Cardioprotective effects of early versus late initiated antiretroviral treatment in adolescents with perinatal HIV-1 infection

Itai M. Magodoro; Carlos E. Guerrero-Chalela; Brian Claggett; Stephen Jermy; Petronella Samuels; Landon Myer; Heather J. Zar; Jennifer Jao; Mpiko Ntsekhe; Mark J. Siedner; Ntobeko A.B. Ntusi

doi:10.1038/s41598-024-65119-9

Cardioprotective effects of early versus late initiated antiretroviral treatment in adolescents with perinatal HIV-1 infection

Itai M. Magodoro^*, Carlos E. Guerrero-Chalela, Brian Claggett, Stephen Jermy, Petronella Samuels, Landon Myer, Heather J. Zar, Jennifer Jao, Mpiko Ntsekhe, Mark J. Siedner, Ntobeko A.B. Ntusi^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

Abstract

Whether, and how, cardioprotective effects of antiretroviral treatment (ART) in adolescents with perinatal HIV infection (APHIV) vary with age at treatment initiation is unknown. We used magnetic resonance imaging to compare cardiac status between APHIV initiated on ART at < 5 years of age (early ART, n = 37) and ≥ 5 years of age (delayed ART, n = 34) versus HIV-uninfected peers (n = 21), reporting z-score mean differences adjusted for confounders. Relative to HIV-uninfected adolescents, APHIV with early ART had higher left ventricular (LV) global circumferential strain (GCS) [adjusted mean (95%CI) z-score: 0.53 (0.13, 0.92)] and maximum indexed left atrium volume (LAVi) [adjusted z-score: 0.55 (0.08, 1.02)]. In contrast, APHIV with delayed ART had greater indexed LV end-diastolic volume (LVEDVi) [adjusted z-score: 0.47 (0.09, 0.86)] and extracellular volume fraction [adjusted z-score: 0.79 (0.20, 1.37)], but lower GCS [adjusted z-score: −0.51 (−0.91, −0.10)] than HIV-uninfected peers. APHIV had distinct albeit subclinical cardiac phenotypes depending on ART initiation age. Changes in early ART suggested comparatively worse diastology with preserved systolic function while delayed ART was associated with comparatively increased diffuse fibrosis and LV dilatation with reduced systolic function. The long-term clinical significance of these changes remains to be determined.

Original language	English (US)
Article number	14234
Journal	Scientific reports
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41598-024-65119-9
State	Published - Dec 2024

Funding

Itai Magodoro was supported by a training award from the Fogarty International Center and National Institute of Mental Health of the National Institutes of Health (D43 TW010543) and the AIDS Healthcare Foundation, Los Angeles, USA. Heather Zar is supported by the South African Medical Research Council (SA MRC). CTAAC was funded by the NIH (R01HD074051; PI Heather Zar). Ntobeko Ntusi gratefully acknowledges funding from the National Research Foundation, South African Medical Research Council, US National Institutes of Health, Medical Research Council (UK), and the Lily and Ernst Hausmann Trust.

Keywords

ART initiation
Adolescence
CMR
Cardio-protection
PHIV

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41598-024-65119-9

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Magodoro, I. M., Guerrero-Chalela, C. E., Claggett, B., Jermy, S., Samuels, P., Myer, L., Zar, H. J., Jao, J., Ntsekhe, M., Siedner, M. J., & Ntusi, N. A. B. (2024). Cardioprotective effects of early versus late initiated antiretroviral treatment in adolescents with perinatal HIV-1 infection. Scientific reports, 14(1), Article 14234. https://doi.org/10.1038/s41598-024-65119-9

