人类免疫缺陷病毒（HIV）耐药性、系统发生分析以及撒哈拉以南非洲男男性行为者和跨性别女性中的再感染：HIV 预防试验网络（HPTN）075 研究。
Human Immunodeficiency Virus (HIV) Drug Resistance, Phylogenetic Analysis, and Superinfection Among Men Who Have Sex with Men and Transgender Women in Sub-Saharan Africa: HIV Prevention Trials Network (HPTN) 075 Study.
机构信息
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
出版信息
Clin Infect Dis. 2021 Jul 1;73(1):60-67. doi: 10.1093/cid/ciaa1136.
BACKGROUND
The HIV Prevention Trials Network (HPTN) 075 study evaluated the feasibility of enrolling and retaining men who have sex with men (MSM) and transgender women (TGW) from Kenya, Malawi, and South Africa. During the study follow-up, 21 participants acquired human immunodeficiency virus (HIV) (seroconverters). We analyzed HIV subtype diversity, drug resistance, transmission dynamics, and HIV superinfection data among MSM and TGW enrolled in HPTN 075.
METHODS
HIV genotyping and drug resistance testing were performed for participants living with HIV who had viral loads >400 copies/mL at screening (prevalent cases, n = 124) and seroconverters (n = 21). HIV pol clusters were identified using Cluster Picker. Superinfection was assessed by a longitudinal analysis of env and pol sequences generated by next-generation sequencing.
RESULTS
HIV genotyping was successful for 123/124 prevalent cases and all 21 seroconverters. The major HIV subtypes were A1 (Kenya) and C (Malawi and South Africa). Major drug resistance mutations were detected in samples from 21 (14.6%) of 144 participants; the most frequent mutations were K103N and M184V/I. Phylogenetic analyses identified 11 clusters (2-6 individuals). Clusters included seroconverters only (n = 1), prevalent cases and seroconverters (n = 4), and prevalent cases only (n = 6). Superinfections were identified in 1 prevalent case and 2 seroconverters. The annual incidence of superinfection was higher among seroconverters than among prevalent cases, and was higher than the rate of primary HIV infection in the cohort.
CONCLUSIONS
This report provides important insights into HIV genetic diversity, drug resistance, and superinfection among MSM and TGW in sub-Saharan Africa. These findings may help to inform future HIV prevention interventions in these high-risk groups.
背景
HIV 预防试验网络（HPTN）075 研究评估了从肯尼亚、马拉维和南非招募和保留男男性行为者（MSM）和跨性别女性（TGW）的可行性。在研究随访期间，有 21 名参与者感染了人类免疫缺陷病毒（HIV）（血清转换者）。我们分析了 HPTN 075 中招募的 MSM 和 TGW 中的 HIV 亚型多样性、耐药性、传播动力学和 HIV 超感染数据。
方法
对筛查时病毒载量>400 拷贝/ml 的 HIV 感染者（现患病例，n=124）和血清转换者（n=21）进行 HIV 基因分型和耐药性检测。使用 Cluster Picker 鉴定 HIV pol 簇。通过对下一代测序生成的 env 和 pol 序列进行纵向分析来评估超感染。
结果
123/124 例现患病例和 21 例血清转换者的 HIV 基因分型均成功。主要 HIV 亚型为 A1（肯尼亚）和 C（马拉维和南非）。在 144 名参与者中有 21 名（14.6%）的样本中检测到主要耐药突变；最常见的突变是 K103N 和 M184V/I。系统进化分析鉴定了 11 个簇（2-6 人）。簇包括仅血清转换者（n=1）、现患病例和血清转换者（n=4）以及仅现患病例（n=6）。在 1 例现患病例和 2 例血清转换者中发现了超感染。血清转换者的超感染年发生率高于现患病例，高于队列中的原发性 HIV 感染率。
结论
本报告提供了撒哈拉以南非洲地区 MSM 和 TGW 中 HIV 遗传多样性、耐药性和超感染的重要见解。这些发现可能有助于为这些高危人群提供未来的 HIV 预防干预措施。
Zotero 插件