Long-term virological outcomes, failure and acquired resistance in a large cohort of Ugandan children

M. H. W. Huibers, C. Kityo, R. S. Boerma, E. Kaudha, K. C. E. Sigaloff, S. N. Balinda, S. Bertagnolio, R. Nakanjako, P. Mugyenyi, J. C. J. Calis, M. Boele van Hensbroek, T. F. Rinke de Wit

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVES: To evaluate long-term virological failure (VF) and drug resistance among HIV-infected Ugandan children on first-line ART. METHODS: In a multicentre prospective cohort study, viral load (VL) and drug resistance mutations (DRMs) were investigated at baseline and 6 monthly intervals in children (age ≤ 12 years). VF (two consecutive VLs >1000 copies/mL or death after 6 months of ART) was defined as early VF (0-24 months of ART) or late VF (25-48 months of ART). An active regimen was defined as partially active if the genotypic susceptibility score (GSS) was <3. RESULTS: Between 2010 and 2011, 316 children were enrolled. Viral suppression was achieved in 75.8%, 71.5%, 72.6% and 69.2% at 12, 24, 36 and 48 months. VF occurred in 111/286 (38.8%), of which 67.6% was early and 32.4% late VF. Early VF was associated with a partially active regimen at baseline (OR 6.0, 95% CI 1.9-18.5), poor adherence (OR 3.1, 95% CI 1.3-7.4) and immunodeficiency (OR 3.3, 95% CI 1.1-10.2). Late VF was associated with age >3 years (OR 2.5, 95% CI 1.0-6.6) and WHO stage 3/4 (OR 4.2, 95% CI 1.4-13.4). Acquired DRMs were detected in 27.0% before 24 months, versus 14.4% after 24 months (P < 0.001). A total of 92.2% of the children with early VF, versus 56.2% with late VF, had a partially active regimen (P < 0.001). CONCLUSIONS: VF rates were high, occurred predominantly in the first 24 months and appeared to increase again in year four. Risk factors and patterns of early VF/DRMs were different from those of late VF/DRMs. Virological control may improve by close monitoring and prompt switching to second-line therapy in the first 24 months. Late VF may be prevented by early start of ART.
Original languageEnglish
Pages (from-to)3035-3043
JournalThe Journal of antimicrobial chemotherapy
Volume74
Issue number10
DOIs
Publication statusPublished - 1 Oct 2019

Cite this

Huibers, M. H. W. ; Kityo, C. ; Boerma, R. S. ; Kaudha, E. ; Sigaloff, K. C. E. ; Balinda, S. N. ; Bertagnolio, S. ; Nakanjako, R. ; Mugyenyi, P. ; Calis, J. C. J. ; Boele van Hensbroek, M. ; Rinke de Wit, T. F. / Long-term virological outcomes, failure and acquired resistance in a large cohort of Ugandan children. In: The Journal of antimicrobial chemotherapy. 2019 ; Vol. 74, No. 10. pp. 3035-3043.
@article{6fd72ec542404d75b6da91d99db928a4,
title = "Long-term virological outcomes, failure and acquired resistance in a large cohort of Ugandan children",
abstract = "OBJECTIVES: To evaluate long-term virological failure (VF) and drug resistance among HIV-infected Ugandan children on first-line ART. METHODS: In a multicentre prospective cohort study, viral load (VL) and drug resistance mutations (DRMs) were investigated at baseline and 6 monthly intervals in children (age ≤ 12 years). VF (two consecutive VLs >1000 copies/mL or death after 6 months of ART) was defined as early VF (0-24 months of ART) or late VF (25-48 months of ART). An active regimen was defined as partially active if the genotypic susceptibility score (GSS) was <3. RESULTS: Between 2010 and 2011, 316 children were enrolled. Viral suppression was achieved in 75.8{\%}, 71.5{\%}, 72.6{\%} and 69.2{\%} at 12, 24, 36 and 48 months. VF occurred in 111/286 (38.8{\%}), of which 67.6{\%} was early and 32.4{\%} late VF. Early VF was associated with a partially active regimen at baseline (OR 6.0, 95{\%} CI 1.9-18.5), poor adherence (OR 3.1, 95{\%} CI 1.3-7.4) and immunodeficiency (OR 3.3, 95{\%} CI 1.1-10.2). Late VF was associated with age >3 years (OR 2.5, 95{\%} CI 1.0-6.6) and WHO stage 3/4 (OR 4.2, 95{\%} CI 1.4-13.4). Acquired DRMs were detected in 27.0{\%} before 24 months, versus 14.4{\%} after 24 months (P < 0.001). A total of 92.2{\%} of the children with early VF, versus 56.2{\%} with late VF, had a partially active regimen (P < 0.001). CONCLUSIONS: VF rates were high, occurred predominantly in the first 24 months and appeared to increase again in year four. Risk factors and patterns of early VF/DRMs were different from those of late VF/DRMs. Virological control may improve by close monitoring and prompt switching to second-line therapy in the first 24 months. Late VF may be prevented by early start of ART.",
author = "Huibers, {M. H. W.} and C. Kityo and Boerma, {R. S.} and E. Kaudha and Sigaloff, {K. C. E.} and Balinda, {S. N.} and S. Bertagnolio and R. Nakanjako and P. Mugyenyi and Calis, {J. C. J.} and {Boele van Hensbroek}, M. and {Rinke de Wit}, {T. F.}",
year = "2019",
month = "10",
day = "1",
doi = "10.1093/jac/dkz266",
language = "English",
volume = "74",
pages = "3035--3043",
journal = "The Journal of antimicrobial chemotherapy",
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Huibers, MHW, Kityo, C, Boerma, RS, Kaudha, E, Sigaloff, KCE, Balinda, SN, Bertagnolio, S, Nakanjako, R, Mugyenyi, P, Calis, JCJ, Boele van Hensbroek, M & Rinke de Wit, TF 2019, 'Long-term virological outcomes, failure and acquired resistance in a large cohort of Ugandan children' The Journal of antimicrobial chemotherapy, vol. 74, no. 10, pp. 3035-3043. https://doi.org/10.1093/jac/dkz266

