与基于蛋白酶抑制剂的治疗相比，基于非核苷类逆转录酶抑制剂的联合抗逆转录病毒疗法与较低的细胞相关 HIV RNA 和 DNA 水平相关。
Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels compared to protease inhibitor-based therapy.
机构信息
Amsterdam UMC, University of Amsterdam, Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.
Amsterdam UMC, University of Amsterdam, Laboratory of Viral Immune Pathogenesis, Department of Experimental Immunology, Amsterdam, Netherlands.
出版信息
Elife. 2021 Aug 13;10:e68174. doi: 10.7554/eLife.68174.
BACKGROUND
It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).
METHODS
CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4 count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART.
RESULTS
In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (p = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (p = 0.048 and p = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals.
CONCLUSIONS
All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size.
FUNDING
This work was supported by ZonMw (09120011910035) and FP7 Health (305522).
背景
目前尚不清楚联合抗逆转录病毒疗法（ART）方案在完全抑制人类免疫缺陷病毒（HIV）复制方面的能力是否存在差异。在这里，我们报告了两项横断面研究的结果，这些研究比较了接受包含非核苷类逆转录酶抑制剂（NNRTI）或蛋白酶抑制剂（PI）的抑制性 ART 方案的个体之间细胞相关（CA）HIV 标志物的水平。
方法
在由两种核苷逆转录酶抑制剂（NRTIs）加 NNRTI 或 PI 组成的三联 ART 方案中，对两个队列（n=100，n=124）的个体进行了 CA HIV 未剪接 RNA 和总 HIV DNA 的定量。为了比较方案之间的 CA HIV RNA 和 DNA 水平，我们构建了多变量模型，调整了年龄、性别、当前和最低点 CD4 计数、血浆病毒载量峰值、病毒学抑制持续时间、NRTI 骨架组成、低水平血浆 HIV RNA 可检测性以及电子测量的 ART 依从性。
结果
在两个队列中，CA HIV RNA 和 DNA 水平均呈强相关性（rho=0.70 和 rho=0.54），且 NNRTI 治疗组的两种标志物均低于 PI 治疗组。在多变量分析中，两个队列中的 CA RNA 在 NNRTI 治疗组中均显著降低（两个队列中的 p=0.02），而 ART 方案与总 HIV DNA 之间的相关性相似但较弱（p=0.048 和 p=0.10）。在单个 NNRTI 或单个 PI 之间，CA HIV RNA 或 DNA 水平没有差异，但与 PI 治疗组相比，接受奈韦拉平或依法韦仑治疗的个体的 CA HIV RNA 水平较低。
结论
所有当前类别的抗逆转录病毒药物仅能预防新细胞的感染，但不能抑制长寿储库细胞中的 HIV RNA 转录。因此，治疗方案对 CA HIV RNA 和 DNA 水平的这些差异表明，NNRTI 比 PI 更能抑制 HIV 残留复制，这可能导致病毒储存库的体积更小。
资助
这项工作得到了 ZonMw（09120011910035）和 FP7 健康（305522）的支持。
Zotero 插件