TY - JOUR
T1 - Early and highly suppressive antiretroviral therapy are main factors associated with low viral reservoir in European perinatally HIV-infected children
AU - behalf of the EPIICAL Consortium
AU - Tagarro, Alfredo
AU - Chan, Man
AU - Zangari, Paola
AU - Ferns, Bridget
AU - Foster, Caroline
AU - De Rossi, Anita
AU - Nastouli, Eleni
AU - Muñoz-Fernández, María A.
AU - Gibb, Diana
AU - Rossi, Paolo
AU - Giaquinto, Carlo
AU - Babiker, Abdel
AU - Fortuny, Claudia
AU - Freguja, Riccardo
AU - Cotugno, Nicola
AU - Judd, Ali
AU - Noguera-Julian, Antoni
AU - Navarro, María Luisa
AU - Mellado, María José
AU - Klein, Nigel
AU - Palma, Paolo
AU - Rojo, Pablo
AU - Tagarro, Alfredo
AU - Watters, Sarah
AU - Marcelin, Anne Genevieve
AU - Calvez, Vincent
AU - Wahren, Britta
AU - Cotton, Mark
AU - Robb, Merlin
AU - Ananworanich, Jintanat
AU - Claiden, Polly
AU - Pillay, Deenan
AU - Persaud, Deborah
AU - De Boer, Rob J.
AU - Puthanakit, Thanyawee
AU - Ceci, Adriana
AU - Giannuzzi, Viviana
AU - Luzuriaga, Kathrine
AU - Chomont, Nicolas
AU - Cameron, Mark
AU - Cancrini, Caterina
AU - Yates, Andrew
AU - Kuhn, Louise
AU - Violari, Avy
AU - Otwombe, Kennedy
AU - Rocchi, Francesca
N1 - Funding Information:
Supported by EPIICAL (Early-treated Perinatally HIV-infected Individuals: Improving Children’s Actual Life with Novel Immunotherapeutic Strategies) project, funded through an independent grant by ViiV Healthcare United Kingdom. This work is part of the EPIICAL project (http://www.epiical.org/), supported by PENTA-ID foundation (http://penta-id.org/), funded through an independent grant by ViiV Healthcare United Kingdom.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018
Y1 - 2018
N2 - 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/106 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.
AB - 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/106 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.
KW - Children
KW - Early treated
KW - HIV DNA
KW - HIV-1
KW - Reservoir
KW - Viral load
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U2 - 10.1097/QAI.0000000000001789
DO - 10.1097/QAI.0000000000001789
M3 - Article
C2 - 30211778
AN - SCOPUS:85054434383
VL - 79
SP - 269
EP - 276
JO - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology
JF - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology
SN - 1525-4135
IS - 2
ER -