Kalidasan V, Theva Das Kumitaa
Infectomics Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Malaysia.
Front Microbiol. 2020 Jan 31;11:46. doi: 10.3389/fmicb.2020.00046. eCollection 2020.
There is a continuous search for an HIV cure as the success of ART in blocking HIV replication and the role of CD4 T cells in HIV pathogenesis and immunity do not entirely eradicate HIV. The Berlin patient, who is virus-free, serves as the best model for a 'sterilizing cure' and many experts are trying to mimic this approach in other patients. Although failures were reported among Boston and Essen patients, the setbacks have provided valuable lessons to strengthen cure strategies. Following the Berlin patient, two more patients known as London and Düsseldorf patients might be the second and third person to be cured of HIV. In all the cases, the patients underwent chemotherapy regimen due to malignancy and hematopoietic stem cell transplantation (HSCT) which required matching donors for CCR5Δ32 mutation - an approach that may not always be feasible. The emergence of newer technologies, such as long-acting slow-effective release ART (LASER ART) and CRISPR/Cas9 could potentially overcome the barriers due to HIV latency and persistency and eliminate the need for CCR5Δ32 mutation donor. Appreciating the failure and success stories learned from these HIV breakthroughs would provide some insight for future HIV eradication and cure strategies.
由于抗逆转录病毒疗法(ART)在阻断HIV复制方面取得成功,以及CD4 T细胞在HIV发病机制和免疫中的作用,但仍无法完全根除HIV,因此人们一直在不断寻求治愈HIV的方法。“柏林病人”已无病毒,是“灭菌治愈”的最佳范例,许多专家正试图在其他患者身上模仿这种方法。尽管波士顿和埃森的患者治疗失败,但这些挫折为强化治愈策略提供了宝贵经验。继“柏林病人”之后,另外两名患者,即“伦敦病人”和“杜塞尔多夫病人 ”,可能成为第二例和第三例治愈HIV的患者。在所有这些病例中,患者因恶性肿瘤接受了化疗方案和造血干细胞移植(HSCT),而这需要与携带CCR5Δ32突变的供体相匹配——这种方法并非总是可行。长效缓释抗逆转录病毒疗法(LASER ART)和CRISPR/Cas9等新技术的出现,可能会克服HIV潜伏和持续存在所带来的障碍,不再需要携带CCR5Δ32突变的供体。了解这些HIV突破中的失败与成功案例,将为未来的HIV根除和治愈策略提供一些启示。