Early and Highly Suppressive Antiretroviral Therapy Are Main Factors Associated With Low Viral Reservoir in European Perinatally HIV-Infected Children
Por:
Tagarro A, Chan M, Zangari P, Ferns B, Foster C, De Rossi A, Nastouli E, Muñoz-Fernández MA, Gibb D, Rossi P, Giaquinto C, Babiker A, Fortuny-Guasch C, Freguja R, Cotugno N, Judd A, Noguera-Julian A, Navarro ML, Mellado MJ, Klein N, Palma P, Rojo P and EPIICAL Consortium
Publicada:
1 oct 2018
Ahead of Print:
26 jun 2018
Resumen:
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 log(10) 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] %, log(10) 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 6 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.
Filiaciones:
Tagarro A:
Department of Pediatrics, Hospital 12 de Octubre, Fundación para la Investigación Biomédica del Hospital Universitario 12 de Octubre. Madrid, Spain
Biomedical School. Uiversidad Europea de Madrid. Madrid, Spain
Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain
Chan M:
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials Methodology, London, UK
Zangari P:
Academic Department of Pediatrics (DPUO), Research Unit in Congenital and Perinatal Infection, Children's Hospital Bambino Gesù, Rome, Italy
Ferns B:
UCL/UCLH NIHR Biomedical Research Centre
Foster C:
Imperial College Healthcare NHS Trust
De Rossi A:
University of Padova, Section of Oncology and Immunology DiSCOG, Padova, Italy
Nastouli E:
UCL Great Ormond Sstreet Institute of Child Health, London UK
Muñoz-Fernández MA:
Immunology Section, InmunoBioloy Molecular Laboratory, Hospital General Universitario Gregorio Marañón, Spanish HIV HGM BioBank, IiSGM, Madrid, Spain
Gibb D:
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials Methodology, London, UK
Rossi P:
Academic Department of Pediatrics (DPUO), Research Unit in Congenital and Perinatal Infection, Children's Hospital Bambino Gesù, Rome, Italy
Giaquinto C:
Department of Women and Child Health, University of Padova, Padova, Italy
Babiker A:
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials Methodology, London, UK
Fortuny-Guasch C:
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. Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain. CIBER de Epidemiología y Salud Pública Ciberesp, Spain
Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain
Freguja R:
University of Padova, Section of Oncology and Immunology DiSCOG, Padova, Italy
Cotugno N:
Academic Department of Pediatrics (DPUO), Research Unit in Congenital and Perinatal Infection, Children's Hospital Bambino Gesù, Rome, Italy
Judd A:
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials Methodology, London, UK
Noguera-Julian A:
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. Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain. CIBER de Epidemiología y Salud Pública Ciberesp, Spain
Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain
Navarro ML:
Pediatric Infectious Diseases Unit, Hospital Universitario Gregorio Marañón, Madrid, Spain
Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain
Mellado MJ:
Pediatrics, Immunodeficiencies and Infectious Diseases Unit, Hospital Universitario La Paz, Madrid, Spain
Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain
Klein N:
UCL Great Ormond Sstreet Institute of Child Health, London UK
Palma P:
Academic Department of Pediatrics (DPUO), Research Unit in Congenital and Perinatal Infection, Children's Hospital Bambino Gesù, Rome, Italy
Rojo P:
Department of Pediatrics, Hospital 12 de Octubre, Fundación para la Investigación Biomédica del Hospital Universitario 12 de Octubre. Madrid, Spain
Medical School. Universidad Complutense de Madrid. Madrid, Spain
Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain
Green Submitted, hybrid
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