Franceschi Vinicius B, Drake Kieran O, Bibby David F, Sabin Caroline A, Dunn David T, Mbisa Jean L, Volz Erik M
MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, 90 Wood Lane, London W12 0BZ, United Kingdom.
Antiviral Unit, Virus Reference Department, UK Health Security Agency, 61 Colindale Avenue, London NW9 5EQ, United Kingdom.
Virus Evol. 2025 May 20;11(1):veaf048. doi: 10.1093/ve/veaf048. eCollection 2025.
The evolution of HIV-1 virulence has significant implications for epidemic control. Recent phylogenomic analyses identified low-prevalence HIV-1 variants exhibiting significant differences in disease progression. We analysed 40 888 partial HIV-1 pol sequences from the UK HIV Drug Resistance Database (UKRDB) across subtypes B, C, A1, and CRF02AG. We identified phylotypes with putative differences in transmission/phylogenetic patterns and assessed their virulence trends using pretreatment viral loads, CD4 cell counts, and four statistical methods. We classified three subtype B phylotypes-PT.B.40.UK, PT.B.69.UK, and PT.B.133.UK -as variants of interest (VOIs) due to significantly higher viral loads and/or accelerated CD4 decline. PT.B.40.UK and PT.B.69.UK exhibited higher viral loads, 4.93 log copies/ml (95% CI: 4.73-5.13) and 4.87 (4.65-5.10), representing 0.30-0.36 log copies/ml higher than the reference group (4.57; 4.55-4.59). Despite uncertainties in baseline CD4 counts, all three VOIs reached the clinically relevant threshold of 350 CD4 cells/mm significantly faster than the reference group (3.5 years, 3.1-3.9 years): 2.3 years (1.0-5.1) for PT.B.40.UK, 2.0 years (10.8 months-4.4 years) for PT.B.69.UK, and 1.8 years (10.8 months-3.6 years) for PT.B.133.UK. These VOIs and their closest relatives have been circulating in the UK for decades with limited international spread and did not exhibit unusually rapid growth rates. Although these findings suggest a heritable high-virulence HIV-1 phenotype, we did not find evidence that convergent genetic polymorphisms or switches in coreceptor usage explained these differences. The small fraction of HIV-1 subtype B variants in the UK evolving towards higher virulence is unlikely to pose a public health concern, given the ongoing decline in new HIV diagnoses following the widespread adoption of pre-exposure prophylaxis and targeted prevention campaigns. However, this study-alongside the detection of the VB variant in the Netherlands-demonstrates that more virulent variants are not rare and can emerge independently in multiple countries. Consequently, HIV-1 genomic surveillance remains crucial to monitor HIV-1 virulence and mitigate its healthcare impact.
HIV-1毒力的演变对疫情控制具有重大影响。最近的系统发育基因组分析发现，低流行率的HIV-1变体在疾病进展方面存在显著差异。我们分析了来自英国HIV耐药数据库（UKRDB）的40888条HIV-1 pol部分序列，涵盖B、C、A1和CRF02AG亚型。我们识别出在传播/系统发育模式上可能存在差异的系统型，并使用治疗前病毒载量、CD4细胞计数和四种统计方法评估它们的毒力趋势。我们将三种B亚型系统型——PT.B.40.UK、PT.B.69.UK和PT.B.133.UK——归类为感兴趣的变体（VOIs），因为它们的病毒载量显著更高和/或CD4下降加速。PT.B.40.UK和PT.B.69.UK的病毒载量更高，分别为4.93 log拷贝/毫升（95%置信区间：4.73 - 5.13）和4.87（4.65 - 5.10），比参考组（4.57；4.55 - 4.59）高0.30 - 0.36 log拷贝/毫升。尽管基线CD4计数存在不确定性，但所有三种VOIs达到临床相关阈值350个CD4细胞/立方毫米的速度明显快于参考组（3.5年，3.1 - 3.9年）：PT.B.40.UK为2.3年（1.0 - 5.1年），PT.B.69.UK为2.0年（10.8个月 - 4.4年），PT.B.133.UK为1.8年（10.8个月 - 3.6年）。这些VOIs及其最密切的亲属在英国已经传播了数十年，国际传播有限，且未表现出异常快速的增长率。尽管这些发现表明存在可遗传的高毒力HIV-1表型，但我们没有发现证据表明趋同的基因多态性或共受体使用的转变可以解释这些差异。鉴于暴露前预防的广泛采用和针对性预防活动后新HIV诊断病例持续下降，英国向更高毒力演变的HIV-1 B亚型变体比例较小不太可能构成公共卫生问题。然而，这项研究——以及在荷兰检测到VB变体——表明更具毒力的变体并不罕见，并且可以在多个国家独立出现。因此，HIV-1基因组监测对于监测HIV-1毒力并减轻其对医疗保健的影响仍然至关重要。
