Ramos Belén, Núñez Marina, Martín-Carbonero Luz, Sheldon Julie, Rios Pilar, Labarga Pablo, Romero Miriam, Barreiro Pablo, García-Samaniego Javier, Soriano Vincent
Service of Infectious Diseases, Hospital Carlos III, Calle Sinesio Delgado 10, 28029 Madrid, Spain.
J Acquir Immune Defic Syndr. 2007 Apr 15;44(5):557-61. doi: 10.1097/QAI.0b013e3180314b46.
Differences in subtypes, hepatitis B early antigen (HBeAg)-negative variants, and drug resistance mutations all seem to influence the clinical and therapeutic outcome in patients with chronic hepatitis B virus (HBV) infection. Information available on the prevalence and distribution of distinct HBV variants in HIV-positive patients is scarce.
All HIV-infected patients with persistent serum hepatitis B surface antigen and detectable HBV viremia were identified in a reference HIV clinic located in Madrid, Spain. HBV load, subtypes, precore (PC) and basal core promoter (BCP) variants, and lamivudine (LAM) resistance mutations were analyzed.
A total of 81 HBV/HIV-coinfected patients (4.1%) were identified in a population of 1968 HIV-positive patients. Plasma specimens with detectable HBV viremia could be obtained from 62 subjects, and this was the study population that underwent further virologic characterization. HBV genotype distribution was as follows: A (n = 27), D (n = 27), E (n = 1), F (n = 2), and G (n = 3). Two patients had mixed HBV genotypes (A/E and A/F). HBV subtype A was predominant (74%) among patients infected through sexual contact, whereas HBV-D was most frequent (74%) among intravenous drug users (P < 0.001). PC/BCP mutants were more frequent in patients with HBV-D than in those with HBV-A (63% vs. 18%; P < 0.01). Median time on LAM was 40 months; patients with HBV-A tended to show LAM resistance mutations more often (53% vs. 44%) and to develop them earlier (35 vs. 45 months) than patients with HBV-D. The dual L180M + M204V/I mutant was the predominant resistance pattern, although a triple rt173V + 180M + 204V, which acts as a vaccine escape mutant, was found in 1 individual. In the multivariate analysis, patients with LAM resistance mutations were significantly more frequently HBeAg-positive and older than individuals with wild-type HBV. Hepatitis-delta was recognized in 13 (21%) of these 62 HBV viremic patients, with no association with specific HBV variants.
Risk transmission group, age, and positive serum HBeAg are the main determinants of distinct HBV virologic variants, including HBV genotypes and LAM-resistant mutants, in HBV/HIV-coinfected patients.
乙肝病毒（HBV）感染患者的亚型、乙肝e抗原（HBeAg）阴性变异体及耐药突变的差异似乎均会影响临床及治疗结果。关于HIV阳性患者中不同HBV变异体的流行率及分布情况的可用信息较少。
在西班牙马德里一家HIV专科门诊中，识别出所有持续性血清乙肝表面抗原阳性且可检测到HBV病毒血症的HIV感染患者。分析HBV载量、亚型、前核心（PC）及基本核心启动子（BCP）变异体以及拉米夫定（LAM）耐药突变情况。
在1968例HIV阳性患者中，共识别出81例HBV/HIV合并感染患者（4.1%）。可从62例受试者处获取可检测到HBV病毒血症的血浆样本，这62例受试者即为接受进一步病毒学特征分析的研究人群。HBV基因型分布如下：A（n = 27）、D（n = 27）、E（n = 1）、F（n = 2）及G（n = 3）。2例患者存在混合HBV基因型（A/E和A/F）。通过性接触感染的患者中，HBV A亚型占主导（74%），而在静脉吸毒者中，HBV D型最为常见（74%）（P < 0.001）。HBV D型患者中PC/BCP突变体比HBV A型患者更常见（63%对18%；P < 0.01）。接受LAM治疗的中位时间为40个月；与HBV D型患者相比，HBV A型患者更易出现LAM耐药突变（53%对44%）且出现时间更早（35个月对45个月）。双突变L180M + M204V/I是主要的耐药模式，不过在1例患者中发现了作为疫苗逃逸突变体的三重突变rt173V + 180M + 204V。多因素分析显示，与野生型HBV患者相比，存在LAM耐药突变的患者HBeAg阳性及年龄较大的比例显著更高。在这62例HBV病毒血症患者中，13例（21%）检测出丁型肝炎，与特定HBV变异体无关联。
在HBV/HIV合并感染患者中，风险传播组、年龄及血清HBeAg阳性是包括HBV基因型及LAM耐药突变体在内的不同HBV病毒学变异体的主要决定因素。
