新愛滋病毒豁免的「倫敦病人」提升了希望
資料來源：Heather Boerner, Medscape醫學新聞，2019年3月5日，財團法人台灣紅絲帶基金會編譯
西雅圖報導：一名倫敦男子在18個月以來一直沒有在他身體的系統中發現可檢測到的愛滋病毒，儘管他在此期間並沒有接受過愛滋治療。
患者在接受幹細胞移植後產生了病毒豁免。這使他成為歷史上的第二個人 – 在柏林患者之後 – 在移植後實現了HIV豁免。這也引發了人們對他是否可以達到愛滋病治癒的疑問。
倫敦大學學院的醫學博士Ravindra Gupta和他的團隊今天在 「自然」（Nature）雜誌線上發表的報告中寫道：「柏林病人不是一個異常現象」。
但Gupta表示，這不太可能導致感染愛滋病毒的人群進行廣泛的幹細胞移植手術，Gupta將於今天下午在反轉錄病毒和伺機性感染會議上討論此案。
他告訴Medscape醫學新聞，這只是「向正確方向邁出的一小步」。 「但只要累積足夠步數，我們就可以到達我們需要抵達的位置」。
除愛滋病毒外，柏林病人Timothy Brown和新病人（被稱為倫敦病人）都患有急性癌症，需要進行幹細胞移植，這是一種在其他治療方法失敗後使用的痛苦和侵入性的治療方法。
對於布朗來說，這是白血病。對於倫敦患者來說，這是第4階段的霍奇金氏淋巴瘤，這是一種在愛滋病毒感染者中更為常見但非屬愛滋病相關的癌症，。
兩名患者的幹細胞捐贈者都具有從CD4 T細胞表面除去CCR5受體的兩臂基因突變的幹細胞。沒有這種受體，大多數愛滋病毒株因不能進入細胞而無法造成傳播，並且 – 賓果 – 這就是愛滋病毒的終結。
倫敦病人
這些幹細胞移植和癌症治療通常建立一個可以對HIV產生敵意的獨特環境中。
首先，化學療法破壞了免疫系統，基本上消滅了許多HIV潛藏的貯藏窩，它們已準備好在治療停止時再度複製和再感染人。第二，新的幹細胞不會呈現CCR5移植到人體已被大量毀滅的免疫系統上。
「供體的組織成為你的組織」，Gupta解釋說。
「如果化學療法消除了貯藏窩，如果癌症沒有恢復，如果捐贈者新的組織是以具對抗HIV能力之細胞重新填充免疫系統，則病毒豁免的可能性非常高」。”
當Gupta的團隊開始他們的研究時，根據轉介病人的血液學家之建議，他們並沒有太大的希望它會起作用。倒不是因為所有的這些因素都不正確，而是因為有很多事情都可能出錯。
「我認為或者是癌症會復發，抑或是他會因為另一個原因而導致病毒反彈，你不要過於樂觀」 ，Gupta說道。 「但是暗地裡我對前景感到非常地興奮」。
看著和等待
隨著移植日期的臨近，研究小組繼續測試人體細胞中潛藏愛滋病毒的儲藏窩之情況，觀察化療摧毀了各處的免疫細胞。當他們找到幹細胞捐贈者時，他們很高興地發現，患者之最佳匹配的捐贈者也恰好在兩臂上都有基因的突變，可以去除CCR5受體。
The ‘London Patient’ New HIV Remission Raises Hope
Heather Boerner; March 05, 2019,Medscape Medical News
SEATTLE — A London man has not had detectable HIV in his system for 18 months, despite not having received treatment during that period.
The remission came after the patient underwent a stem cell transplant. This makes him the second man in history — after the Berlin patient — to have achieved HIV remission after such a transplant. And that has raised questions about whether he might be cured of HIV.
“The Berlin patient was not an anomaly,” Ravindra Gupta, MD, from University College London, and his team write in their report published online today in Nature.
But it is unlikely that this will lead to widespread stem cell transplants for people infected with HIV, said Gupta, who will discuss the case this afternoon here at the Conference on Retroviruses and Opportunistic Infections 2019.
It is only “a small step in the right direction,” he told Medscape Medical News. “But with enough small steps, we can get where we need to be.”
As well as HIV, both Berlin patient Timothy Brown and the new patient — referred to as the London patient — had acute cancers that called for a stem cell transplant, a painful and invasive treatment used after other treatments have failed.
For Brown, it was leukemia. For the London patient, it was stage 4 Hodgkin’s lymphoma, a non-AIDS-related cancer more common among people with HIV.
Both patients also had stem cell donors with two genetic mutations that remove the CCR5 receptor from the surface of the CD4 T-cell. Without that receptor, most HIV strains can’t gain access to the cell and can’t spread, and — bingo — that’s the end of HIV.
The London Patient
These stem cell transplants and cancer treatments in general set up a unique environment that can be hostile to HIV.
First, the chemotherapy destroys the immune system, essentially wiping out many of the reservoirs where HIV hides, ready to replicate and reinfect the person when treatment stops. And second, new stem cells that do not express CCR5 graft on to the person’s decimated immune system.
“The donor tissue becomes your tissue,” Gupta explained.
If the chemo eliminates reservoirs, if the cancer doesn’t come back, and if the new donor tissue repopulates the immune system with HIV-resistant cells, “the chances of remission are very good.”
When Gupta’s team began their study, at the suggestion of a referring hematologist, they didn’t have much hope it would work. Not because all those factors aren’t true, but because so many things can go wrong.
“I thought either the cancer would come back or he’d rebound for another reason. You’re trying not to be too optimistic,” said Gupta. “But secretly I was fairly excited about the prospects.”
Watching and Waiting
As the transplant date neared, the team continued to test the man’s cells for reservoirs of HIV, watching as the chemotherapy laid waste to immune cells everywhere. When they found a stem cell donor, they were pleased to discover that the best match for the patient also happened to have the genetic mutation on both arms that removed the CCR5 receptors.