Department of Medicine, University of North Carolina at Chapel Hill (UNC) School of Medicine.
UNC Chapel Hill HIV Cure Center.
AIDS. 2020 Nov 1;34(13):1923-1931. doi: 10.1097/QAD.0000000000002652.
The aim of this study was to evaluate penetration of antiretrovirals into compartments and efficacy of a dual, NRTI-sparing regimen in acute HIV infection (AHI).
Single-arm, open-label pilot study of participants with AHI initiating ritonavir-boosted darunavir 800 mg once daily and etravirine 400 mg once daily or 200 mg twice daily within 30 days of AHI diagnosis.
Efficacy was defined as HIV RNA less than 200 copies/ml by week 24. Optional sub-studies included pharmacokinetics analysis from genital fluids (weeks 0-4, 12, 48), cerebrospinal fluid (CSF) (weeks 2-4, 24 and 48) and endoscopic biopsies (weeks 4-12 and 36-48). Neuropsychological performance was assessed at weeks 0, 24 and 48.
Fifteen AHI participants were enrolled. Twelve (80%) participants achieved HIV RNA less than 200 copies/ml by week 24. Among 12 participants retained through week 48, nine (75%) remained suppressed to less than 50 copies/ml. The median time from ART initiation to suppression less than 200 and less than 50 copies/ml was 59 and 86 days, respectively. The penetration ratios for etravirine and darunavir in gut associated lymphoid tissue were 19.2 and 3.05, respectively. Most AHI participants achieving viral suppression experienced neurocognitive improvement. Of the three participants without overall improvement in neurocognitive functioning as measured by impairment ratings (more than two tests below 1 SD), two had virologic failure.
NRTI-sparing ART started during AHI resulted in rapid viral suppression similar to NRTI-based regimens. More novel and compact two-drug treatments for AHI should be considered. Early institution of ART during AHI appears to improve overall neurocognitive function and may reduce the risk of subsequent neurocognitive impairment. CLINICALTRIALS.GOV:: NCT00855413.
本研究旨在评估抗逆转录病毒药物进入各部位的情况，并评估急性 HIV 感染（AHI）中使用双重、不使用 NRTI 的方案的疗效。
AHI 诊断后 30 天内，参与者每日接受一次利托那韦增强的达芦那韦 800mg 和依曲韦林 400mg 或 200mg 每日两次治疗，进行单臂、开放标签的初步研究。
疗效定义为第 24 周时 HIV RNA 小于 200 拷贝/ml。可选的子研究包括从生殖器液（第 0-4、12、48 周）、脑脊液（CSF）（第 2-4、24 和 48 周）和内镜活检（第 4-12 周和 36-48 周）进行药代动力学分析。在第 0、24 和 48 周时评估神经心理学表现。
共纳入 15 名 AHI 参与者。12 名（80%）参与者在第 24 周时 HIV RNA 小于 200 拷贝/ml。在 12 名随访至第 48 周的参与者中，9 名（75%）持续抑制至小于 50 拷贝/ml。从开始 ART 到抑制到小于 200 拷贝/ml 和小于 50 拷贝/ml 的中位数时间分别为 59 和 86 天。依曲韦林和达芦那韦在肠道相关淋巴组织中的穿透率分别为 19.2 和 3.05。大多数实现病毒抑制的 AHI 参与者的神经认知功能得到改善。在通过损害评分（超过两项测试低于 1 SD）测量的神经认知功能整体改善的三名参与者中，有两名发生了病毒学失败。
在 AHI 期间开始使用不使用 NRTI 的 ART 可快速抑制病毒，与基于 NRTI 的方案相似。对于 AHI，应考虑更新型和更紧凑的两药治疗。在 AHI 期间早期开始 ART 似乎可以改善整体神经认知功能，并可能降低随后发生神经认知障碍的风险。CLINICALTRIALS.GOV:: NCT00855413。
