Assessing advances in three decades of clinical antiretroviral therapy on the HIV-1 reservoir
González-Navarro, Irene (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Urrea, Víctor (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Gálvez, Cristina (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
García Guerrero, María del Carmen (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Moron-Lopez, Sara (Institut Germans Trias i Pujol)
Puertas, Maria C. (Institut Germans Trias i Pujol)
Grau, Eulàlia (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Mothe, Beatriz (Institut Germans Trias i Pujol)
Bailón, Lucía (Universitat Autònoma de Barcelona. Departament de Medicina)
Miranda, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
García, Felipe (Universitat de Barcelona)
Leal, Lorna (Universitat de Barcelona)
Vandekerckhove, Linos (Ghent University Hospital (Gant, Bèlgica))
Marconi, Vincent C. (Emory University (Atlanta, Estats Units d'Amèrica))
Sekaly, Rafick P. (Emory University (Atlanta, Estats Units d'Amèrica))
Clotet Sala, Bonaventura (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Martínez Picado, Francisco Javier (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Salgado, Maria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)

Fecha:	2024
Resumen:	Antiretroviral therapy (ART) has improved the clinical management of HIV-1 infection. However, little is known about how the latest ART recommendations affect the heterogeneity of the HIV-1 reservoir size. We used a complete statistical approach to outline parameters underlying the diversity in HIV-1 reservoir size in a cohort of 892 people with HIV-1 (PWH) on suppressive ART for more than 3 years. Total HIV-1-DNA levels were measured in PBMCs using digital droplet PCR (ddPCR). We classified 179 (20%) participants as being low viral reservoir treated (LoViReT) (<50 HIV-1-DNA copies/10 6 PBMCs). Twenty variables were collected to explore their association with the LoViReT phenotype using machine learning approaches. LoViReT status was closely associated with higher nadir CD4, lower zenith pre-ART viral load, lower CD4 recovery, shorter time from diagnosis to undetectable viral load, and initiation of treatment with an integrase inhibitor-containing (InSTI-containing) regimen. Initiation of ART with any InSTI was also linked with a shorter time to undetectable viremia. Locally estimated scatterplot smoothing (LOESS) regression revealed a progressive reduction in the size of the HIV-1 reservoir in individuals who started ART after 2007. Similarly, a higher nadir CD4 and a shorter time to undetectable viremia were observed when treatment was initiated after that year. Our findings demonstrate that the progressive implementation of earlier, universal treatment at diagnosis and the use of InSTIs affected the size of the HIV-1 reservoir. Our work shows that effective management of infection is the first step toward reducing the reservoir and brings us closer to achieving a cure. NIH; Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID), NIH; Merck Sharp & Dohme. In this manuscript, we show that the progressive implementation of earlier, universal treatment at diagnosis and the use of InSTIs affect the size of the HIV-1 reservoir in the population of PWH.
Ayudas:	Agencia Estatal de Investigación PID2020-115931RA-I00 Agencia Estatal de Investigación PID2022-139271OB-I00
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	AIDS/HIV ; Virology ; Drug therapy ; Medical statistics ; Molecular pathology
Publicado en:	The journal of clinical investigation, Vol. 135 (november 2024) , ISSN 1558-8238

DOI: 10.1172/JCI183952
PMID: 39610346

11 p, 2.5 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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