Early and Highly Suppressive Antiretroviral Therapy Are Main Factors Associated With Low Viral Reservoir in European Perinatally HIV-Infected Children

Alfredo Tagarro, Man Chan, Paola Zangari, Bridget Ferns, Caroline Foster, Anita De Rossi, Eleni Nastouli, María A Muñoz-Fernández, Diana Gibb, Paolo Rossi, Carlo Giaquinto, Abdel Babiker, Claudia Fortuny, Riccardo Freguja, Nicola Cotugno, Ali Judd, Antoni Noguera-Julian, María Luisa Navarro, María José Mellado, Nigel KleinPaolo Palma, Pablo Rojo

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/10 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
Pages (from-to)269-276
Number of pages8
JournalJournal of acquired immune deficiency syndromes (1999)
Volume79
Issue number2
DOIs
Publication statusPublished - Oct 1 2018

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

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Early and Highly Suppressive Antiretroviral Therapy Are Main Factors Associated With Low Viral Reservoir in European Perinatally HIV-Infected Children. / Tagarro, Alfredo; Chan, Man; Zangari, Paola; Ferns, Bridget; Foster, Caroline; De Rossi, Anita; Nastouli, Eleni; Muñoz-Fernández, María A; Gibb, Diana; Rossi, Paolo; Giaquinto, Carlo; Babiker, Abdel; Fortuny, Claudia; Freguja, Riccardo; Cotugno, Nicola; Judd, Ali; Noguera-Julian, Antoni; Navarro, María Luisa; Mellado, María José; Klein, Nigel; Palma, Paolo; Rojo, Pablo.

In: Journal of acquired immune deficiency syndromes (1999), Vol. 79, No. 2, 01.10.2018, p. 269-276.

Research output: Contribution to journalArticle

Tagarro, A, Chan, M, Zangari, P, Ferns, B, Foster, C, De Rossi, A, Nastouli, E, Muñoz-Fernández, MA, Gibb, D, Rossi, P, Giaquinto, C, Babiker, A, Fortuny, C, Freguja, R, Cotugno, N, Judd, A, Noguera-Julian, A, Navarro, ML, Mellado, MJ, Klein, N, Palma, P & Rojo, P 2018, 'Early and Highly Suppressive Antiretroviral Therapy Are Main Factors Associated With Low Viral Reservoir in European Perinatally HIV-Infected Children', Journal of acquired immune deficiency syndromes (1999), vol. 79, no. 2, pp. 269-276. https://doi.org/10.1097/QAI.0000000000001789
Tagarro, Alfredo ; Chan, Man ; Zangari, Paola ; Ferns, Bridget ; Foster, Caroline ; De Rossi, Anita ; Nastouli, Eleni ; Muñoz-Fernández, María A ; Gibb, Diana ; Rossi, Paolo ; Giaquinto, Carlo ; Babiker, Abdel ; Fortuny, Claudia ; Freguja, Riccardo ; Cotugno, Nicola ; Judd, Ali ; Noguera-Julian, Antoni ; Navarro, María Luisa ; Mellado, María José ; Klein, Nigel ; Palma, Paolo ; Rojo, Pablo. / Early and Highly Suppressive Antiretroviral Therapy Are Main Factors Associated With Low Viral Reservoir in European Perinatally HIV-Infected Children. In: Journal of acquired immune deficiency syndromes (1999). 2018 ; Vol. 79, No. 2. pp. 269-276.
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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/10 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.",
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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 - 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

PY - 2018/10/1

Y1 - 2018/10/1

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/10 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/10 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.

U2 - 10.1097/QAI.0000000000001789

DO - 10.1097/QAI.0000000000001789

M3 - Article

C2 - 30211778

VL - 79

SP - 269

EP - 276

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 2

ER -