Bioinfoexperts, LLC, Thibodaux, Lousiana.
Bloomberg School of Public Health.
AIDS. 2020 Nov 15;34(14):2037-2044. doi: 10.1097/QAD.0000000000002662.
We investigated the duration of HIV transmission clusters.
Fifty-four individuals newly infected at enrollment in the ALIVE cohort were included, all of whom had sequences at an intake visit (T1) and from a second (T2) and/or a third (T3) follow-up visit, median 2.9 and 5.4 years later, respectively.
Sequences were generated using the 454 DNA sequencing platform for portions of HIV pol and env (HXB2 positions 2717-3230; 7941-8264). Genetic distances were calculated using tn93 and sequences were clustered over a range of thresholds (1--5%) using HIV-TRACE. Analyses were performed separately for individuals with pol sequences for T1 + T2 (n = 40, 'Set 1') and T1 + T3 (n = 25; 'Set 2'), and env sequences for T1 + T2 (n = 47, 'Set 1'), and T1 + T3 (n = 30; 'Set 2').
For pol, with one exception, a single cluster contained more than 75% of samples at all thresholds, and cluster composition was at least 90% concordant between time points/thresholds. For env, two major clusters (A and B) were observed at T1 and T2/T3, although cluster composition concordance between time points/thresholds was low (<60%) at lower thresholds for both sets 1 and 2. In addition, several individuals were included in clusters at T2/T3, although not at T1.
Caution should be used in applying a single threshold in population studies where seroconversion dates are unknown. However, the retention of some clusters even after 5 + years is evidence for the robustness of the clustering approach in general.
我们调查了 HIV 传播簇的持续时间。
在 ALIVE 队列中,共纳入了 54 名在入组时新感染的个体,他们都在入组时(T1)和第二次(T2)和/或第三次(T3)随访时进行了序列检测,中位时间分别为 2.9 年和 5.4 年后。
使用 454 DNA 测序平台对 HIV pol 和 env 的部分区域(HXB2 位置 2717-3230;7941-8264)进行了序列生成。使用 tn93 计算遗传距离,并使用 HIV-TRACE 在 1-5%的范围内对序列进行聚类。分别对 T1+T2(n=40,“Set 1”)和 T1+T3(n=25;“Set 2”)个体的 pol 序列,以及 T1+T2(n=47,“Set 1”)和 T1+T3(n=30;“Set 2”)个体的 env 序列进行了分析。
对于 pol,除一个例外,在所有阈值下,一个单一的簇包含了超过 75%的样本,并且簇组成在时间点/阈值之间至少有 90%的一致性。对于 env,在 T1 和 T2/T3 时观察到两个主要的簇(A 和 B),尽管在两个集 1 和 2 的较低阈值下,时间点/阈值之间的簇组成一致性较低(<60%)。此外,一些个体在 T2/T3 时被包含在簇中,尽管在 T1 时没有。
在不知道血清转换日期的人群研究中,应用单一阈值时应谨慎。然而,即使在 5 年以上的时间里,一些簇仍然保留,这证明了聚类方法的一般稳健性。