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The CARMA Study: Early Infant Antiretroviral Therapy-Timing Impacts on Total HIV-1 DNA Quantitation 12 Years Later

Foster, C; Domínguez-Rodríguez, S; Tagarro, A; Gkouleli, T; Heaney, J; Watters, S; Bamford, A; ... Early Treated Perinatally HIV Infected Individuals: Improving Ch; + view all (2020) The CARMA Study: Early Infant Antiretroviral Therapy-Timing Impacts on Total HIV-1 DNA Quantitation 12 Years Later. Journal of the Pediatric Infectious Diseases Society , Article piaa071. 10.1093/jpids/piaa071. (In press). Green open access

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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.

Type: Article
Title: The CARMA Study: Early Infant Antiretroviral Therapy-Timing Impacts on Total HIV-1 DNA Quantitation 12 Years Later
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jpids/piaa071
Publisher version: http://dx.doi.org/10.1093/jpids/piaa071
Language: English
Additional information: © The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http:// creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals. permissions@oup.com
Keywords: HIV reservoir, HIV-1, adolescents, children, early treated, viral suppression
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10112363
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