Department of Medicine, Georgetown University, Washington, DC 20057, USA.
HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA.
Viruses. 2022 Dec 25;15(1):68. doi: 10.3390/v15010068.
Background: Molecular epidemiological approaches provide opportunities to characterize HIV transmission dynamics. We analyzed HIV sequences and virus load (VL) results obtained during routine clinical care, and individual’s zip-code location to determine utility of this approach. Methods: HIV-1 pol sequences aligned using ClustalW were subtyped using REGA. A maximum likelihood (ML) tree was generated using IQTree. Transmission clusters with ≤3% genetic distance (GD) and ≥90% bootstrap support were identified using ClusterPicker. We conducted Bayesian analysis using BEAST to confirm transmission clusters. The proportion of nucleotides with ambiguity ≤0.5% was considered indicative of early infection. Descriptive statistics were applied to characterize clusters and group comparisons were performed using chi-square or t-test. Results: Among 2775 adults with data from 2014−2015, 2589 (93%) had subtype B HIV-1, mean age was 44 years (SD 12.7), 66.4% were male, and 25% had nucleotide ambiguity ≤0.5. There were 456 individuals in 193 clusters: 149 dyads, 32 triads, and 12 groups with ≥ four individuals per cluster. More commonly in clusters were males than females, 349 (76.5%) vs. 107 (23.5%), p < 0.0001; younger individuals, 35.3 years (SD 12.1) vs. 44.7 (SD 12.3), p < 0.0001; and those with early HIV-1 infection by nucleotide ambiguity, 202/456 (44.3%) vs. 442/2133 (20.7%), p < 0.0001. Members of 43/193 (22.3%) of clusters included individuals in different jurisdictions. Clusters ≥ four individuals were similarly found using BEAST. HIV-1 viral load (VL) ≥3.0 log10 c/mL was most common among individuals in clusters ≥ four, 18/21, (85.7%) compared to 137/208 (65.8%) in clusters sized 2−3, and 927/1169 (79.3%) who were not in a cluster (p < 0.0001). Discussion: HIV sequence data obtained for HIV clinical management provide insights into regional transmission dynamics. Our findings demonstrate the additional utility of HIV-1 VL data in combination with phylogenetic inferences as an enhanced contact tracing tool to direct HIV treatment and prevention services. Trans-jurisdictional approaches are needed to optimize efforts to end the HIV epidemic.
分子流行病学方法为描述 HIV 传播动力学提供了机会。我们分析了在常规临床护理中获得的 HIV 序列和病毒载量 (VL) 结果,以及个体的邮政编码位置,以确定该方法的效用。
使用 ClustalW 对齐 HIV-1 pol 序列,使用 REGA 进行亚型分析。使用 IQTree 生成最大似然 (ML) 树。使用 ClusterPicker 识别遗传距离 (GD) ≤3%且支持度≥90%的传播簇。我们使用 BEAST 进行贝叶斯分析以确认传播簇。核苷酸歧义率≤0.5%的比例被认为是早期感染的指标。使用描述性统计来描述簇,使用卡方检验或 t 检验进行组间比较。
在 2014-2015 年期间有数据的 2775 名成年人中,2589 人 (93%) 感染了 B 型 HIV-1,平均年龄为 44 岁 (SD 12.7),66.4%为男性,25%的核苷酸歧义率≤0.5。有 456 人分布在 193 个簇中:149 对,32 个三联体,12 个每组有≥4 人。簇中更常见的是男性而不是女性,349 人 (76.5%) 与 107 人 (23.5%) 相比,p<0.0001;更年轻的个体,35.3 岁 (SD 12.1) 与 44.7 岁 (SD 12.3) 相比,p<0.0001;以及核苷酸歧义率指示的早期 HIV-1 感染者,202/456 (44.3%) 与 442/2133 (20.7%) 相比,p<0.0001。43/193 (22.3%)的簇成员包括不同司法管辖区的个体。使用 BEAST 也发现了≥4 人的簇。在≥4 人的簇中,HIV-1 病毒载量 (VL)≥3.0 log10 c/mL 最为常见,21 人中 18 人 (85.7%) 与 2-3 人的簇中 137 人 (65.8%) 相比,以及与不在簇中的 927 人 (79.3%) 相比,p<0.0001。
在 HIV 临床管理中获得的 HIV 序列数据为了解区域传播动力学提供了新的见解。我们的研究结果表明,HIV-1 VL 数据与系统发育推断相结合,作为一种增强的接触者追踪工具,在指导 HIV 治疗和预防服务方面具有额外的效用。需要采取跨司法管辖区的方法,以优化努力,结束艾滋病毒流行。