BACKGROUND Antiretroviral therapy (ART) has improved the clinical management of HIV-1 infection. However, little is known about how the latest ART recommendations affect the heterogeneity of HIV-1 reservoir size. METHODS We used a complete statistical approach to outline parameters underlying diversity in HIV-1 reservoir size in a cohort of 892 people with HIV-1 (PWH) on suppressive ART for >3 years. Total HIV-1-DNA levels were measured in PBMCs using digital droplet PCR (ddPCR). RESULTS We classified 179 (20%) participants as Low Viral Reservoir Treated (LoViReT, <50 HIV-1-DNA copies/106 PBMCs). Twenty variables were collected to explore their association with the LoViReT phenotype using machine learning approaches. Nadir CD4 and zenith pre-ART viral load were closely associated with LoViReT status, with lower CD4 recovery, shorter time from diagnosis to undetectable viral load, and initiation of treatment with an integrase inhibitor (InSTI)-containing regimen. Initiating ART with any InSTI was also associated with shorter time to undetectable viremia. Locally estimated scatterplot smoothing (LOESS) regression revealed a progressive reduction in the size of the HIV-1 reservoir in individuals who started ART after 2007. Similarly, higher nadir CD4 and shorter time to undetectable viremia were observed when treatment was initiated after that year. CONCLUSION Our findings demonstrate that the progressive implementation of earlier, universal treatment at diagnosis and the use of InSTIs affect the size of the HIV-1 reservoir. Our work shows that effective management of infection is the first step toward reducing the reservoir and brings us closer to achieving a cure. FUNDING U.S. National Institutes of Health, Division of AIDS at the National Institute of Allergy and Infectious Diseases, Merck Sharp & Dohme.

中文翻译：

---

评估 HIV-1 宿主临床抗逆转录病毒治疗三十年的进展。


背景 抗逆转录病毒疗法 （ART） 改善了 HIV-1 感染的临床管理。然而，关于最新的 ART 建议如何影响 HIV-1 储层大小的异质性，人们知之甚少。方法 我们使用完整的统计方法来概述在 892 名接受抑制性 ART 的 HIV-1 患者 （PWH） 队列中 HIV-1 储库大小差异的参数 >3 年。使用数字液滴 PCR （ddPCR） 测量 PBMC 中的总 HIV-1-DNA 水平。结果我们将 179 名 （20%） 参与者归类为低病毒库治疗 （LoViReT，<50 HIV-1-DNA 拷贝/106 个 PBMC）。使用机器学习方法收集了 20 个变量以探索它们与 LoViReT 表型的关联。最低点 CD4 和天顶 ART 前病毒载量与 LoViReT 状态密切相关，CD4 恢复较低，从诊断到病毒载量检测不到的时间较短，并且开始使用含整合酶抑制剂 （InSTI） 的方案进行治疗。使用任何 InSTI 开始 ART 也与较短的病毒血症检测不到的时间有关。局部估计散点图平滑 （LOESS） 回归显示，在 2007 年之后开始 ART 的个体中，HIV-1 储库的大小逐渐减小。同样，在该年之后开始治疗时，观察到较高的最低点 CD4 和较短的检测不到病毒血症的时间。结论 我们的研究结果表明，在诊断时逐步实施早期、普遍的治疗和 InSTIs 的使用会影响 HIV-1 宿主的大小。我们的研究表明，有效管理感染是减少宿主的第一步，使我们更接近治愈。资助美国 国立卫生研究院，国家过敏和传染病研究所的艾滋病部门，默克夏普和Dohme。