Impact of sub-optimal HIV viral control on activated T-cells: an earnest sub study
<p><strong>Objective:</strong> 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...
| Main Authors: | , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
Wolters Kluwer Health
2023
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| _version_ | 1797112107233181696 |
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| author | Arrigoni, FIF Spyer, M Hunter, P Alber, D Kityo, C Hakim, J Matubu, A Olal, P Paton, NI Walker, AS Klein, N |
| author2 | EARNEST trial team |
| author_facet | EARNEST trial team Arrigoni, FIF Spyer, M Hunter, P Alber, D Kityo, C Hakim, J Matubu, A Olal, P Paton, NI Walker, AS Klein, N |
| author_sort | Arrigoni, FIF |
| collection | OXFORD |
| description | <p><strong>Objective:</strong> 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.</p>
<p><strong>Design:</strong> 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<sup>+</sup>/HLA-DR<sup>+</sup> 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.</p>
<p><strong>Methods:</strong> 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).</p>
<p><strong>Results:</strong> 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<sup>+</sup> and CD8<sup>+</sup> 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 (<em>P</em> > 0.2 vs. suppressed consistently).</p>
<p><strong>Conclusion:</strong> 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.</p> |
| first_indexed | 2024-03-07T08:19:32Z |
| format | Journal article |
| id | oxford-uuid:0251419e-d6d0-4492-a661-861fa23ded25 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:19:32Z |
| publishDate | 2023 |
| publisher | Wolters Kluwer Health |
| record_format | dspace |
| spelling | oxford-uuid:0251419e-d6d0-4492-a661-861fa23ded252024-01-23T07:02:35ZImpact of sub-optimal HIV viral control on activated T-cells: an earnest sub studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0251419e-d6d0-4492-a661-861fa23ded25EnglishSymplectic ElementsWolters Kluwer Health2023Arrigoni, FIFSpyer, MHunter, PAlber, DKityo, CHakim, JMatubu, AOlal, PPaton, NIWalker, ASKlein, NEARNEST trial team<p><strong>Objective:</strong> 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.</p> <p><strong>Design:</strong> 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<sup>+</sup>/HLA-DR<sup>+</sup> 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.</p> <p><strong>Methods:</strong> 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).</p> <p><strong>Results:</strong> 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<sup>+</sup> and CD8<sup>+</sup> 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 (<em>P</em> > 0.2 vs. suppressed consistently).</p> <p><strong>Conclusion:</strong> 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.</p> |
| spellingShingle | Arrigoni, FIF Spyer, M Hunter, P Alber, D Kityo, C Hakim, J Matubu, A Olal, P Paton, NI Walker, AS Klein, N Impact of sub-optimal HIV viral control on activated T-cells: an earnest sub study |
| title | Impact of sub-optimal HIV viral control on activated T-cells: an earnest sub study |
| title_full | Impact of sub-optimal HIV viral control on activated T-cells: an earnest sub study |
| title_fullStr | Impact of sub-optimal HIV viral control on activated T-cells: an earnest sub study |
| title_full_unstemmed | Impact of sub-optimal HIV viral control on activated T-cells: an earnest sub study |
| title_short | Impact of sub-optimal HIV viral control on activated T-cells: an earnest sub study |
| title_sort | impact of sub optimal hiv viral control on activated t cells an earnest sub study |
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