Preexposure prophylaxis (PrEP) is an effective HIV prevention tool, although effectiveness is dependent upon adherence. It is important to characterize the impact of PrEP on HIV antibody responses in people who experience breakthrough infections to understand the potential impact on timely diagnosis and treatment. Longitudinal HIV-1-specific antibody responses were evaluated in 42 people who inject drugs (PWID) from the Bangkok Tenofovir Study (BTS) (placebo = 28; PrEP = 14) who acquired HIV while receiving PrEP. HIV-1 antibody levels and avidity to three envelope proteins (gp41, gp160, and gp120) were measured in the plasma using a customized Bio-Plex (Bio-Rad Laboratories, Hercules, CA) assay. A time-to-event analysis was performed for each biomarker to compare the distribution of times at which study subjects exceeded the recent/long-term assay threshold, comparing PrEP and placebo treatment groups. We fit mixed-effects models to identify longitudinal differences in antibody levels and avidity between groups. Overall, longitudinal antibody levels and avidity were notably lower in the PrEP breakthrough group compared to the placebo group. Time-to-event analyses demonstrated a difference in time to antibody reactivity between treatment groups for all Bio-Plex biomarkers. Longitudinal gp120 antibody levels within the PrEP breakthrough group were decreased compared to the placebo group. When accounting for PrEP adherence, both gp120 and gp160 antibody levels were lower in the PrEP breakthrough group compared to the placebo group. We demonstrate hindered envelope antibody maturation in PWID who became infected while receiving PrEP in the BTS, which has significant implications for HIV diagnosis. Delayed maturation of the antibody response to HIV may increase the time to detection for antibody-based tests.

中文翻译：

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使用暴露前预防措施时 HIV-1 感染者的抗体反应改变

暴露前预防 (PrEP) 是一种有效的 HIV 预防工具，尽管有效性取决于依从性。重要的是要描述 PrEP 对经历突破性感染的人的 HIV 抗体反应的影响，以了解对及时诊断和治疗的潜在影响。在接受 PrEP 时感染 HIV 的曼谷替诺福韦研究 (BTS)（安慰剂 = 28；PrEP = 14）的 42 名注射吸毒者 (PWID) 中评估了纵向 HIV-1 特异性抗体反应。使用定制的 Bio-Plex (Bio-Rad Laboratories, Hercules, CA) 测定法测量血浆中的 HIV-1 抗体水平和对三种包膜蛋白（gp41、gp160 和 gp120）的亲和力。对每种生物标志物进行了事件发生时间分析，以比较研究对象超过近期/长期测定阈值的时间分布，比较 PrEP 和安慰剂治疗组。我们拟合混合效应模型来确定抗体水平和组间亲和力的纵向差异。总体而言，与安慰剂组相比，PrEP 突破组的纵向抗体水平和亲和力显着降低。事件发生时间分析表明，对于所有 Bio-Plex 生物标志物，治疗组之间的抗体反应时间存在差异。与安慰剂组相比，PrEP 突破组的纵向 gp120 抗体水平降低。考虑到 PrEP 依从性时，与安慰剂组相比，PrEP 突破组的 gp120 和 gp160 抗体水平均较低。我们在 BTS 中接受 PrEP 时被感染的 PWID 中的包膜抗体成熟受阻，这对 HIV 诊断具有重要意义。对 HIV 抗体反应的延迟成熟可能会增加基于抗体的检测的检测时间。