Department of Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Medical Microbiology, Translational Virology, University Medical Center Utrecht, Utrecht, The Netherlands.
J Med Virol. 2023 Oct;95(10):e29178. doi: 10.1002/jmv.29178.
The etiology of viral blips is not yet fully elucidated. One of the hypotheses is that blips reflect variations in residual viremia (RV) near the detectability threshold. In this study, we evaluated whether RV is associated with viral blips and which factors are associated with RV. All treatment regimens in 2010-2020 consisting of two nucleos(-t)ide reverse transcriptase inhibitors and one anchor (integrase strand transfer inhibitor [INSTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], or protease inhibitor [PI]) in people with HIV (PWH) were evaluated for RV (detectable viremia <50 cp/mL) and blips (isolated viral loads [VLs] 50-499 cp/mL between measurements <50 cp/mL). All medical records were reviewed and regimens in which a VL ≥ 50 cp/mL was deemed to result from non-adherence (based on the documented conclusion by the treating physician) were excluded. Factors associated with blips and RV were identified using generalized linear mixed models. In total, 24 518 VLs from 1658 PWH were analyzed. VLs were measured during INSTI- (n = 5119; 20.9%), PI- (n = 8935; 36.4%), and NNRTI-use (n = 10 464; 42.7%). VLs were categorized as blips in 1.4% (n = 332). The 24,186 non-blip VLs were RNA (no RV) (n = 15 326; 63.4%), 1-19 cp/mL (n = 6318; 26.1%), 20-49 cp/mL (n = 1620; 6.7%), or <50 cp/mL with an unknown RV level (n = 922; 3.8%). In 193/1658 PWH (11.6%), the RV level was RNA in all VLs assessed. RV 1-19 cp/mL and 20-49 cp/mL (vs. RNA ) were significantly associated with subsequent viral blips (respective odds ratio 2.66 and 4.90 [95% confidence intervals: 1.98-3.58 and 3.41-7.04]). Zenith VL and use of PIs (vs. INSTIs/NNRTIs) were associated with higher RV and blip odds. This large cohort study showed that blips were associated with higher preceding RV. Both the anchor type and factors previously linked to the latent viral reservoir were associated with RV, suggesting blips having a multifactorial origin.
病毒学突刺的病因尚未完全阐明。其中一种假设是，突刺反映了检测阈值附近残余病毒血症（RV）的变化。在这项研究中，我们评估了 RV 是否与病毒学突刺有关，以及哪些因素与 RV 有关。评估了 2010-2020 年所有包含两种核苷（酸）逆转录酶抑制剂和一种锚定物（整合酶链转移抑制剂[INSTI]、非核苷逆转录酶抑制剂[NNRTI]或蛋白酶抑制剂[PI]）的治疗方案中的 RV（可检测病毒载量[VL]＜50 cp/mL）和突刺（测量值之间的孤立 VL 50-499 cp/mL＜50 cp/mL）。所有病历均进行了回顾，排除了被认为是由于不依从性而导致 VL≥50 cp/mL 的方案（基于治疗医生的书面结论）。使用广义线性混合模型确定与突刺和 RV 相关的因素。总共分析了来自 1658 名 HIV 感染者的 24518 个 VL。在 INSTI （n=5119；20.9%）、PI （n=8935；36.4%）和 NNRTI （n=10464；42.7%）使用期间测量 VL。VL 被归类为突刺的比例为 1.4%（n=332）。24186 个非突刺 VL 为 RNA（无 RV）（n=15326；63.4%）、1-19 cp/mL（n=6318；26.1%）、20-49 cp/mL（n=1620；6.7%）或＜50 cp/mL 且 RV 水平未知（n=922；3.8%）。在 1658 名 PWH 中，193 名（11.6%）的所有评估 VL 中的 RV 水平均为 RNA。RV 1-19 cp/mL 和 20-49 cp/mL（与 RNA 相比）与随后的病毒学突刺显著相关（相应的比值比为 2.66 和 4.90[95%置信区间：1.98-3.58 和 3.41-7.04]）。Zenith VL 和 PI 的使用（与 INSTIs/NNRTIs 相比）与更高的 RV 和突刺几率相关。这项大型队列研究表明，突刺与先前更高的 RV 相关。锚定物类型和以前与潜伏病毒库相关的因素均与 RV 相关，表明突刺具有多因素起源。
