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Strong sex bias in elite control of paediatric HIV infection

Vieira, Vinicius A.a,*; Zuidewind, Peterb,*; Muenchhoff, Maximiliana,c,d; Roider, Juliaa; Millar, Janea; Clapson, Margarete; Van Zyl, Anriettef; Shingadia, Delanee; Adland, Emilya; Athavale, Rohina; Grayson, Nicholasa; Ansari, M. Azimg; Brander, Christianh,i,j; Guash, Claudia Fortunyk; Naver, Larsl,m; Puthanakit, Thanyaween,o,p; Songtaweesin, Wipaporn Nataliep; Ananworanich, Jintanatq,r,s,t; Peluso, Deniseu; Thomé, Beatrizv; Pinto, Jorgew; Jooste, Pieterf; Tudor-Williams, Garethx; Cotton, Mark F.b; Goulder, Philipa,y

doi: 10.1097/QAD.0000000000002043
CLINICAL SCIENCE
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Background: Reports of posttreatment control following antiretroviral therapy (ART) have prompted the question of how common immune control of HIV infection is in the absence of ART. In contrast to adult infection, where elite controllers have been very well characterized and constitute approximately 0.5% of infections, very few data exist to address this question in paediatric infection.

Methods: We describe 11 ART-naive elite controllers from 10 cohorts of HIV-infected children being followed in South Africa, Brazil, Thailand, and Europe.

Results: All but one of the elite controllers (91%) are females. The median age at which control of viraemia was achieved was 6.5 years. Five of these 11 (46%) children lost control of viraemia at a median age of 12.9 years. Children who maintained control of viraemia had significantly higher absolute CD4+ cell counts in the period of elite control than those who lost viraemic control. On the basis of data available from these cohorts, the prevalence of elite controllers in paediatric infection is estimated to be 5–10-fold lower than in adults.

Conclusion: Although conclusions are limited by the study design, these data suggest that, whilst paediatric elite control can be achieved, compared with adult elite controllers, this occurs rarely, and takes some years after infection to achieve. Also, loss of immune control arises in a high proportion of children and often relatively rapidly. These findings are consistent with the more potent antiviral immune responses observed in adults and in females.

aDepartment of Paediatrics, University of Oxford, Oxford, UK

bStellenbosch University, Cape Town, South Africa

cMax von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University Munich

dGerman Center for Infection Research (DZIF), partner site Munich, Germany

eDepartment of Paediatric Infectious Diseases, Great Ormond Street Hospital for Children, London, UK

fDepartment of Paediatrics, Kimberley Hospital, Kimberley, South Africa

gThe Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK

hIrsiCaixa - AIDS Research Institute, Badalona

iUniversitat de Vic-Universitat Central de Catalunya, Vic

jInstitució Catalana de Recerca i Estudis Avançats, Barcelona

kUnidad de Enfermedades Infecciosas, Servicio de Pediatría, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain

lDepartment of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm

mDepartment of Pediatrics, Karolinska University Hospital, Stockholm, Sweden

nThe HIV Netherlands Australia Thailand Research Collaboration

oDepartment of Pediatrics, Faculty of Medicine, Chulalongkorn University

pCenter of Excellence for Pediatric Infectious Diseases and Vaccines

qSEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand

rUS Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring

sHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA

tDepartment of Global Health, University of Amsterdam, Amsterdam, the Netherlands

uInstitute of Infectology Emilio Ribas , Sao Paulo

vInfectious Diseases Department, School of Medicine, University of Sao Paulo, Sao Paulo

wFederal University of Minas Gerais, Belo Horizonte, Brazil

xDepartment of Paediatrics, Imperial College, London, UK

yHIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal (UKZN), Durban, South Africa.

Correspondence to Philip Goulder, MA, FRCPCH, DPhil, FMedSci, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK. E-mail: philip.goulder@paediatrics.ox.ac.uk

Received 3 July, 2018

Accepted 11 September, 2018

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