Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
Genes (Basel). 2021 Aug 26;12(9):1314. doi: 10.3390/genes12091314.
Human immunodeficiency virus (HIV) drug resistance (HIVDR) is widespread in sub-Saharan Africa. Children and pregnant women are particularly vulnerable, and laboratory testing capacity remains limited. We, therefore, used a cross-sectional design and convenience sampling to characterize HIV subtypes and resistance-associated mutations (RAMs) in these groups in Sierra Leone. In total, 96 children (age 2-9 years, 100% ART-experienced), 47 adolescents (age 10-18 years, 100% ART-experienced), and 54 pregnant women (>18 years, 72% ART-experienced) were enrolled. Median treatment durations were 36, 84, and 3 months, respectively, while the sequencing success rates were 45%, 70%, and 59%, respectively, among children, adolescents, and pregnant women. Overall, the predominant HIV-1 subtype was CRF02_AG (87.9%, 95/108), with minority variants constituting 12%. Among children and adolescents, the most common RAMs were M184V (76.6%, = 49/64), K103N (45.3%, = 29/64), Y181C/V/I (28.1%, = 18/64), T215F/Y (25.0%, = 16/64), and V108I (18.8%, = 12/64). Among pregnant women, the most frequent RAMs were K103N (20.6%, = 7/34), M184V (11.8%, = 4/34), Y181C/V/I (5.9%, = 2/34), P225H (8.8%, = 3/34), and K219N/E/Q/R (5.9%, = 2/34). Protease and integrase inhibitor-RAMs were relatively few or absent. Based on the genotype susceptibility score distributions, 73%, 88%, and 14% of children, adolescents, and pregnant women, respectively, were not susceptible to all three drug components of the WHO preferred first-line regimens per 2018 guidelines. These findings suggest that routine HIVDR surveillance and access to better ART choices may improve treatment outcomes in Sierra Leone.
人类免疫缺陷病毒（HIV）耐药性（HIVDR）在撒哈拉以南非洲广泛存在。儿童和孕妇尤其容易受到影响，而实验室检测能力仍然有限。因此，我们采用横断面设计和方便抽样的方法，描述了塞拉利昂这些人群中的 HIV 亚型和耐药相关突变（RAMs）。共纳入 96 名儿童（2-9 岁，100%接受 ART 治疗）、47 名青少年（10-18 岁，100%接受 ART 治疗）和 54 名孕妇（>18 岁，72%接受 ART 治疗）。儿童、青少年和孕妇的中位治疗时间分别为 36、84 和 3 个月，测序成功率分别为 45%、70%和 59%。总体而言，HIV-1 主要亚型为 CRF02_AG（87.9%，95/108），少数变体占 12%。在儿童和青少年中，最常见的 RAM 是 M184V（76.6%，=49/64）、K103N（45.3%，=29/64）、Y181C/V/I（28.1%，=18/64）、T215F/Y（25.0%，=16/64）和 V108I（18.8%，=12/64）。在孕妇中，最常见的 RAM 是 K103N（20.6%，=7/34）、M184V（11.8%，=4/34）、Y181C/V/I（5.9%，=2/34）、P225H（8.8%，=3/34）和 K219N/E/Q/R（5.9%，=2/34）。蛋白酶和整合酶抑制剂 RAM 相对较少或不存在。根据基因型耐药评分分布，分别有 73%、88%和 14%的儿童、青少年和孕妇对世卫组织 2018 年首选一线方案的所有三种药物成分均不敏感。这些发现表明，在塞拉利昂，常规 HIVDR 监测和获得更好的 ART 选择可能会改善治疗结果。