Long-term virological outcomes, failure and acquired resistance in a large cohort of Ugandan children. / Huibers, M. H. W.; Kityo, C.; Boerma, R. S.; Kaudha, E.; Sigaloff, K. C. E.; Balinda, S. N.; Bertagnolio, S.; Nakanjako, R.; Mugyenyi, P.; Calis, J. C. J.; Boele van Hensbroek, M.; Rinke de Wit, T. F.

In: The Journal of antimicrobial chemotherapy, Vol. 74, No. 10, 01.10.2019, p. 3035-3043.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Long-term virological outcomes, failure and acquired resistance in a large cohort of Ugandan children

AU - Huibers, M. H. W.

AU - Kityo, C.

AU - Boerma, R. S.

AU - Kaudha, E.

AU - Sigaloff, K. C. E.

AU - Balinda, S. N.

AU - Bertagnolio, S.

AU - Nakanjako, R.

AU - Mugyenyi, P.

AU - Calis, J. C. J.

AU - Boele van Hensbroek, M.

AU - Rinke de Wit, T. F.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - OBJECTIVES: To evaluate long-term virological failure (VF) and drug resistance among HIV-infected Ugandan children on first-line ART. METHODS: In a multicentre prospective cohort study, viral load (VL) and drug resistance mutations (DRMs) were investigated at baseline and 6 monthly intervals in children (age ≤ 12 years). VF (two consecutive VLs >1000 copies/mL or death after 6 months of ART) was defined as early VF (0-24 months of ART) or late VF (25-48 months of ART). An active regimen was defined as partially active if the genotypic susceptibility score (GSS) was <3. RESULTS: Between 2010 and 2011, 316 children were enrolled. Viral suppression was achieved in 75.8%, 71.5%, 72.6% and 69.2% at 12, 24, 36 and 48 months. VF occurred in 111/286 (38.8%), of which 67.6% was early and 32.4% late VF. Early VF was associated with a partially active regimen at baseline (OR 6.0, 95% CI 1.9-18.5), poor adherence (OR 3.1, 95% CI 1.3-7.4) and immunodeficiency (OR 3.3, 95% CI 1.1-10.2). Late VF was associated with age >3 years (OR 2.5, 95% CI 1.0-6.6) and WHO stage 3/4 (OR 4.2, 95% CI 1.4-13.4). Acquired DRMs were detected in 27.0% before 24 months, versus 14.4% after 24 months (P < 0.001). A total of 92.2% of the children with early VF, versus 56.2% with late VF, had a partially active regimen (P < 0.001). CONCLUSIONS: VF rates were high, occurred predominantly in the first 24 months and appeared to increase again in year four. Risk factors and patterns of early VF/DRMs were different from those of late VF/DRMs. Virological control may improve by close monitoring and prompt switching to second-line therapy in the first 24 months. Late VF may be prevented by early start of ART.

AB - OBJECTIVES: To evaluate long-term virological failure (VF) and drug resistance among HIV-infected Ugandan children on first-line ART. METHODS: In a multicentre prospective cohort study, viral load (VL) and drug resistance mutations (DRMs) were investigated at baseline and 6 monthly intervals in children (age ≤ 12 years). VF (two consecutive VLs >1000 copies/mL or death after 6 months of ART) was defined as early VF (0-24 months of ART) or late VF (25-48 months of ART). An active regimen was defined as partially active if the genotypic susceptibility score (GSS) was <3. RESULTS: Between 2010 and 2011, 316 children were enrolled. Viral suppression was achieved in 75.8%, 71.5%, 72.6% and 69.2% at 12, 24, 36 and 48 months. VF occurred in 111/286 (38.8%), of which 67.6% was early and 32.4% late VF. Early VF was associated with a partially active regimen at baseline (OR 6.0, 95% CI 1.9-18.5), poor adherence (OR 3.1, 95% CI 1.3-7.4) and immunodeficiency (OR 3.3, 95% CI 1.1-10.2). Late VF was associated with age >3 years (OR 2.5, 95% CI 1.0-6.6) and WHO stage 3/4 (OR 4.2, 95% CI 1.4-13.4). Acquired DRMs were detected in 27.0% before 24 months, versus 14.4% after 24 months (P < 0.001). A total of 92.2% of the children with early VF, versus 56.2% with late VF, had a partially active regimen (P < 0.001). CONCLUSIONS: VF rates were high, occurred predominantly in the first 24 months and appeared to increase again in year four. Risk factors and patterns of early VF/DRMs were different from those of late VF/DRMs. Virological control may improve by close monitoring and prompt switching to second-line therapy in the first 24 months. Late VF may be prevented by early start of ART.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31289811

U2 - 10.1093/jac/dkz266

DO - 10.1093/jac/dkz266

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VL - 74

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EP - 3043

JO - The Journal of antimicrobial chemotherapy

JF - The Journal of antimicrobial chemotherapy

SN - 1460-2091

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