Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
PLoS One. 2018 Jul 5;13(7):e0198999. doi: 10.1371/journal.pone.0198999. eCollection 2018.
South Africa has one of the highest rates of HIV-1 (HIV) infection world-wide, with the highest rates among young women. We analyzed the molecular epidemiology and evolutionary history of HIV in young women attending high school in rural South Africa.
Samples were obtained from the HPTN 068 randomized controlled trial, which evaluated the effect of cash transfers for school attendance on HIV incidence in women aged 13-20 years (Mpumalanga province, 2011-2015). Plasma samples from HIV-infected participants were analyzed using the ViroSeq HIV-1 Genotyping assay. Phylogenetic analysis was performed using 200 pol gene study sequences and 2,294 subtype C reference sequences from South Africa. Transmission clusters were identified using Cluster Picker and HIV-TRACE, and were characterized using demographic and other epidemiological data. Phylodynamic analyses were performed using the BEAST software.
The study enrolled 2,533 young women who were followed through their expected high school graduation date (main study); some participants had a post-study assessment (follow-up study). Two-hundred-twelve of 2,533 enrolled young women had HIV infection. HIV pol sequences were obtained for 94% (n = 201/212) of the HIV-infected participants. All but one of the sequences were HIV-1 subtype C; the non-C subtype sequence was excluded from further analysis. Median pairwise genetic distance between the subtype C sequences was 6.4% (IQR: 5.6-7.2). Overall, 26% of study sequences fell into 21 phylogenetic clusters with 2-6 women per cluster. Thirteen (62%) clusters included women who were HIV-infected at enrollment. Clustering was not associated with study arm, demographic or other epidemiological factors. The estimated date of origin of HIV subtype C in the study population was 1958 (95% highest posterior density [HPD]: 1931-1980), and the median estimated substitution rate among study pol sequences was 1.98x10-3 (95% HPD: 1.15x10-3-2.81x10-3) per site per year.
Phylogenetic analysis suggests that multiple HIV subtype C sublineages circulate among school age girls in South Africa. There were no substantive differences in the molecular epidemiology of HIV between control and intervention arms in the HPTN 068 trial.
南非是全球 HIV-1（HIV）感染率最高的国家之一，年轻女性的感染率最高。我们分析了南非农村地区高中女生 HIV 的分子流行病学和进化史。
样本来自 HPTN 068 随机对照试验，该试验评估了向 13-20 岁女性提供上学补助金对 HIV 发病率的影响（Mpumalanga 省，2011-2015 年）。对感染 HIV 的参与者的血浆样本进行了 ViroSeq HIV-1 基因分型分析。使用来自南非的 200 个 pol 基因研究序列和 2294 个亚型 C 参考序列进行了系统发育分析。使用 Cluster Picker 和 HIV-TRACE 确定了传播簇，并使用人口统计学和其他流行病学数据对其进行了特征描述。使用 BEAST 软件进行了系统发育分析。
该研究纳入了 2533 名预计完成高中学业的年轻女性（主要研究）；部分参与者接受了学业后评估（随访研究）。2533 名入组的年轻女性中，有 212 人 HIV 感染。对 212 名 HIV 感染的参与者中的 94%（n=201）获得了 HIV pol 序列。除了一个序列外，所有序列均为 HIV-1 亚型 C；非 C 亚型序列被排除在进一步分析之外。亚型 C 序列之间的中位遗传距离为 6.4%（IQR：5.6-7.2）。总体而言，26%的研究序列分为 21 个进化簇，每个簇有 2-6 名女性。13 个（62%）簇包括在入组时感染 HIV 的女性。聚类与研究臂、人口统计学或其他流行病学因素无关。研究人群中 HIV 亚型 C 的估计起源日期为 1958 年（95%最高后验密度[HPD]：1931-1980 年），研究 pol 序列中估计的中位替代率为每年每个位点 1.98x10-3（95%HPD：1.15x10-3-2.81x10-3）。
系统发育分析表明，南非学龄女孩中存在多种 HIV 亚型 C 亚谱系。在 HPTN 068 试验中，对照组和干预组之间的 HIV 分子流行病学没有实质性差异。
