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. 2021 Aug 1;35(10):1537-1548.
doi: 10.1097/QAD.0000000000002916.

The impact of viraemia on inflammatory biomarkers and CD4+ cell subpopulations in HIV-infected children in sub-Saharan Africa

Andrew J Prendergast  1   2 , Alexander J Szubert  2 , Godfrey Pimundu  3 , Chipo Berejena  4 , Pietro Pala  5 , Annie Shonhai  4 , Patricia Hunter  6 , Francesca I F Arrigoni  7 , Victor Musiime  3   8 , Mutsa Bwakura-Dangarembizi  4 , Philippa Musoke  9 , Hannah Poulsom  6 , Macklyn Kihembo  5 , Paula Munderi  6 , Diana M Gibb  2 , Moira J Spyer  2 , A Sarah Walker  2 , Nigel Klein  6 ; and the ARROW Trial Team
Affiliations

The impact of viraemia on inflammatory biomarkers and CD4+ cell subpopulations in HIV-infected children in sub-Saharan Africa

Andrew J Prendergast et al. AIDS. .

Abstract

Objective: To determine the impact of virological control on inflammation and cluster of differentiation 4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa.

Design: Longitudinal cohort study.

Methods: In a sub-study of the ARROW trial (ISRCTN24791884), we measured longitudinal HIV viral loads, inflammatory biomarkers (C-reactive protein, tumour necrosis factor alpha, interleukin 6 (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 viral load or rebound. We used multi-level models to estimate rates of increase or decrease in laboratory markers, and Poisson regression to estimate the incidence of clinical events.

Results: Overall, 42% children experienced viral blips, but these had no significant impact on immune reconstitution or inflammation. Persistent detectable viraemia 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 viraemia who remain at low risk of disease progression.

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Conflict of interest statement

Conflicts of Interest

No authors have any conflicts of interest to declare.

No authors have any commercial or other association that might present a conflict of interest.

Figures

Figure 1
Figure 1. Overall changes in biomarkers and VL on first-line ART.
(a) CD4 and CD8; (b) CD4 subpopulations; (c) IL-7 proliferating and activated CD4 cells; (d) inflammatory biomarkers; and (e) VL.
Figure 2
Figure 2. CD4 and CD8 over time with consistent VL suppression, previous VL blips, pLLVL and rebound
Figure 3
Figure 3. Inflammatory cytokines over time consistent VL suppression, previous VL blips, pLLVL and rebound
See this image and copyright information in PMC

References

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