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Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts

BACKGROUND: High HIV-1 DNA levels in peripheral blood mononuclear cells (PBMC) were associated with a higher risk of severe morbidity and a faster decline in CD4 count in ART-naive patients. We report the association between HIV-1 DNA and mortality in HIV-infected adults in a trial of early ART in W...

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Autores principales: N'takpe, Jean Baptiste, Gabillard, Delphine, Moh, Raoul, Gardiennet, Elise, Emieme, Arlette, Badje, Anani, Kouame, Gérard M., Toni, Thomas-d'Aquin, Karcher, Sophie, Carrou, Jérome Le, Ménan, Hervé, Danel, Christine, Eholie, Serge P., Rouzioux, Christine, Anglaret, Xavier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276518/
https://www.ncbi.nlm.nih.gov/pubmed/32512517
http://dx.doi.org/10.1016/j.ebiom.2020.102815
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author N'takpe, Jean Baptiste
Gabillard, Delphine
Moh, Raoul
Gardiennet, Elise
Emieme, Arlette
Badje, Anani
Kouame, Gérard M.
Toni, Thomas-d'Aquin
Karcher, Sophie
Carrou, Jérome Le
Ménan, Hervé
Danel, Christine
Eholie, Serge P.
Rouzioux, Christine
Anglaret, Xavier
author_facet N'takpe, Jean Baptiste
Gabillard, Delphine
Moh, Raoul
Gardiennet, Elise
Emieme, Arlette
Badje, Anani
Kouame, Gérard M.
Toni, Thomas-d'Aquin
Karcher, Sophie
Carrou, Jérome Le
Ménan, Hervé
Danel, Christine
Eholie, Serge P.
Rouzioux, Christine
Anglaret, Xavier
author_sort N'takpe, Jean Baptiste
collection PubMed
description BACKGROUND: High HIV-1 DNA levels in peripheral blood mononuclear cells (PBMC) were associated with a higher risk of severe morbidity and a faster decline in CD4 count in ART-naive patients. We report the association between HIV-1 DNA and mortality in HIV-infected adults in a trial of early ART in West Africa. METHODS: In the Temprano trial, HIV-infected adults were randomly assigned to start ART immediately or defer ART. After trial termination, HIV-1 DNA was measured in whole blood samples frozen at baseline. We analyzed the association between baseline PBMC HIV-1 DNA and long-term mortality. FINDINGS: 2019 patients were followed for 9253 patient-years (median 4.9 years). At baseline, the median CD4 count was 462/mm(3) [IQR 368–571], the median plasma HIV-1 RNA 4.7 log(10) copies/ml [IQR 4.0–5.2], and the median HIV-1 DNA 2.9 log(10) copies/million PBMC [IQR 2.5–3.3]. During follow-up, 86 participants died. In univariate analysis, the hazard ratio [HR] of death was 2.67 (95% CI, 1.68–4.22) for patients with HIV-1 DNA ≥3 log(10) copies/million PBMC vs. others, and 2.10 (95% CI, 1.38–3.21) for patients with HIV-1 RNA ≥5 log10 copies/ml vs. others. In multivariate Cox regression analysis, HIV-1 DNA levels ≥3 log(10) copies/million PBMC were strongly associated mortality (adjusted HR = 2.09, 95% CI 1.24–3.52, p= 0.005) while the association between baseline plasma HIV-1 RNA and mortality was not significant. INTERPRETATION: In these African adults who started ART with high CD4 counts, HIV-1 DNA was a strong independent predictor of death. The HIV reservoir still plays a prognostic role in the early ART era. FUNDING: This trial was supported by the French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, 12224 and 12253)
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spelling pubmed-72765182020-06-10 Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts N'takpe, Jean Baptiste Gabillard, Delphine Moh, Raoul Gardiennet, Elise Emieme, Arlette Badje, Anani Kouame, Gérard M. Toni, Thomas-d'Aquin Karcher, Sophie Carrou, Jérome Le Ménan, Hervé Danel, Christine Eholie, Serge P. Rouzioux, Christine Anglaret, Xavier EBioMedicine Research paper BACKGROUND: High HIV-1 DNA levels in peripheral blood mononuclear cells (PBMC) were associated with a higher risk of severe morbidity and a faster decline in CD4 count in ART-naive patients. We report the association between HIV-1 DNA and mortality in HIV-infected adults in a trial of early ART in West Africa. METHODS: In the Temprano trial, HIV-infected adults were randomly assigned to start ART immediately or defer ART. After trial termination, HIV-1 DNA was measured in whole blood samples frozen at baseline. We analyzed the association between baseline PBMC HIV-1 DNA and long-term mortality. FINDINGS: 2019 patients were followed for 9253 patient-years (median 4.9 years). At baseline, the median CD4 count was 462/mm(3) [IQR 368–571], the median plasma HIV-1 RNA 4.7 log(10) copies/ml [IQR 4.0–5.2], and the median HIV-1 DNA 2.9 log(10) copies/million PBMC [IQR 2.5–3.3]. During follow-up, 86 participants died. In univariate analysis, the hazard ratio [HR] of death was 2.67 (95% CI, 1.68–4.22) for patients with HIV-1 DNA ≥3 log(10) copies/million PBMC vs. others, and 2.10 (95% CI, 1.38–3.21) for patients with HIV-1 RNA ≥5 log10 copies/ml vs. others. In multivariate Cox regression analysis, HIV-1 DNA levels ≥3 log(10) copies/million PBMC were strongly associated mortality (adjusted HR = 2.09, 95% CI 1.24–3.52, p= 0.005) while the association between baseline plasma HIV-1 RNA and mortality was not significant. INTERPRETATION: In these African adults who started ART with high CD4 counts, HIV-1 DNA was a strong independent predictor of death. The HIV reservoir still plays a prognostic role in the early ART era. FUNDING: This trial was supported by the French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, 12224 and 12253) Elsevier 2020-06-05 /pmc/articles/PMC7276518/ /pubmed/32512517 http://dx.doi.org/10.1016/j.ebiom.2020.102815 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
N'takpe, Jean Baptiste
Gabillard, Delphine
Moh, Raoul
Gardiennet, Elise
Emieme, Arlette
Badje, Anani
Kouame, Gérard M.
Toni, Thomas-d'Aquin
Karcher, Sophie
Carrou, Jérome Le
Ménan, Hervé
Danel, Christine
Eholie, Serge P.
Rouzioux, Christine
Anglaret, Xavier
Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts
title Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts
title_full Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts
title_fullStr Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts
title_full_unstemmed Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts
title_short Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts
title_sort association between cellular hiv-1 dna level and mortality in hiv-1 infected african adults starting art with high cd4 counts
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276518/
https://www.ncbi.nlm.nih.gov/pubmed/32512517
http://dx.doi.org/10.1016/j.ebiom.2020.102815
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