Early and highly suppressive antiretroviral therapy are main factors associated with low viral reservoir in European perinatally HIV-infected children

behalf of the EPIICAL Consortium

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)269-276
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume79
Issue number2
DOIs
StatePublished - Jan 1 2018

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HIV-1
HIV
Viral Load
DNA
Therapeutics
Secondary Prevention
Linear Models

Keywords

  • Children
  • Early treated
  • HIV DNA
  • HIV-1
  • Reservoir
  • Viral load

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Early and highly suppressive antiretroviral therapy are main factors associated with low viral reservoir in European perinatally HIV-infected children. / behalf of the EPIICAL Consortium.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 79, No. 2, 01.01.2018, p. 269-276.

Research output: Contribution to journalArticle

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title = "Early and highly suppressive antiretroviral therapy are main factors associated with low viral reservoir in European perinatally HIV-infected children",
abstract = "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.",
keywords = "Children, Early treated, HIV DNA, HIV-1, Reservoir, Viral load",
author = "{behalf of the EPIICAL Consortium} and Alfredo Tagarro and Man Chan and Paola Zangari and Bridget Ferns and Caroline Foster and {De Rossi}, Anita and Eleni Nastouli and Mu{\~n}oz-Fern{\'a}ndez, {Mar{\'i}a A.} and Diana Gibb and Paolo Rossi and Carlo Giaquinto and Abdel Babiker and Claudia Fortuny and Riccardo Freguja and Nicola Cotugno and Ali Judd and Antoni Noguera-Julian and Navarro, {Mar{\'i}a Luisa} and Mellado, {Mar{\'i}a Jos{\'e}} and Nigel Klein and Paolo Palma and Pablo Rojo and Alfredo Tagarro and Sarah Watters and Marcelin, {Anne Genevieve} and Vincent Calvez and Britta Wahren and Mark Cotton and Merlin Robb and Jintanat Ananworanich and Polly Claiden and Deenan Pillay and Deborah Persaud and {De Boer}, {Rob J.} and Thanyawee Puthanakit and Adriana Ceci and Viviana Giannuzzi and Kathrine Luzuriaga and Nicolas Chomont and Mark Cameron and Caterina Cancrini and Andrew Yates and Louise Kuhn and Avy Violari and Kennedy Otwombe and Francesca Rocchi",
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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

PY - 2018/1/1

Y1 - 2018/1/1

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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SN - 1525-4135

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