Li Yifan, Dearlove Bethany L, Lewitus Eric, Bai Hongjun, Shangguan Shida, Pham Phuc, Bose Meera, Sanders-Buell Eric, Miller Shana Howell, Rosario Yvonne, Ehrenberg Philip K, Tovanabutra Sodsai, Thomas Rasmi, Ake Julie A, Vasan Sandhya, Eller Leigh Anne, Nitayaphan Sorachai, Maganga Lucas, Kibuuka Hannah, Sawe Fredrick K, Robb Merlin L, Rolland Morgane
U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
J Int AIDS Soc. 2025 Aug;28(8):e70016. doi: 10.1002/jia2.70016.
Cases of spontaneous control of HIV-1 can help define strategies to induce remission. Since the identification of viral control in the absence of treatment typically occurs after a prolonged period post-HIV-1 diagnosis, our knowledge of the early events after HIV-1 acquisition that led to viral control is limited.
The RV217 prospective cohort enrolled 2276 participants in East Africa (Kenya, Uganda, Tanzania) and Thailand between 2009 and 2015. We analysed HIV-1 sequences and clinical data from 102 individuals who were diagnosed with acute HIV-1 infection and had a negative HIV-1 RNA test in the week before. We focused on 69 participants with longitudinal follow-up and identified viraemic controllers who maintained viral loads <2000 copies/ml for over a year without treatment. We evaluated viral genetic and clinical features that are associated with viral control.
Eleven women from East Africa showed control of viral replication for an average duration of 891 (range: 405-1425) days within an average of 130 days from diagnosis. The majority were living with subtype A1 (n = 6), or A1 recombinant strains (n = 4), with one living with subtype D; 10 were from Kenya, one from Uganda. Controllers had significantly slower CD4+ T cell decline (p = 0.028) and higher Natural Killer (NK) cell counts (p = 0.047) than non-controllers, but none carried human leukocyte antigen (HLA) alleles previously reported to be associated with viral control. Peak viraemia was recorded at an average of 541 million copies/ml with no difference between controllers and non-controllers (p = 0.97). Viral loads became lower in controllers (3459 copies/ml) than in non-controllers (23,157 copies/ml) as early as nadir viraemia (p = 0.009), with a more significant difference observed at set point (1069 vs. 24,084 copies/ml, respectively; p<0.0001).
Our findings confirm the role of HIV-1 subtype A1 in mediating viral control. The fact that controllers showed high viral loads in acute infection indicates that these viruses were not intrinsically impaired for replication, underlining the intersection between host immunity and favourable genotypes in the subsequent control of HIV-1. These data suggest that conducting HIV-1 remission studies in East Africa could provide favourable conditions to achieve durable post-treatment control of viraemia.
HIV-1自发控制的病例有助于确定诱导缓解的策略。由于在未接受治疗的情况下病毒控制的识别通常发生在HIV-1诊断后的较长时间，我们对HIV-1感染后导致病毒控制的早期事件的了解有限。
RV217前瞻性队列在2009年至2015年间招募了东非（肯尼亚、乌干达、坦桑尼亚）和泰国的2276名参与者。我们分析了102名被诊断为急性HIV-1感染且在之前一周HIV-1 RNA检测呈阴性的个体的HIV-1序列和临床数据。我们重点关注了69名有纵向随访的参与者，并确定了在未接受治疗的情况下病毒载量维持<2000拷贝/毫升超过一年的病毒血症控制者。我们评估了与病毒控制相关的病毒基因和临床特征。
来自东非的11名女性在诊断后平均130天内显示出病毒复制控制，平均持续时间为891天（范围：405 - 1425天）。大多数感染的是A1亚型（n = 6）或A1重组毒株（n = 4），1名感染的是D亚型；10名来自肯尼亚，1名来自乌干达。与非控制者相比，控制者的CD4 + T细胞下降明显更慢（p = 0.028），自然杀伤（NK）细胞计数更高（p = 0.047），但均未携带先前报道与病毒控制相关的人类白细胞抗原（HLA）等位基因。峰值病毒血症平均记录为5.41亿拷贝/毫升，控制者和非控制者之间无差异（p = 0.97）。早在病毒血症最低点时，控制者的病毒载量（3459拷贝/毫升）就低于非控制者（23157拷贝/毫升）（p = 0.009），在设定点时差异更显著（分别为1069和24084拷贝/毫升；p<0.0001）。
我们的研究结果证实了HIV-1 A1亚型在介导病毒控制中的作用。控制者在急性感染中显示出高病毒载量这一事实表明这些病毒在复制方面并非本质上受损，这突出了宿主免疫与后续HIV-1控制中有利基因型之间的交叉作用。这些数据表明在东非开展HIV-1缓解研究可为实现持久的治疗后病毒血症控制提供有利条件。
