Impact of the initial administration of an antiretroviral drug with latency reversal properties on the HIV reservoir size

The elimination of the latent viral reservoir remains the main barrier in the quest for a cure for people with HIV (PWH). The administration of latency reversal agents (LRA) at antiretroviral treatment (ART) initiation could improve the effectiveness of strategies aimed at HIV remission. This study...

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Detalles Bibliográficos
Autores: Moraga, E., Vaquer, R., Sánchez-Palomino, S., de Lazzari, E., Luna, L., Vicens-Artés, S., García Fraile, L.J., Garcia-Gasalla, M., Balsalobre, L., Guillén Martínez, S., López Cortés, L.F., Serrano-Villar, S., Alcamí, J., Martínez, I., Alonso, J., Gallego, M., Pousada, G., Ocampo, A., Miralles, C., Morano, L., Pérez, A., Poveda, E., González-Serna, A., Corma, A., Real, L.M., Rincón, P., Sánchez, J.M., Torres, R., Martinez-Echevarría, R.R.-R., Caballero, J.M., Corona, D., Pérez, I., Camacho, Á., Frias, M., Machuca, I., López, P., Juárez, A.R., Ruíz, I., Román, A.R., Ferrer, A., Gómez, S.P., Galindo, M.J., Novella, M., Hernández, C., Arranz, A., Sanz, J., Somodevilla, Á., Pascual, J.F., Ruiz, M.P., González-Ruano, P., Malmierca, E., Suarez-García, I., Chiclano, I., Merlos, M.A., Iborra, A., Castillo, A., Albendin, H., Galera, C., Castelo, B., Vázquez, P., Pernas, B., Mena, Á., Guirao, A.J.S., Alcaraz, B., García, J., Vera, F.J., Martinez, L., Martínez, O.J., Prada, J.L., de la Torre, J., del Arco, A., Pérez, J., Olalla, J., Saumoy, M., Imaz, A., Tiraboschi, J.M., Llaves, S., Roca, C., Espinosa, N., López-Cortés, L.F., Palacios, R., Viciana, I., Gómez, C., López, M., Santos, J., Payeras, A., Martin, L., Vilchez, H.H., Homar, F., Murillas, J., Fanjul, F.J., Garcia-Gazalla, M., Campins, A.A., Ribas, M., Peñaranda, M., Riera, M., Orviz, E., Baza, B., Ayerdi, O., Ballesteros, J., Vera, M., Carrió, J.C., Puerta, T., Rodríguez, C., Raposo, M., Del Romero, J., Sánchez, V., Illescas, M., Chaves, L., Peregrina, J., Faro, N., Anguita, F., Ruiz-Sancho, A., Viñuela, L., Guirao, E., Fuentes, A., de Salazar, A., Vinuesa, D., Chueca, N., Álvarez, M., Medina, L.M., Martínez, C., García, F., Hernández, M.D., Martínez, R., Guijarro, E., González, R., García, E., Selva, D., Oliver, E., Tomás, C., Muñoz, Á., Bravo, J., Alcaraz, A., Bernal, E., Ron, R., García, A., Díaz, J., García, C.D., Pedraza, L.M., Moreno, E., De La Torre Tarazona, E., Hermida, J.M., Pérez-Molina, J.A., Sánchez, M., Vallejo, A., Martínez-Sanz, J., Vivancos, M.J., Pérez, M.J., Moreno, A., Dronda, F., Casado, J.L., del Campo, S., Moreno, S., García, M.A., Gutiérrez, Á., Ciudad, M., Sáez, C., Bautista, A., Barrios, A., Calvet, M., Sánchez-Cerrillo, I., Martín, E., de los Santos, A., de los Santos, I., Gisbert, L., Font, R., Martinez-Lacasa, J., Cairó, M., Jaén, A., Martinez, M., Dalmau, D., López, C.O., de Gea Grela, A., del Mar Arcos, M., Valencia, E., Sendagorta, E., Sainz, T., Rodés, B., Ramos-Ruperto, L., Montes, M.L., Montejano, R., de Miguel, R., Micán, R., Mayoral, M., Martín-Carbonero, M.L., González-Baeza, A., Hontañón, V., Herranz, P., Falces, I., Escosa, L., Castro, J.M., Cadiñanos, J., Cano-Smith, J., Busca, C., Bernardino, J.I., Arribas, V., Arribas, J.R., Delgado-Hierro, A., González-García, J., Blanes, R., Fernández, J., Salavert, M., Calabuig, E., Tasias, M., Montero, M., Sánchez, A., Chafino, S., Alba, V., Gómez-Bertomeu, F., García-Pardo, G., Olona, M., Guillem, L., Villar, B., Viladés, C., Martí, A., Rull, A., Peraire, J., Corral, S., Fanciulli, C., Pérez, L., Diez, C., Tejerina, F., Aldamiz-Echevarría, T., Gijón, P., Ramírez, M., Berenguer, J., Gutiérrez, I., de Quirós, J.C.L.B., Andreo, M., Quiles, A., Espinosa, M., López, S., Ledesma, C., Ruiz, M., Gonzalo-Jiménez, N., Vallejo, J., López, L., Ena, N., García-Sánchez, L., Ding, C., de la Rica, A., Carvajal, M., Mascarell, P., Botella, Á., Guillén, L., Telenti, G., Abellán, J.G., Barber, X., García, J.A., Galiana, A., Fernández, M., Pascual, R., Adsuar, A., Padilla, S., Masiá, M., Robledano, C., Gutiérrez, F., Sanz, M.L., Carlos, A.B., Carmona-Torre, F., Gil, L., Álvarez-Rodriguez, I., Kortajarena, X., Ibarguren, M., Azkune, H., Bustinduy, M.J., Goenaga, M.