METHODS: Homozygousity for the p.His63Asp (H63D) variant in the HFE gene was identified in an 80-year-old HIV-infected woman with spontaneous control of viral replication.
METHODS: HIV-1 RNA was undetectable in patient\'s serum with a routine assay and an ultra-sensitive assay (<1 copy/mL) during the 30 years follow-up. CD4+ and CD8+ T cell counts were stable and normal during all this period.
METHODS: The patient had a history of absence of any physical ailment and no antiviral therapy has been prescribed during the 30 years of follow-up. The subject did not harbor HLA-B∗57 and HLA-B∗27 alleles. HFE gene was sequenced by Sanger, as part of a larger study on a cohort of HIV infected patients, aged >65 years and screened for polymorphisms in genes belonging to several pathways involved in neuroinflammation.
RESULTS: The woman had CD4+ and CD8+ T cell normal values and spontaneously controlled serum HIV-1 RNA levels for 30 years.
CONCLUSIONS: We assume that the interplay between the HFE H63D variant in homozygosity and innate immunity, perhaps through autophagy regulation, could play a role in HIV-1 replication control in our patient. This hypothesis needs to be explored in in vitro and in vivo studies. Understanding mechanisms involved in spontaneous control of HIV-1 replication remains indeed a challenge due to its possible implications for HIV cure research.
方法:在一名80岁感染HIV的女性中鉴定了HFE基因中p.His63Asp(H63D)变体的纯合性,该女性自发控制了病毒复制。
方法:在30年的随访中,常规检测和超敏感检测(<1拷贝/mL)在患者血清中检测不到HIV-1RNA。CD4+和CD8+T细胞计数在这期间是稳定和正常的。
方法:患者有没有任何身体疾病的病史,在30年的随访中没有规定抗病毒治疗。受试者未携带HLA-B*57和HLA-B*27等位基因。由Sanger对HFE基因进行测序,作为对HIV感染患者队列的更大研究的一部分,年龄>65岁,并筛选了涉及神经炎症的几种途径的基因多态性。
结果:该女性具有30年的CD4+和CD8+T细胞正常值和自发控制的血清HIV-1RNA水平。
结论:我们假设HFEH63D变体在纯合性和先天免疫之间的相互作用,也许通过自噬调节,可以在我们患者的HIV-1复制控制中发挥作用。这一假设需要在体外和体内研究中进行探索。理解HIV-1复制的自发控制机制仍然是一个挑战,因为它可能对HIV治愈研究产生影响。