PDF(Pubmed)
Abstract：
The persistence of the latent viral reservoir is the main hurdle to curing HIV-1 infection. SIV infection of non-human primates (NHPs), namely Indian-origin rhesus macaques, is the most relevant and widely used animal model to evaluate therapies that seek to eradicate HIV-1. The utility of a model ultimately rests on how accurately it can recapitulate human disease, and while reservoirs in the NHP model behave quantitatively very similar to those of long-term suppressed persons with HIV-1 (PWH) in the most salient aspects, recent studies have uncovered key nuances at the clonotypic level that differentiate the two in qualitative terms. In this review, we will highlight differences relating to proviral intactness, clonotypic structure, and decay rate during ART between HIV-1 and SIV reservoirs and discuss the relevance of these distinctions in the interpretation of HIV-1 cure strategies. While these, to some degree, may reflect a unique biology of the virus or host, distinctions among the proviral landscape in SIV are likely to be shaped significantly by the condensed timeframe of NHP studies. ART is generally initiated earlier in the disease course, and animals are virologically suppressed for shorter periods before receiving interventions. Because these are experimental variables dictated by the investigator, we offer guidance on study design for cure-related studies performed in the NHP model. Finally, we highlight the case of GS-9620 (Vesatolimod), an antiviral TLR7 agonist tested in multiple independent pre-clinical studies in which virological outcomes may have been influenced by study-related variables.
摘要：
潜伏病毒库的持续存在是治愈HIV-1感染的主要障碍。非人灵长类动物（NHP）的SIV感染，即印度裔恒河猴，是最相关和广泛使用的动物模型来评估寻求根除HIV-1的疗法。模型的实用性最终取决于它能准确地概括人类疾病，尽管NHP模型中的水库在最突出的方面与长期受抑制的HIV-1（PWH）患者的数量非常相似，最近的研究发现了在克隆型水平上的关键细微差别，在定性方面区分了这两者。在这次审查中,我们将强调与自然完整性有关的差异，克隆型结构，以及ART期间HIV-1和SIV储库之间的衰减率，并讨论这些区别在解释HIV-1治愈策略中的相关性。而这些,在某种程度上,可能反映了病毒或宿主的独特生物学特性，NHP研究的浓缩时间框架可能会对SIV中的前动物景观之间的区别产生重大影响。ART通常在疾病过程的早期开始，在接受干预之前，动物在病毒学上受到抑制的时间较短。因为这些是由研究者决定的实验变量，我们为在NHP模型中进行的治愈相关研究的研究设计提供指导.最后,我们重点介绍了GS-9620（Vesatolimod）的情况，在多项独立的临床前研究中测试了抗病毒TLR7激动剂,其中病毒学结局可能受到研究相关变量的影响.
