新研究显示骨髓移植后第二例 HIV 成功缓解
每年至少有 35 万人死于与 HIV 相关的原因，近 XNUMX 万人患有 艾滋病毒. HIV-1（人类免疫缺陷病毒）是全世界大多数 HIV 感染的罪魁祸首，它通过直接接触 HIV 感染的体液传播。 病毒攻击并杀死我们免疫系统的关键抗感染细胞。 没有治愈艾滋病毒的方法。 目前，只能使用能够抑制 HIV 的药物来治疗 HIV 病毒. These drugs have to be taken life long and it is challenging plus a cost burden on the health system especially in low-and-middle-income countries. Only 59 percent of patients of HIV worldwide are receiving Antiretroviral therapy (ARV) and 艾滋病毒 virus is fast becoming resistant from many known drugs which itself is a major concern.
骨髓移植 (BMT) is a treatment used for leukemia, myeloma, lymphoma etc. Bone marrow, the soft tissue inside bones, makes blood-forming cells including the infection fighting white blood cells. A bone marrow transplant replaces unhealthy marrow with a healthy one. In the first case of successful 艾滋病毒 remission, an 艾滋病毒-infected individual called ‘Berlin Patient’ who later revealed his name received a bone marrow transplant a decade ago when he was targeted to treat acute leukemia. He received two transplants along with total body irradiation which led to long-term 艾滋病毒 缓解。
在发表于 自然 led by UCL and Imperial College London, the only second person has been shown to experience sustained remission from HIV-1 after a bone marrow transplant and stoppage of treatment. The anonymous adult male patient from UK was diagnosed with HIV infection in 2003 and was on antiretroviral therapy treatment since 2012. He was subsequently diagnosed with Hodgkin’s Lymphoma in the same year and he underwent chemotherapy. In 2016, he was given stem cell transplant from a donor who carried a genetic mutation which prevents expression of a most commonly used 艾滋病毒 receptor protein called CCR5. Such a donor is resistant to HIV-1 strain of the virus which specifically uses CCR5 receptor and thus the virus now cannot enter host cells. Since chemotherapy kills cells which are dividing, 艾滋病毒 could be targeted. From this understanding if one’s immune cells are replaced by cells which do not have CCR5 receptor, 艾滋病毒 can be prevented from rebounding after the treatment.
移植手术的副作用很小，例如在移植手术中常见的轻微并发症，在移植手术中，受体的免疫细胞受到供体免疫细胞的攻击。 移植后继续抗逆转录病毒治疗 16 个月，然后决定停止治疗以评估 HIV-1 的缓解情况。 在此之后，患者的病毒载量仍然无法检测到。 由于患者的免疫细胞无法产生关键的 CCR18 受体，患者在抗逆转录病毒治疗中断 5 个月后仍处于缓解状态。 该总持续时间等于移植后的 35 个月。
This is a second case of a patient exhibiting sustained remission of 艾滋病毒-1 following a bone marrow transplant. One important difference in this second patient being that ‘Berlin Patient’ had received two transplants along with total body irradiation while this UK patient received only a single transplant and underwent less aggressive and lesser toxic approach of chemotherapy. Mild complications of similar nature were seen in both patients i.e. graft versus host disease. Achieving success in two different patients points towards developing strategies based on preventing CCR5 expression which might even cure 艾滋病毒.
Authors state that they are monitoring the patient’s condition and cannot say with affirmation yet if he has been cured of HIV. This may not be a generalized appropriate treatment for 艾滋病毒 because of adverse effects and toxicity of chemotherapy. Also, bone-marrow transplants are expensive and carry risks. Nevertheless, it is a better approach with reduced intensity conditioning and no irradiation. Research could also focus on knocking out the CCR5 receptor using gene therapy in people with 艾滋病毒.
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来源（S）
1. Gupta RK 等。 2019. CCR1Δ5/Δ32 造血干细胞移植后 HIV-32 缓解。 自然。 http://dx.doi.org/10.1038/s41586-019-1027-4
2. Hütter G. 等。 2009. 通过 CCR5 Delta32/Delta32 干细胞移植长期控制 HIV。 N Engl J Med。 360。 https://doi.org/10.1056/NEJMoa0802905
3. Brown TR 2015。我是柏林病人：个人反思，艾滋病研究和人类逆转录病毒。 31（1）。 https://doi.org/10.1089/aid.2014.0224