Á., Camino, X., Aramburu, M.J., Torres, J.M., Navarro, R., Santacreu, M., Bermejo, L., Pinto, A., de Lagarde, M., Rial, D., Hernando, M.A., Bisbal, O., Rubio, R., Pulido, F., Díaz-Arias, J., Magadan, R.C., Rivas-Carmenado, M.E., Asensi, V., Rodríguez, D., Bethencourt, A., Romero, L., Hernández, M.I., Pelazas, R., Alonso, M.M., Díaz-Flores, F., García, D., Lirola, A.L., Alemán, M.R., Pinargote, H., Pérez, V., Torrus, D., Boix, V., Reus, S., Giner, L., Rodríguez, J.C., Sánchez-Payá, J., Agea, I., García, G., Merino, E., Portilla, I., Portilla, J., Juárez, R., Gómez-García, T., Marco, C., Izquierdo, R., Rava, M., Moreno, C., Jarrín, I., Muñoz-Fernández, M.Á., González, J., Vidal, F., Iribarren, J.A., Garcia, F., González, M.I., Navarro, M.L.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Málaga
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:dnet:r-fisabio___::87446cf40489dee09ec46163a39eaa21
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/20785
https://www.scopus.com/inward/record.uri?eid=2-s2.0-105011417403&doi=10.1038%2fs41598-025-09474-1&partnerID=40&md5=8e4bea1512a89a59d9f3c3bcec244b1d
Access Level:acceso abierto
Palabra clave:Antiretroviral Therapy
HIV reservoir
Latency reversal agent
Maraviroc
Timing of administration
Adult
Anti-HIV Agents
Anti-Retroviral Agents
Female
HIV Infections
HIV-1
Humans
Longitudinal Studies
Male
Middle Aged
RNA, Viral
Viral Load
Virus Latency
anti human immunodeficiency virus agent
antiretrovirus agent
maraviroc
virus RNA
adult
drug effect
drug therapy
female
genetics
human
Human immunodeficiency virus 1
Human immunodeficiency virus infection
longitudinal study
male
middle aged
physiology
virology
virus latency
virus load
Descripción
Sumario:The elimination of the latent viral reservoir remains the main barrier in the quest for a cure for people with HIV (PWH). The administration of latency reversal agents (LRA) at antiretroviral treatment (ART) initiation could improve the effectiveness of strategies aimed at HIV remission. This study assessed the impact of maraviroc (MVC), an antiretroviral drug with HIV latency reversal properties, on the viral reservoir size when it is administered at ART initiation. We conducted a longitudinal observational study in PWH initiating ART with a regimen including (MVC-initiation, n = 12) or not including MVC (non-MVC-initiation, n = 22), or switching to an MVC-containing regimen after achieving an undetectable viral load (VL) (MVC-switch, n = 9). The HIV reservoir size was determined via Alu-LTR and Intact Proviral DNA Assay (IPDA) methods, and cell-associated HIV-RNA (ca-HIV-RNA) by nested-qPCR. Comparative analyses employed mixed multivariate linear models. After a median of 90 weeks, the MVC-initiation group showed a greater reduction in integrated and IPDA-total (7.1- and 4.0-fold, respectively), but not IPDA-intact, HIV-DNA reservoir compared to the non-MVC-initiation group. The reductions in integrated, IPDA-total, and IPDA-intact HIV-DNA levels in the MVC-initiation group were also greater compared to the MVC-switch group (from 5.4 to 13.8-fold). Moreover, no significant differences in the HIV transcriptional activity, assessed by ca-HIV-RNA levels or HIV-RNA/HIV-DNA ratios, were observed between the MVC-initiation and non-MVC-initiation groups. In conclusion, starting ART with a drug with HIV latency reversing activity at detectable VL phase may contribute to a greater reduction in the HIV-DNA reservoir. These findings could inform the design of future trials targeting HIV remission via a “kick and kill” strategy. © The Author(s) 2025.

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