HIV-1 reservoir landscape of post-treatment control.

Current opinion in HIV and AIDS Pub Date : 2025-01-01 Epub Date: 2024-10-21 DOI:10.1097/COH.0000000000000891
Caroline Charre, Yanis Merad, Véronique Avettand-Fenoel
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Abstract

Purpose of review: This review explores the viral reservoir landscape in individuals who control viral replication after treatment interruption (TI), designated as post-treatment controllers (PTCs). Identifying their virologic features is crucial to inform drug-free HIV remission strategies.

Recent findings: Traditionally characterized as small, likely due to early treatment, the viral reservoir of PTCs, after TI, exhibits limited transcriptional activity, residual viral replication and subsequent proviral diversity. Intact proviruses are found to be restricted. In nonhuman primate PTCs, this depletion of intact proviruses is already observed in lymph nodes before TI, suggesting that control mechanisms begin during antiretroviral therapy. Furthermore, recent studies suggest immune-driven proviral deep latency associated with repressive epigenetic features and integration sites in PTCs. While molecular mapping of virological features of PTCs is increasingly precise and coupled with in-depth immunologic assays, robust predictive biomarkers of PTCs are still lacking.

Summary: Despite limited sample sizes and heterogeneous definitions, common virologic features of PTCs include restricted reservoir size and transcriptional activity, fewer intact proviruses and deep proviral latency. Ongoing research using innovative technologies will further elucidate the mechanisms underlying post-treatment control, paving the way for successful HIV cure interventions.

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治疗后控制的 HIV-1 病毒库状况。
综述目的:本综述探讨了治疗中断(TI)后控制病毒复制的个体(即治疗后控制者(PTC))的病毒库情况。确定他们的病毒学特征对于制定无药 HIV 缓解策略至关重要:传统上,PTCs 的病毒库很小,这可能是由于早期治疗的缘故,但治疗后控制者的病毒库表现出有限的转录活性、残余病毒复制和随后的前病毒多样性。完整的前病毒受到限制。在非人灵长类 PTCs 中,TI 之前就已在淋巴结中观察到这种完整前病毒的消耗,这表明控制机制始于抗逆转录病毒治疗期间。此外,最近的研究表明,免疫驱动的前病毒深度潜伏与 PTC 的抑制性表观遗传特征和整合位点有关。尽管 PTC 病毒学特征的分子图谱越来越精确,并与深入的免疫学检测相结合,但仍缺乏强有力的 PTC 预测生物标志物。摘要:尽管样本量有限且定义不一,但 PTC 的共同病毒学特征包括储库规模和转录活性受限、完整的前病毒较少以及前病毒深度潜伏。利用创新技术进行的持续研究将进一步阐明治疗后控制的基本机制,为成功治愈艾滋病干预措施铺平道路。
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