The impact of viraemia on inflammatory biomarkers and CD4 cell subpopulations in HIV-infected children in sub-Saharan Africa
Objective: To determine the impact of virological control on inflammation and CD4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa. Design: Longitudinal cohort study. Methods: In a substudy of the ARROW trial (ISRCTN24791884), we measured longi...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Lippincott, Williams & Wilkins
2021
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| _version_ | 1826307409199497216 |
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| author | Prendergast, AJ Szubert, AJ Pimundu, G Berejena, C Pala, P Shonhai, A Hunter, P Arrigoni, F Musiime, V Bwakura-Dangarembizi, M Musoke, P Poulsom, H Kihembo, M Munderi, P Gibb, DM Spyer, MJ Walker, AS Klein, N |
| author_facet | Prendergast, AJ Szubert, AJ Pimundu, G Berejena, C Pala, P Shonhai, A Hunter, P Arrigoni, F Musiime, V Bwakura-Dangarembizi, M Musoke, P Poulsom, H Kihembo, M Munderi, P Gibb, DM Spyer, MJ Walker, AS Klein, N |
| author_sort | Prendergast, AJ |
| collection | OXFORD |
| description | Objective:
To determine the impact of virological control on inflammation and CD4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa.
Design:
Longitudinal cohort study.
Methods:
In a substudy of the ARROW trial (ISRCTN24791884), we measured longitudinal HIV viral loads, inflammatory biomarkers (CRP, TNF-α, IL-6, soluble CD14), and (Uganda only) whole blood immunophenotype by flow cytometry in 311 Zimbabwean and Ugandan children followed for median 3.5 years on first-line ART. We classified each viral load measurement as consistent suppression, blip/post-blip, persistent low-level VL or rebound. We used multi-level models to estimate rates of increase or decrease in laboratory markers, and Poisson regression to estimate incidence of clinical events.
Results:
Overall, 42% children experienced viral blips, but these had no significant impact on immune reconstitution or inflammation. Persistent detectable viremia occurred in one-third of children and prevented further immune reconstitution, but had little impact on inflammatory biomarkers. Virological rebound to ≥5000 copies/mL was associated with arrested immune reconstitution, rising IL-6 and increased risk of clinical disease progression.
Conclusions:
As viral load testing becomes more available in sub-Saharan Africa, repeat testing algorithms will be required to identify those with virological rebound, who need switching to prevent disease progression, whilst preventing unnecessary second-line regimen initiation in the majority of children with detectable viremia who remain at low risk of disease progression.
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| first_indexed | 2024-03-07T07:02:42Z |
| format | Journal article |
| id | oxford-uuid:13de3092-3c74-46a3-979d-0a5ecfdce8da |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:02:42Z |
| publishDate | 2021 |
| publisher | Lippincott, Williams & Wilkins |
| record_format | dspace |
| spelling | oxford-uuid:13de3092-3c74-46a3-979d-0a5ecfdce8da2022-04-14T07:59:39ZThe impact of viraemia on inflammatory biomarkers and CD4 cell subpopulations in HIV-infected children in sub-Saharan AfricaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:13de3092-3c74-46a3-979d-0a5ecfdce8daEnglishSymplectic ElementsLippincott, Williams & Wilkins2021Prendergast, AJSzubert, AJPimundu, GBerejena, CPala, PShonhai, AHunter, PArrigoni, FMusiime, VBwakura-Dangarembizi, MMusoke, PPoulsom, HKihembo, MMunderi, PGibb, DMSpyer, MJWalker, ASKlein, NObjective: To determine the impact of virological control on inflammation and CD4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa. Design: Longitudinal cohort study. Methods: In a substudy of the ARROW trial (ISRCTN24791884), we measured longitudinal HIV viral loads, inflammatory biomarkers (CRP, TNF-α, IL-6, soluble CD14), and (Uganda only) whole blood immunophenotype by flow cytometry in 311 Zimbabwean and Ugandan children followed for median 3.5 years on first-line ART. We classified each viral load measurement as consistent suppression, blip/post-blip, persistent low-level VL or rebound. We used multi-level models to estimate rates of increase or decrease in laboratory markers, and Poisson regression to estimate incidence of clinical events. Results: Overall, 42% children experienced viral blips, but these had no significant impact on immune reconstitution or inflammation. Persistent detectable viremia occurred in one-third of children and prevented further immune reconstitution, but had little impact on inflammatory biomarkers. Virological rebound to ≥5000 copies/mL was associated with arrested immune reconstitution, rising IL-6 and increased risk of clinical disease progression. Conclusions: As viral load testing becomes more available in sub-Saharan Africa, repeat testing algorithms will be required to identify those with virological rebound, who need switching to prevent disease progression, whilst preventing unnecessary second-line regimen initiation in the majority of children with detectable viremia who remain at low risk of disease progression. |
| spellingShingle | Prendergast, AJ Szubert, AJ Pimundu, G Berejena, C Pala, P Shonhai, A Hunter, P Arrigoni, F Musiime, V Bwakura-Dangarembizi, M Musoke, P Poulsom, H Kihembo, M Munderi, P Gibb, DM Spyer, MJ Walker, AS Klein, N The impact of viraemia on inflammatory biomarkers and CD4 cell subpopulations in HIV-infected children in sub-Saharan Africa |
| title | The impact of viraemia on inflammatory biomarkers and CD4 cell subpopulations in HIV-infected children in sub-Saharan Africa |
| title_full | The impact of viraemia on inflammatory biomarkers and CD4 cell subpopulations in HIV-infected children in sub-Saharan Africa |
| title_fullStr | The impact of viraemia on inflammatory biomarkers and CD4 cell subpopulations in HIV-infected children in sub-Saharan Africa |
| title_full_unstemmed | The impact of viraemia on inflammatory biomarkers and CD4 cell subpopulations in HIV-infected children in sub-Saharan Africa |
| title_short | The impact of viraemia on inflammatory biomarkers and CD4 cell subpopulations in HIV-infected children in sub-Saharan Africa |
| title_sort | impact of viraemia on inflammatory biomarkers and cd4 cell subpopulations in hiv infected children in sub saharan africa |
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