De La Torre Tarazona Erick, Moraga Elisa, Vaquer Raúl, Sánchez-Palomino Sonsoles, de Lazzari Elisa, Luna Laura, Vicens-Artés Sònia, García Fraile Lucio Jesús, Peraire Joaquim, Garcia-Gasalla Mercedes, Balsalobre Luz, Guillén Martínez Sergio, López Cortés Luis Fernando, Jarrín Inma, Serrano-Villar Sergio, Alcamí José, Moreno Santiago
Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Carretera de Colmenar Km 9,100, 28034, Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
Sci Rep. 2025 Jul 13;15(1):25306. doi: 10.1038/s41598-025-09474-1.
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.
消除潜伏性病毒储存库仍然是寻求治愈艾滋病病毒感染者（PWH）的主要障碍。在开始抗逆转录病毒治疗（ART）时给予潜伏逆转剂（LRA）可能会提高旨在实现艾滋病病毒缓解的策略的有效性。本研究评估了具有艾滋病病毒潜伏逆转特性的抗逆转录病毒药物马拉维罗（MVC）在ART开始时给药对病毒储存库大小的影响。我们对开始接受ART治疗的PWH进行了一项纵向观察性研究，其治疗方案包括含MVC方案（MVC起始组，n = 12）或不含MVC方案（非MVC起始组，n = 22），或在病毒载量（VL）检测不到后改用含MVC方案（MVC转换组，n = 9）。通过Alu-LTR和完整前病毒DNA检测（IPDA）方法确定艾滋病病毒储存库大小，并通过巢式定量聚合酶链反应检测细胞相关艾滋病病毒RNA（ca-HIV-RNA）。比较分析采用混合多变量线性模型。中位随访90周后，与非MVC起始组相比，MVC起始组的整合型和IPDA总型（分别为7.1倍和4.0倍）艾滋病病毒DNA储存库减少幅度更大，但IPDA完整型艾滋病病毒DNA储存库减少幅度不大。与MVC转换组相比，MVC起始组的整合型、IPDA总型和IPDA完整型艾滋病病毒DNA水平降低幅度也更大（从5.4倍到13.8倍）。此外，在MVC起始组和非MVC起始组之间，通过ca-HIV-RNA水平或HIV-RNA/HIV-DNA比值评估的艾滋病病毒转录活性没有显著差异。总之，在可检测到VL阶段开始使用具有艾滋病病毒潜伏逆转活性的药物进行ART治疗，可能有助于更大幅度地减少艾滋病病毒DNA储存库。这些发现可为未来通过“激活并清除”策略实现艾滋病病毒缓解的试验设计提供参考。