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abstract = "Whether, and how, cardioprotective effects of antiretroviral treatment (ART) in adolescents with perinatal HIV infection (APHIV) vary with age at treatment initiation is unknown. We used magnetic resonance imaging to compare cardiac status between APHIV initiated on ART at < 5 years of age (early ART, n = 37) and ≥ 5 years of age (delayed ART, n = 34) versus HIV-uninfected peers (n = 21), reporting z-score mean differences adjusted for confounders. Relative to HIV-uninfected adolescents, APHIV with early ART had higher left ventricular (LV) global circumferential strain (GCS) [adjusted mean (95%CI) z-score: 0.53 (0.13, 0.92)] and maximum indexed left atrium volume (LAVi) [adjusted z-score: 0.55 (0.08, 1.02)]. In contrast, APHIV with delayed ART had greater indexed LV end-diastolic volume (LVEDVi) [adjusted z-score: 0.47 (0.09, 0.86)] and extracellular volume fraction [adjusted z-score: 0.79 (0.20, 1.37)], but lower GCS [adjusted z-score: −0.51 (−0.91, −0.10)] than HIV-uninfected peers. APHIV had distinct albeit subclinical cardiac phenotypes depending on ART initiation age. Changes in early ART suggested comparatively worse diastology with preserved systolic function while delayed ART was associated with comparatively increased diffuse fibrosis and LV dilatation with reduced systolic function. The long-term clinical significance of these changes remains to be determined.",

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AU - Magodoro, Itai M.

AU - Guerrero-Chalela, Carlos E.

AU - Claggett, Brian

AU - Jermy, Stephen

AU - Samuels, Petronella

AU - Myer, Landon

AU - Zar, Heather J.

AU - Jao, Jennifer

AU - Ntsekhe, Mpiko

AU - Siedner, Mark J.

AU - Ntusi, Ntobeko A.B.

PY - 2024/12

Y1 - 2024/12

N2 - Whether, and how, cardioprotective effects of antiretroviral treatment (ART) in adolescents with perinatal HIV infection (APHIV) vary with age at treatment initiation is unknown. We used magnetic resonance imaging to compare cardiac status between APHIV initiated on ART at < 5 years of age (early ART, n = 37) and ≥ 5 years of age (delayed ART, n = 34) versus HIV-uninfected peers (n = 21), reporting z-score mean differences adjusted for confounders. Relative to HIV-uninfected adolescents, APHIV with early ART had higher left ventricular (LV) global circumferential strain (GCS) [adjusted mean (95%CI) z-score: 0.53 (0.13, 0.92)] and maximum indexed left atrium volume (LAVi) [adjusted z-score: 0.55 (0.08, 1.02)]. In contrast, APHIV with delayed ART had greater indexed LV end-diastolic volume (LVEDVi) [adjusted z-score: 0.47 (0.09, 0.86)] and extracellular volume fraction [adjusted z-score: 0.79 (0.20, 1.37)], but lower GCS [adjusted z-score: −0.51 (−0.91, −0.10)] than HIV-uninfected peers. APHIV had distinct albeit subclinical cardiac phenotypes depending on ART initiation age. Changes in early ART suggested comparatively worse diastology with preserved systolic function while delayed ART was associated with comparatively increased diffuse fibrosis and LV dilatation with reduced systolic function. The long-term clinical significance of these changes remains to be determined.

AB - Whether, and how, cardioprotective effects of antiretroviral treatment (ART) in adolescents with perinatal HIV infection (APHIV) vary with age at treatment initiation is unknown. We used magnetic resonance imaging to compare cardiac status between APHIV initiated on ART at < 5 years of age (early ART, n = 37) and ≥ 5 years of age (delayed ART, n = 34) versus HIV-uninfected peers (n = 21), reporting z-score mean differences adjusted for confounders. Relative to HIV-uninfected adolescents, APHIV with early ART had higher left ventricular (LV) global circumferential strain (GCS) [adjusted mean (95%CI) z-score: 0.53 (0.13, 0.92)] and maximum indexed left atrium volume (LAVi) [adjusted z-score: 0.55 (0.08, 1.02)]. In contrast, APHIV with delayed ART had greater indexed LV end-diastolic volume (LVEDVi) [adjusted z-score: 0.47 (0.09, 0.86)] and extracellular volume fraction [adjusted z-score: 0.79 (0.20, 1.37)], but lower GCS [adjusted z-score: −0.51 (−0.91, −0.10)] than HIV-uninfected peers. APHIV had distinct albeit subclinical cardiac phenotypes depending on ART initiation age. Changes in early ART suggested comparatively worse diastology with preserved systolic function while delayed ART was associated with comparatively increased diffuse fibrosis and LV dilatation with reduced systolic function. The long-term clinical significance of these changes remains to be determined.

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KW - Adolescence

KW - CMR

KW - Cardio-protection

KW - PHIV

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Cardioprotective effects of early versus late initiated antiretroviral treatment in adolescents with perinatal HIV-1 infection

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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