Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario; Department of Medicine, University of Toronto, Ontario.
Department of Ecosystems and Public Health, Faculty of Veterinary Medicine.
Open Forum Infect Dis. 2015 Dec 23;3(1):ofv209. doi: 10.1093/ofid/ofv209. eCollection 2016 Jan.
Background. Seronegative human immunodeficiency virus (HIV) infections are exceedingly rare but might inform HIV-host physiology. Methods. We investigate the cause and consequences of a patient infected with HIV who did not mount a humoral response to HIV for 4 years. Results. The patient was confirmed HIV-uninfected by nucleic acid testing 4 months before rapidly progressing to acquired immune deficiency syndrome. The patient's humoral deficit was specific to HIV: he mounted robust humoral responses to all challenge vaccines including influenza A(H1N1)pdm09 and all T cell-dependent and -independent serotypes in the 23-valent pneumococcal polysaccharide vaccine. The virus had similar gp120 antigenicity to HIV-positive control serum as NL4-3 and YU2 prototype strains. Two human leukocyte antigen alleles associated with rapid progression were identified (B08 and B35), and a cytotoxic T-lymphocyte epitope site variant was noted: E277K. Viral decay (t 1/2 ≈ 39 weeks) suggested that relatively long-lived cells were the source of ongoing viremia. Human immunodeficiency virus viremia was not suppressed until after the patient developed a humoral immune response, despite therapeutic antiretroviral levels. No resistance was detected by virtual phenotyping of virus obtained from serum or from gastrointestinal biopsies despite considerable antiretroviral selection pressure. Conclusions. Ineffective antibody production may be associated with a subgroup of extremely rapid HIV progressors. Although antiretroviral therapy may be sufficient to slow propagation of infection, it appears to be ineffective for HIV viral clearance in the absence of a humoral response.
血清学阴性的人类免疫缺陷病毒（HIV）感染极其罕见，但可能提示 HIV 宿主的生理状态。
我们调查了一位感染 HIV 但在 4 年内未产生体液免疫反应的患者的病因和后果。
该患者在迅速进展为获得性免疫缺陷综合征前 4 个月，通过核酸检测确认 HIV 未感染。该患者的体液缺陷是 HIV 特异性的：他对所有挑战疫苗均产生了强烈的体液反应，包括流感 A（H1N1）pdm09 和 23 价肺炎球菌多糖疫苗中的所有 T 细胞依赖性和非依赖性血清型。该病毒与 HIV 阳性对照血清的 gp120 抗原性相似，与 NL4-3 和 YU2 原型株相似。鉴定出两个与快速进展相关的人类白细胞抗原等位基因（B08 和 B35），并注意到一个细胞毒性 T 淋巴细胞表位变异：E277K。病毒衰减（t 1/2≈39 周）表明，相对长寿的细胞是持续病毒血症的来源。尽管治疗性抗逆转录病毒水平很高，但在患者产生体液免疫反应之前，HIV 病毒血症并未得到抑制。尽管存在相当大的抗逆转录病毒选择压力，但从血清或胃肠道活检中获得的病毒的虚拟表型分析未检测到耐药性。
无效的抗体产生可能与极少数极快速 HIV 进展者有关。尽管抗逆转录病毒疗法可能足以减缓感染的传播，但在缺乏体液免疫反应的情况下，似乎对 HIV 病毒清除无效。
