Switching from a protease inhibitor-based regimen to a dolutegravir-based regimen: a randomized clinical trial to determine the effect on peripheral blood and ileum biopsies from ART-suppressed HIV-infected individuals

BACKGROUND: Optimization of combination antiretroviral therapy (cART) can impact the human immunodeficiency virus (HIV) reservoir. We evaluated the effect on the HIV reservoir in peripheral blood and ileum biopsies in patients switching from boosted protease inhibitor (PI/r)-based therapy to doluteg...

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Detalles Bibliográficos
Autores: Moron-Lopez, S., Navarro, J., Jimenez, M., Rutsaert, S., Urrea, V., Puertas, M. C., Torrella, A., Clercq, L., Ribas, B. P., Galvez, C., Salgado, M., Vandekerckhove, L., Blanco, J., CRESPO CASAL, MANUEL, Martinez-Picado, J.
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/16008
Acceso en línea:https://www.ncbi.nlm.nih.gov/pubmed/30590412
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763634/pdf/ciy1095.pdf
http://hdl.handle.net/20.500.11940/16008
Access Level:acceso abierto
Palabra clave:HIV Integrase Inhibitors
Middle Aged
Ileum
Anti-Retroviral Agents
Biopsy
Pyridones
HIV
HIV Protease Inhibitors
Heterocyclic Compounds
Humans
Piperazines
Oxazines
HIV Infections
Virus Replication
Viremia
VIH
oxacinas
replicación viral
biopsia
mediana edad
viremia
infecciones por VIH
piridonas
piperacinas
íleon
inhibidores de la proteasa del VIH
humanos
inhibidores de la integrasa del VIH
antirretrovirales
compuestos heterocíclicos
CHUVI
Descripción
Sumario:BACKGROUND: Optimization of combination antiretroviral therapy (cART) can impact the human immunodeficiency virus (HIV) reservoir. We evaluated the effect on the HIV reservoir in peripheral blood and ileum biopsies in patients switching from boosted protease inhibitor (PI/r)-based therapy to dolutegravir (DTG)-based therapy. METHODS: Impact of Integrase-inhibitor DOlutegravir On the viral Reservoir (INDOOR) is a phase 4 open-label clinical trial that randomly included 42 HIV type 1-infected individuals on effective cART: 20 who switched from PI/r-based to DTG-based cART (switch group), and 22 who remained in PI/r-based regimens (control group). We analyzed blood and ileum biopsies to quantify episomal, total, and integrated HIV DNA, cell-associated HIV RNA, residual plasma viremia, T-cell subsets, cell activation, and inflammation markers. RESULTS: There were no related adverse events or treatment discontinuations due to drug intolerance. The HIV reservoir was consistently larger in ileal than in peripheral CD4+ T cells in both groups (P < .01). Residual viremia in plasma decreased in the switch group (P = .03). However, we did not observe significant longitudinal changes in low-level viral replication, total and integrated HIV reservoir, HIV transcription, T-cell maturation subsets, immunoactivation markers, inflammatory soluble proteins, or cellular markers of latently infected cells. CONCLUSIONS: The INDOOR study is the first evaluation of changes in HIV reservoir size in ileum biopsies and in peripheral blood in individuals switched from PI/r- to DTG-based cART. Although this switch was safe and well tolerated, it had no impact on a large array of immunological and inflammatory markers or on HIV reservoir markers in peripheral or in ileal CD4+ T cells. CLINICAL TRIALS REGISTRATION: EudraCT 2014-004331-39.

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