Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Viruses. 2023 Oct 6;15(10):2055. doi: 10.3390/v15102055.
A cure for HIV-1 (HIV) remains unrealized due to a reservoir of latently infected cells that persist during antiretroviral therapy (ART), with reservoir size associated with adverse health outcomes and inversely with time to viral rebound upon ART cessation. Once established during ART, the HIV reservoir decays minimally over time; thus, understanding factors that impact the size of the HIV reservoir near its establishment is key to improving the health of people living with HIV and for the development of novel cure strategies. Yet, to date, few correlates of HIV reservoir size have been identified, particularly in pediatric populations. Here, we employed a cross-subtype intact proviral DNA assay (CS-IPDA) to quantify HIV provirus between one- and two-years post-ART initiation in a cohort of Kenyan children (n = 72), which had a median of 99 intact (range: 0-2469), 1340 defective (range: 172-3.84 × 10), and 1729 total (range: 178-5.11 × 10) HIV proviral copies per one million T cells. Additionally, pre-ART plasma was tested for HIV Env-specific antibody-dependent cellular cytotoxicity (ADCC) activity. We found that pre-ART gp120-specific ADCC activity inversely correlated with defective provirus levels (n = 68, r = -0.285, = 0.0214) but not the intact reservoir (n = 68, r = -0.0321, -value = 0.800). Pre-ART gp41-specific ADCC did not significantly correlate with either proviral population (n = 68; intact: r = -0.0512, -value = 0.686; defective: r = -0.109, -value = 0.389). This suggests specific host immune factors prior to ART initiation can impact proviruses that persist during ART.
由于在抗逆转录病毒治疗（ART）期间持续存在潜伏感染的细胞库，HIV-1（HIV）仍然无法治愈，而储库的大小与不良健康结果相关，与 ART 停止后病毒反弹的时间成反比。在 ART 期间建立后，HIV 储库随时间的推移最小化衰减；因此，了解影响 HIV 储库在建立时大小的因素是改善 HIV 感染者健康和开发新的治愈策略的关键。然而，迄今为止，很少有 HIV 储库大小的相关因素被确定，特别是在儿科人群中。在这里，我们使用跨亚型完整前病毒 DNA 测定法（CS-IPDA）在肯尼亚儿童队列中（n = 72），在 ART 启动后一到两年内定量 HIV 前病毒，中位数为 99 个完整（范围：0-2469），1340 个缺陷（范围：172-3.84×10）和 1729 个总（范围：178-5.11×10）HIV 前病毒拷贝数/百万 T 细胞。此外，还检测了 ART 前血浆中的 HIV Env 特异性抗体依赖性细胞毒性（ADCC）活性。我们发现，ART 前 gp120 特异性 ADCC 活性与缺陷前病毒水平呈负相关（n = 68，r = -0.285，p = 0.0214），但与完整储库无关（n = 68，r = -0.0321，p 值 = 0.800）。ART 前 gp41 特异性 ADCC 与两个前病毒群体均无显著相关性（n = 68；完整：r = -0.0512，p 值 = 0.686；缺陷：r = -0.109，p 值 = 0.389）。这表明在开始 ART 之前，特定的宿主免疫因素可能会影响在 ART 期间持续存在的前病毒。
