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Establishment and Replenishment of the Viral Reservoir in Perinatally HIV-1-infected Children Initiating Very Early Antiretroviral Therapy
Martínez-Bonet, Marta (Hospital General Universitario Gregorio Marañón)
Puertas, Maria Carmen (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Fortuny, Claudia (Hospital Sant Joan de Déu)
Ouchi, Dan (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Mellado, Maria José (Hospital Universitario Infantil LA PAZ)
Rojo, Pablo (Servicio de Pediatría. Hospital 12 de Octubre)
Noguera-Julian, Antoni (Hospital Sant Joan de Déu)
Muñoz-Fernández, Ma Angeles (Hospital General Universitario Gregorio Marañón)
Martinez-Picado, Javier (Institució Catalana de Recerca i Estudis Avançats)
Universitat Autònoma de Barcelona

Date: 2015
Abstract: Initiation of combined antiretroviral therapy within the first 12 weeks of life in vertically human immunodeficiency virus type 1-infected children favors the establishment of low-level proviral reservoirs. Nevertheless, treatment discontinuation in these patients may lead to rapid and irreversible expansion of reservoir size. Background. Combination antiretroviral therapy (cART) generally suppresses the replication of the human immunodeficiency virus type 1 (HIV-1) but does not cure the infection, because proviruses persist in stable latent reservoirs. It has been proposed that low-level proviral reservoirs might predict longer virologic control after discontinuation of treatment. Our objective was to evaluate the impact of very early initiation of cART and temporary treatment interruption on the size of the latent HIV-1 reservoir in vertically infected children. Methods. This retrospective study included 23 perinatally HIV-1-infected children who initiated very early treatment within 12 weeks after birth (n = 14), or early treatment between week 12 and 1 year (n = 9). We measured the proviral reservoir (CD4 + T-cell-associated HIV-1 DNA) in blood samples collected beyond the first year of sustained virologic suppression. Results. There is a strong positive correlation between the time to initiation of cART and the size of the proviral reservoir. Children who initiated cART within the first 12 weeks of life showed a proviral reservoir 6-fold smaller than children initiating cART beyond this time (P <. 01). Rapid virologic control after initiation of cART also limits the size of the viral reservoir. However, patients who underwent transient treatment interruptions showed a dramatic increase in the size of the viral reservoir after discontinuation. Conclusions. Initiation of cART during the first 12 weeks of life in perinatally HIV-1-infected children limits the size of the viral reservoir. Treatment interruptions should be undertaken with caution, as they might lead to fast and irreversible replenishment of the viral reservoir.
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
Subject: HIV-1 ; Vertical infection ; Early antiretroviral therapy ; Viral reservoir
Published in: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, Vol. 61 (june 2015) , p. 1169-1178, ISSN 1537-6591

DOI: 10.1093/cid/civ456
PMID: 26063721

10 p, 473.8 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles

 Record created 2018-01-31, last modified 2020-11-01

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