Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich.
Institute of Medical Virology, University of Zurich.
Clin Infect Dis. 2016 Jan 1;62(1):115-122. doi: 10.1093/cid/civ732. Epub 2015 Sep 19.
Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention".
A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection.
Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART.
We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.
降低近期人类免疫缺陷病毒 (HIV) 感染期间的传播比例对于“治疗即预防”在人群层面的成功至关重要。
利用 19604 例瑞士序列和 90994 例非瑞士背景序列构建了系统进化树。使用 104 种遗传距离 (1%-2.5%) 和 bootstrap (50%-100%) 阈值组合来识别瑞士传播对,以检验这些标准的效果。基于估计的血清转换日期之间的时间间隔,将单系传播对分类为近期或慢性传播。使用调整临床和人口统计学特征的逻辑回归来识别与近期或慢性感染期间传播相关的危险因素。
在系统进化树上估计了 4079 例患者的血清转换日期,包括 71 个 (距离,1%;bootstrap,100%) 至 378 个传播对 (距离,2.5%;bootstrap,50%)。我们发现,43.7% (范围,41%-56%) 的传播发生在感染的第一年。更严格的传播对系统进化定义与近期相传播比例更高相关。慢性相病毒载量曲线下面积 (调整比值比,3;95%置信区间,1.64-5.48) 和开始抗逆转录病毒治疗 (ART) 的时间 (调整比值比 1.4/y;1.11-1.77) 与慢性相传播而非近期传播相关。重要的是,在瑞士,至少有 14%的慢性相传播事件发生在传播者中断 ART 之后。
我们证明了瑞士近期 HIV 感染期间存在高比例的传播,但也存在 ART 中断后的慢性传播。这两者都是“治疗即预防”的关键问题,并强调了早期诊断以及早期和持续治疗的重要性。