HIV感染真的被“治愈”了吗?

Is HIV Infection Really Cured?

人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染靶细胞需要识别细胞表面CD4分子及其辅助受体,C-C趋化因子受体5 (C-C chemokine receptor type 5,CCR5)和C-X-C趋化因子受体4 (C-X-C-motif receptor 4,CXCR4)是HIV识别靶细胞的两种重要辅助受体。CCR5Δ32基因突变使得HIV无法识别CCR5受体,从而阻止嗜CCR5的HIV病毒株入侵靶细胞。"柏林病人"和"伦敦病人"正是利用这一原理,通过移植携带纯合子CCR5Δ32突变基因的异基因骨髓,实现了停用抗病毒药物后病毒无反弹的目标,故而被誉为HIV感染"治愈"案例。然而,这一成功是否存在偶然性?事实上,人群中携带CCR5Δ32纯合子基因突变概率极低、异基因骨髓配型十分困难、骨髓移植医疗费用昂贵、移植后HIV病毒株嗜性迁移等客观因素的存在,使得通过携带纯合子CCR5Δ32基因突变异基因骨髓移植法实现HIV感染者停用抗病毒药物且保持病毒不反弹的目标困难重重。因此,"柏林病人"和"伦敦病人"的成功经验为治疗HIV感染提供了新的方向和希望,但如认为HIV感染已被"治愈"为时尚早,需进一步研究证实。

Infection with the human immunodeficiency virus (HIV) requires the presence of CD4 receptors and chemokine receptors. Two of the most principal chemokine receptors are C-C chemokine receptor 5 (CCR5) and/or the chemokine (C-X-C motif) receptor 4 (CXCR4). Homozygosity of a 32-bp deletion in the CCR5 allele provides resistance against the cellular entry of CCR5-tropic HIV strains. The successful long-term control of HIV by allogeneic haematopoietic stem cell transplantations (allo-HSCT) from a donor who was homozygous for CCR5 delta32, had been documented as a “Berlin patient” and a “London patient”. They both had remained without viral recrudescence after transplantation and discontinuation of antiretroviral therapy. However, a wide application of allo-HSCT from donors with homozygous CCR5 delta32 mutation for HIV remission is still quite challenging so far under the condition of a low percentage of homozygous CCR5 delta32 mutation, high risk of allo-HSCT, HIV tropism shift after HSCT, and huge expense. Although the “Berlin patient” and the “London patient” take a new hope to control HIV infection, it is still too early to conclude that the “cure” of HIV infection has been achieved.