BACKGROUND: Future strategies aiming to achieve HIV-1 remission are likely to target individuals with small reservoir size. SETTING: We retrospectively investigated factors associated with HIV-1 DNA levels in European, perinatally HIV-infected children starting antiretroviral therapy (ART) <6 months of age. METHODS: Total HIV-1 DNA was measured from 51 long-term suppressed children aged 6.3 years (median) after initial viral suppression. Factors associated with log10 total HIV-1 DNA were analyzed using linear regression. RESULTS: At ART initiation, children were aged median [IQR] 2.3 [1.2-4.1] months, CD4% 37 [24-45] %, CD8% 28 [18-36] %, log10 plasma viral load (VL) 5.4 [4.4-5.9] copies per milliliter. Time to viral suppression was 7.98 [4.6-19.3] months. After suppression, 13 (25%) children had suboptimal response [≥2 consecutive VL 50-400 followed by VL <50] and/or experienced periods of virological failure [≥2 consecutive VL ≥400 followed by VL <50]. Median total HIV-1 DNA was 43 [6195] copies/10 PBMC. Younger age at therapy initiation was associated with lower total HIV-1 DNA (adjusted coefficient [AC] 0.12 per month older, P = 0.0091), with a month increase in age at ART start being associated with a 13% increase in HIV DNA. Similarly, a higher proportion of time spent virally suppressed (AC 0.10 per 10% higher, P = 0.0022) and the absence of viral failure/suboptimal response (AC 0.34 for those with fail/suboptimal response, P = 0.0483) were associated with lower total HIV-1 DNA. CONCLUSIONS: Early ART initiation and a higher proportion of time suppressed are linked with lower total HIV-1 DNA. Early ART start and improving adherence in perinatally HIV-1-infected children minimize the size of viral reservoir.
BACKGROUND: Future strategies aiming to achieve HIV-1 remission are likely to target individuals with small reservoir size. SETTING: We retrospectively investigated factors associated with HIV-1 DNA levels in European, perinatally HIV-infectedchildren starting antiretroviral therapy (ART) <6 months of age. METHODS: Total HIV-1 DNA was measured from 51 long-term suppressed children aged 6.3 years (median) after initial viral suppression. Factors associated with log10 total HIV-1 DNA were analyzed using linear regression. RESULTS: At ART initiation, children were aged median [IQR] 2.3 [1.2-4.1] months, CD4% 37 [24-45] %, CD8% 28 [18-36] %, log10 plasma viral load (VL) 5.4 [4.4-5.9] copies per milliliter. Time to viral suppression was 7.98 [4.6-19.3] months. After suppression, 13 (25%) children had suboptimal response [≥2 consecutive VL 50-400 followed by VL <50] and/or experienced periods of virological failure [≥2 consecutive VL ≥400 followed by VL <50]. Median total HIV-1 DNA was 43 [6195] copies/10 PBMC. Younger age at therapy initiation was associated with lower total HIV-1 DNA (adjusted coefficient [AC] 0.12 per month older, P = 0.0091), with a month increase in age at ART start being associated with a 13% increase in HIV DNA. Similarly, a higher proportion of time spent virally suppressed (AC 0.10 per 10% higher, P = 0.0022) and the absence of viral failure/suboptimal response (AC 0.34 for those with fail/suboptimal response, P = 0.0483) were associated with lower total HIV-1 DNA. CONCLUSIONS: Early ART initiation and a higher proportion of time suppressed are linked with lower total HIV-1 DNA. Early ART start and improving adherence in perinatally HIV-1-infectedchildren minimize the size of viral reservoir.
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