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. 2023 May 1;37(6):913-923.
doi: 10.1097/QAD.0000000000003488. Epub 2023 Jan 20.

Impact of sub-optimal HIV viral control on activated T cells

Francesca I F Arrigoni  1   2 , Moira Spyer  1   3 , Patricia Hunter  1 , Dagmar Alber  1 , Cissy Kityo  4 , James Hakim  5 , Allen Matubu  5 , Patrick Olal  4 , Nicholas I Paton  6 , A Sarah Walker  3   4 , Nigel Klein  1 ; the EARNEST trial team
Affiliations

Impact of sub-optimal HIV viral control on activated T cells

Francesca I F Arrigoni et al. AIDS. .

Abstract

Objective: HIV viral load (VL) monitoring is generally conducted 6-12 monthly in low- and middle-income countries, risking relatively prolonged periods of poor viral control. We explored the effects of different levels of loss of viral control on immune reconstitution and activation.

Design: Two hundred and eight participants starting protease inhibitor (PI)-based second-line therapy in the EARNEST trial (ISRCTN37737787) in Uganda and Zimbabwe were enrolled and CD38 + /HLA-DR + immunophenotyping performed (CD8-FITC/CD38-PE/CD3-PerCP/HLA-DR-APC; centrally gated) in real-time at 0, 12, 48, 96 and 144 weeks from randomization.

Methods: VL was assayed retrospectively on samples collected every 12-16 weeks and classified as continuous suppression (<40 copies/ml throughout); suppression with transient blips; low-level rebound (two or more consecutive VL >40, <5000 copies/ml); high-level rebound/nonresponse (two or more consecutive VL >5000 copies/ml).

Results: Immunophenotype reconstitution varied between that defined by numbers of cells and that defined by cell percentages. Furthermore, VL dynamics were associated with substantial differences in expression of CD4 + and CD8 + cell activation markers, with only individuals with high-level rebound/nonresponse (>5000 copies/ml) experiencing significantly greater activation and impaired reconstitution. There was little difference between participants who suppressed consistently and who exhibited transient blips or even low-level rebound by 144 weeks ( P > 0.2 vs. suppressed consistently).

Conclusion: Detectable viral load below the threshold at which WHO guidelines recommend that treatment can be maintained without switching (1000 copies/ml) appear to have at most, small effects on reconstitution and activation, for patients taking a PI-based second-line regimen.

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Figures

Figure 1
Figure 1. Number and proportion of activated CD4 and CD8 cells over time on second-line ART
Note: Showing mean plus 95% confidence interval for each randomised group at each timepoint.
Figure 2
Figure 2. Viral load responses over time on second line therapy
Figure 3
Figure 3
Changes in CD4 and activated CD4 sub-populations over time, expressed both as percentages and normalised to circulating CD4 levels. Note: showing mean plus 95% confidence interval for each group at each timepoint.
Figure 4
Figure 4
CD4/CD38/HLADR expression and viral load, by VL response at baseline (A), 12 weeks (B), 48 weeks (C), 96 weeks (D) and 144 weeks (E) for viral loads >40 copies/ml. Note: Definition of suppressed consistently at 12 weeks includes VL response
Figure 5
Figure 5. Changes in CD8 and activated CD8 sub-populations over time, expressed both as percentages and normalised to circulating CD8 levels.
Note: Showing mean plus 95% confidence interval for each group at each timepoint.
See this image and copyright information in PMC

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