Impact of the initial administration of an antiretroviral drug with latency reversal properties on the HIV reservoir size
Abstract 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. Th...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-09474-1 |
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| author | Erick De La Torre Tarazona Elisa Moraga Raúl Vaquer Sonsoles Sánchez-Palomino Elisa de Lazzari Laura Luna Sònia Vicens-Artés Lucio Jesús García Fraile Joaquim Peraire Mercedes Garcia-Gasalla Luz Balsalobre Sergio Guillén Martínez Luis Fernando López Cortés Inma Jarrín Sergio Serrano-Villar José Alcamí Santiago Moreno CoRIS Cohort |
| author_facet | Erick De La Torre Tarazona Elisa Moraga Raúl Vaquer Sonsoles Sánchez-Palomino Elisa de Lazzari Laura Luna Sònia Vicens-Artés Lucio Jesús García Fraile Joaquim Peraire Mercedes Garcia-Gasalla Luz Balsalobre Sergio Guillén Martínez Luis Fernando López Cortés Inma Jarrín Sergio Serrano-Villar José Alcamí Santiago Moreno CoRIS Cohort |
| author_sort | Erick De La Torre Tarazona |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-5aa2e7bdea344ebca035ed54d5775989 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-5aa2e7bdea344ebca035ed54d57759892025-08-20T04:02:46ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-09474-1Impact of the initial administration of an antiretroviral drug with latency reversal properties on the HIV reservoir sizeErick De La Torre Tarazona0Elisa Moraga1Raúl Vaquer2Sonsoles Sánchez-Palomino3Elisa de Lazzari4Laura Luna5Sònia Vicens-Artés6Lucio Jesús García Fraile7Joaquim Peraire8Mercedes Garcia-Gasalla9Luz Balsalobre10Sergio Guillén Martínez11Luis Fernando López Cortés12Inma Jarrín13Sergio Serrano-Villar14José Alcamí15Santiago Moreno16CoRIS CohortInfectious Diseases Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)HIV Unit, Infectious Diseases Service, Hospital Clinic, IDIBAPS, AIDS and HIV Research Group, , University of BarcelonaInfectious Diseases Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos IIICentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos IIIInfectious Diseases Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)HIV Unit, Infectious Diseases Service, Hospital Clinic, IDIBAPS, AIDS and HIV Research Group, , University of BarcelonaCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos IIICentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos IIIHospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa)Hospital Universitario Infanta SofíaInternal Medicine Service, Hospital General Universitario Santa LucíaClinical Unit of Infectious Diseases, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital, University of SevilleCentro Nacional de Epidemiología, Instituto de Salud Carlos IIIInfectious Diseases Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos IIIInfectious Diseases Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Abstract 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.https://doi.org/10.1038/s41598-025-09474-1Latency reversal agentTiming of administrationHIV reservoirMaravirocAntiretroviral Therapy |
| spellingShingle | Erick De La Torre Tarazona Elisa Moraga Raúl Vaquer Sonsoles Sánchez-Palomino Elisa de Lazzari Laura Luna Sònia Vicens-Artés Lucio Jesús García Fraile Joaquim Peraire Mercedes Garcia-Gasalla Luz Balsalobre Sergio Guillén Martínez Luis Fernando López Cortés Inma Jarrín Sergio Serrano-Villar José Alcamí Santiago Moreno CoRIS Cohort Impact of the initial administration of an antiretroviral drug with latency reversal properties on the HIV reservoir size Scientific Reports Latency reversal agent Timing of administration HIV reservoir Maraviroc Antiretroviral Therapy |
| title | Impact of the initial administration of an antiretroviral drug with latency reversal properties on the HIV reservoir size |
| title_full | Impact of the initial administration of an antiretroviral drug with latency reversal properties on the HIV reservoir size |
| title_fullStr | Impact of the initial administration of an antiretroviral drug with latency reversal properties on the HIV reservoir size |
| title_full_unstemmed | Impact of the initial administration of an antiretroviral drug with latency reversal properties on the HIV reservoir size |
| title_short | Impact of the initial administration of an antiretroviral drug with latency reversal properties on the HIV reservoir size |
| title_sort | impact of the initial administration of an antiretroviral drug with latency reversal properties on the hiv reservoir size |
| topic | Latency reversal agent Timing of administration HIV reservoir Maraviroc Antiretroviral Therapy |
| url | https://doi.org/10.1038/s41598-025-09474-1 |
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