Troya Jesús, Pedrero-Tomé Roberto, Buzón Luis, Dueñas Carlos
Department of Internal Medicine, Infanta Leonor University Hospital, 28031 Madrid, Spain.
Infanta Leonor University Hospital Research and Innovation Foundation, 28031 Madrid, Spain.
J Clin Med. 2023 Feb 1;12(3):1176. doi: 10.3390/jcm12031176.
Immune recovery in people living with HIV (PLWHIV) is a residual aspect of antiretroviral treatment (ART) in most patients, but in a non-negligible proportion of them, the CD4+ lymphocytes count, or CD4/CD8 ratio remains suboptimal.
We performed a model of the immune response after 24 weeks of switching to a 2DR with DTG plus 3TC in a retrospective multicenter cohort of undetectable and experienced patients using significant predictor variables associated with the parameters or situations defined as success and failure. Clinical variables studied were CD4+ and CD8+ lymphocyte count, percentage of CD4, and CD4/CD8 ratio. These parameters were assessed at baseline and 24 weeks after the switch. Based on the evolution of each variable, four categories of immune response and four categories of non-immune response were defined. Immune response was defined as CD4+ count > 500 cells/mm, %CD4 > 30%, CD8+ count < 1000 cells/mm and CD4/CD8 ratio ≥ 0.9. Non-response is just the opposite.
In our different models of immunological response, the presence of stage of AIDS ( = 0.035, = 0.065) and current age over 50 years ( = 0.045) are postulated as statistically significative limiting factors in achieving an improvement in CD4, %CD4, CD8, and CD4/CD8 ratio. Late HIV diagnosis ( = 0.156), without statistical significance, enhanced late the previous variables. In contrast, conditions where patients start with CD4 > 500 cells/mm ( = 0.054); CD4 > 30% ( = 0.054, = 0.084); CD8 < 1000 cells/mm ( = 0.018), and CD4/CD8 ≥ 0.9 ( = 0.013, = 0.09) are detected as stimulating or conducive to DTG plus 3TC treatment success.
These models represent a proof of concept that could become a valuable tool for clinicians to predict the effects of DTG plus 3TC on immunological responses prior to the switch in undetectable pre-treated PLWHIV with immune dysfunction. The main predictors for immunological failure were late HIV diagnosis, stage of AIDS, and current age over 50 years. In contrast, starting with a normalized immune status was detected as stimulating or conducive to DTG plus 3TC treatment success.
在大多数接受抗逆转录病毒治疗（ART）的艾滋病毒感染者（PLWHIV）中，免疫恢复是治疗的一个遗留问题，但仍有不可忽视的一部分患者，其CD4 +淋巴细胞计数或CD4/CD8比值仍未达到最佳水平。
在一个回顾性多中心队列中，我们对已接受治疗且病毒载量不可检测的患者，使用与定义为成功和失败的参数或情况相关的显著预测变量，建立了一个在改用由多替拉韦（DTG）加替诺福韦丙酚替诺福韦片（3TC）组成的双药方案（2DR）24周后的免疫反应模型。研究的临床变量包括CD4 +和CD8 +淋巴细胞计数、CD4百分比以及CD4/CD8比值。这些参数在基线时以及换药后24周进行评估。根据每个变量的变化，定义了四类免疫反应和四类非免疫反应。免疫反应定义为CD4 +计数>500个细胞/mm³、CD4百分比>30%、CD8 +计数<1000个细胞/mm³且CD4/CD8比值≥0.9。无反应则情况相反。
在我们不同的免疫反应模型中，艾滋病期的存在（P = 0.035，P = 0.065）和当前年龄超过50岁（P = 0.045）被假定为在改善CD4、CD4百分比、CD8以及CD4/CD8比值方面具有统计学意义的限制因素。艾滋病毒诊断较晚（P = 0.156），虽无统计学意义，但强化了上述变量的影响。相比之下，患者起始时CD4>500个细胞/mm³（P = 0.054）；CD4>30%（P = 0.054，P = 0.084）；CD8<1000个细胞/mm³（P = 0.018）以及CD4/CD8≥0.9（P = 0.013，P = 0.09）被检测为对DTG加3TC治疗成功具有刺激或促进作用。
这些模型代表了一种概念验证，可能成为临床医生在对病毒载量不可检测且存在免疫功能障碍的接受过治疗的PLWHIV进行换药前预测DTG加3TC对免疫反应影响的有价值工具。免疫失败的主要预测因素是艾滋病毒诊断较晚、艾滋病期以及当前年龄超过50岁。相比之下，起始时免疫状态正常被检测为对DTG加3TC治疗成功具有刺激或促进作用。
