Bautista-Amorocho Henry, Silva-Sayago Jorge Alexander, Picón-Villamizar Jirehl
Grupo de Investigación en Manejo Clínico CliniUDES, Facultad de Ciencias de la Salud, Universidad de Santander, Bucaramanga, Colombia.
Front Microbiol. 2023 Jul 24;14:1202342. doi: 10.3389/fmicb.2023.1202342. eCollection 2023.
Hepatitis B virus (HBV) antiviral Resistance-Associated Mutations (RAMs) in human immunodeficiency virus (HIV) coinfected patients undergoing highly active antiretroviral therapy (HAART) are complex and incompletely understood. We aimed to determine the prevalence of HBV coinfection, HBV genotypes, and RAMs in a cohort of people living with HIV (PLWH) in the northeastern region of Colombia. This cross-sectional study was carried out between February 2013 and February 2014. Virological, immunological and HAART data were collected from clinical records. In-house nested PCR and Sanger sequencing of the HBV gene were used to identify coinfections, genotypes, RAMs and HBV s antigen (HBsAg) escape mutants. Among 275 PLWH, HBV coinfection was confirmed in 32 patients (11.6%), of whom nine (28.2%) were HBsAg positive (active hepatitis B), and 23 (71.8%) were occult hepatitis B infections (OBI). All HBV sequences (n = 23) belonged to the genotype F3. Among HIV/HBV coinfections, 71.9% had CD4+ T cell counts above 200 cells/mm and 37.5% had undetectable HIV viral loads. The RAMs rtL80I, rtL180M, and rtM204V, which confer resistance to Lamivudine/Telbivudine and partially resistant to Entecavir, were found in all HBV isolates. An unknown rt236Y mutation to Tenofovir was also identified. Most patients under HAART received first-generation HBV antiviral therapy with a low genetic barrier to resistance. Antiviral Drug-associated Potential Vaccine-escape Mutations (ADAPVEMs) in the gene were observed in all isolates ranging from 1-20 amino acid substitutions. However, no vaccine escape mutants were detected. In Conclusion, these findings highlight the importance of HBV molecular screening, antiviral resistance monitoring and new guidelines for PLWH to overcome RAMs and prevent HBV-related liver disease.
在接受高效抗逆转录病毒疗法（HAART）的人类免疫缺陷病毒（HIV）合并感染患者中，乙型肝炎病毒（HBV）抗病毒耐药相关突变（RAMs）情况复杂，尚未完全明确。我们旨在确定哥伦比亚东北部地区一组艾滋病毒感染者（PLWH）中HBV合并感染率、HBV基因型及RAMs情况。这项横断面研究于2013年2月至2014年2月进行。从临床记录中收集病毒学、免疫学及HAART数据。采用内部巢式PCR及HBV基因的桑格测序法来鉴定合并感染、基因型、RAMs及HBV表面抗原（HBsAg）逃逸突变体。在275例PLWH中，32例（11.6%）确诊为HBV合并感染，其中9例（28.2%）HBsAg阳性（活动性乙型肝炎），23例（71.8%）为隐匿性乙型肝炎感染（OBI）。所有HBV序列（n = 23）均属于F3基因型。在HIV/HBV合并感染患者中，71.9%的CD4 + T细胞计数高于200个细胞/mm³，37.5%的HIV病毒载量检测不到。在所有HBV分离株中均发现了对拉米夫定/替比夫定耐药且对恩替卡韦部分耐药的RAMs rtL80I、rtL180M和rtM204V。还鉴定出一种对替诺福韦未知的rt236Y突变。大多数接受HAART的患者接受的是第一代HBV抗病毒治疗，其耐药基因屏障较低。在所有分离株中均观察到基因中与抗病毒药物相关的潜在疫苗逃逸突变（ADAPVEMs），氨基酸替换范围为1 - 20个。然而，未检测到疫苗逃逸突变体。总之，这些发现凸显了对PLWH进行HBV分子筛查、抗病毒耐药监测以及制定新指南以克服RAMs并预防HBV相关肝病的重要性。
