HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study
HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study
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DOI：
10.1093/cid/civ732
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发表时间：
2016-01-01
影响因子：
11.8
通讯作者：
Kouyos, Roger D.
中科院分区：
文献类型：
--
作者：
Marzel, Alex;Shilaih, Mohaned;Kouyos, Roger D.
背景在近期人类免疫缺陷病毒（HIV）感染期间减少传播的比例对于“治疗即预防”在人口水平上的成功至关重要。用19 604个Swiss序列和90 994个非Swiss背景序列构建了系统发育树。使用104种遗传距离（1%-2.5%）和自举（50%-100%）阈值的组合来确定瑞士传播对，以检查这些标准的效果。根据估计血清转换日期之间的时间间隔，将单系对分类为近期或慢性传播。通过调整临床和人口统计学特征的逻辑回归分析来确定与近期或慢性感染期间传播相关的危险因素。估计4079例患者的血清转换日期，包括71（距离，1%;自举，100%）至378传播对（距离，2.5%;自举，50%）。我们发现，43.7%（范围，41%-56%）的传播发生在感染的第一年。传播对的系统发育定义越高，最近阶段的传播分数越高。慢性期病毒载量曲线下面积（校正比值比，3; 95%置信区间，1.64-5.48）和抗逆转录病毒治疗（ART）开始时间（校正比值比1.4/y; 1.11-1.77）与慢性期传播相关，而不是近期传播。重要的是，至少有14%的慢性阶段传输事件发生后，发射机中断ART。我们表明，在最近的艾滋病毒感染，但也在瑞士中断抗逆转录病毒治疗后的慢性传播的高比例的传输。两者都是治疗和预防的关键问题，并强调了早期诊断和早期持续治疗的重要性。
Background. Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention".Methods. 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.Findings. 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.Conclusions. 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.