大型新研究顯示,愛滋病毒藥物可能有助於預防多發性硬化症

資料來源:凱拉·麥凱 (Kyla McKay) 和伊萊恩·金威爾 (Elaine Kingwell) / 2023 年 12 月 20 日 / The Conversation

凱拉·麥凱,卡羅林斯卡學院神經流行病學助理教授

在過去的十年中,一些案例研究報告稱,多發性硬化症(MS) 患者開始接受HIV 抗反轉錄病毒治療(以控制病毒),隨後發現他們的多發性硬化症症狀要麼完全消失,要麼疾病進展明顯減慢。
這些發現迫使研究人員詢問愛滋病毒或抗病毒藥物是否會影響多發性硬化症的風險。 根據我們發表在《神經病學年鑑》上的最新研究,答案是肯定的。
很難確定愛滋病毒或抗反轉錄病毒藥物是否會影響多發性硬化症,因為必須對大量愛滋病毒感染者進行長期跟踪,並掌握有關愛滋病毒和多發性硬化症的詳細醫療資訊。
先前有三項研究提出了這個問題,但要麼患者太少,要麼無法獲得抗反轉錄病毒治療的資訊。 因此,早期的研究尚未提供明確的答案。
在這項研究中,我們使用了基於人口的大型健康資料庫以及臨床 HIV 和 MS 登記處。 他們幾乎包括了自 1992 年加拿大不列顛哥倫比亞省和和自 2001 年以來瑞典在醫學上被認定為愛滋病毒陽性的所有人。
我們從愛滋病毒感染者首次被識別之日起一直追蹤到研究期結束(加拿大為 2020 年,瑞典為 2018 年)。 使用醫院和醫生的數據以及從多發性硬化症專科診所獲取的資訊來搜尋這段時期新的多發性硬化症診斷。
將愛滋病毒感染者中新發多發性硬化症病例的比率與每個地區一般人群中新發病例的比率進行比較,以確定愛滋病毒感染者中是否確實存在不同的多發性硬化症風險。
我們識別了超過 29,000 名愛滋病毒感染者,並對他們進行了平均近十年的追蹤調查。 在此期間,只有 14 名 HIV 呈陽性的人患上了多發性硬化症,這比根據普通人群的預期病例數少了 47%。
當我們專門觀察服用抗反轉錄病毒藥物的人(幾乎研究中的所有人),並且僅在他們開始抗反轉錄病毒治療後,我們發現多發性硬化症病例比預期減少了 45%。 換句話說,我們發現愛滋病毒呈陽性並接受過抗反轉錄病毒治療的人的風險降低了。
女性罹患多發性硬化症的風險顯著降低,降低了 72%。 愛滋病毒感染者患有多發性硬化症的男性人數也比預期少,但男性的風險差異不如女性明顯。
可能的生物學解釋
僅從這項研究的結果來看,無法判斷病毒或抗病毒治療是否導致多發性硬化症風險降低。 然而,有生物學原因支持這兩種理論。
HIV 會導致稱為 CD4+ T 細胞的免疫細胞逐漸喪失。 這些相同的細胞與多發性硬化症有關,因為它們引發了一系列事件,導致大腦和脊髓發炎。 透過減少 CD4+ T 細胞數量,感染 HIV 可以降低一個人患 MS 的可能性。
不過,當 HIV 病毒被抗病毒藥物抑制時,多發性硬化症的風險就會降低,這項發現可能會帶來一些希望,即是治療而不是病毒發揮了作用。
抗反轉錄病毒藥物降低多發性硬化症風險和殘疾的可能機制包括抑制 Epstein-Barr 病毒[人類疱疹病毒第四型(Human herpesvirus 4,HHV-4)或稱EB病毒]。 越來越多的研究正在強調 EB病毒在多發性硬化症中的重要角色。
HIV 療法的抗病毒特性可能會限制 Epstein-Barr 病毒的活性,從而最大限度地降低多發性硬化症和疾病進展的風險。
HIV 感染或抗病毒藥物對多發性硬化症具有保護作用的發現有可能擴大我們對多發性硬化症原因以及該疾病如何損害身體的了解。
儘管對於復發型多發性硬化症有多種治療方法,但沒有一種方法可以阻止疾病後期的持續進展。 這項研究的結果可能會鼓勵大家更努力地確定抗反轉錄病毒藥物是否可以減緩多發性硬化症的進展。
在研究資源有限的情況下,這種方法可以產生更直接的效益,解決開發更好的治療方法以預防或減緩多發性硬化症進展上的主要未被滿足亡需求。
揭露聲明
凱拉·麥凱 (Kyla McKay) 獲得了瑞典健康、工作生活和福利研究委員會以及 StratNeuro 的研究資助。
伊萊恩·金威爾 (Elaine Kingwell) 獲得了加拿大健康研究所和加拿大 MS 的資助。
HIV drugs might help prevent multiple sclerosis, large new study suggests
Kyla McKay & Elaine Kingwell / December 20, 2023 / The Conversation
Kyla McKay, Assistant Professor of Neuroepidemiology, Karolinska Institutet

Elaine Kingwell, Senior Research Fellow, Primary Care and Population Health, UCL
Over the last decade, several case studies have reported that people with multiple sclerosis (MS) who started antiretroviral therapy for HIV (to keep the virus in check) subsequently found that their MS symptoms had either disappeared completely or the disease progression had slowed considerably.
These findings compelled researchers to ask whether HIV or antiretrovirals could influence the risk of developing MS. According to our latest study, published in Annals of Neurology, the answer is yes.
It’s very difficult to be certain if HIV or antiretroviral drugs might affect MS because large groups of people living with HIV, with detailed medical information on both HIV and MS, must be followed for a long period.
Three studies previously asked this question but had either too few patients or no access to information on antiretroviral treatment. Consequently, earlier studies have not provided definitive answers.
For this study, we used large population-based health databases and clinical HIV and MS registries. They included virtually every person in British Columbia, Canada and Sweden who was medically recognised as HIV-positive dating back to 1992 in Canada and 2001 in Sweden.
We followed people with HIV from the first date that their HIV infection was recognised until the end of the study period (2020 in Canada and 2018 in Sweden). New diagnoses of MS during this period were searched for using data from hospitals and doctors, as well as information captured from specialist MS clinics.
The rate of new MS cases among people with HIV was compared to the rate of new cases in the general population within each region to determine if there truly was a different risk of MS in people with HIV.
We identified over 29,000 people with HIV and followed them for an average of nearly ten years. Over this period, only 14 HIV-positive people developed MS, which was 47% fewer cases than expected based on numbers in the general population.
When we looked specifically at people who had taken antiretroviral drugs (nearly everyone in the study), and only after they started antiretroviral therapy, we found 45% fewer MS cases than expected. In other words, we found a reduced risk among people who were HIV-positive and had used antiretroviral therapy.
The risk of MS was most significantly reduced for women, with a reduction of 72%. There were also fewer men developing MS in the HIV population than expected, but the difference in risk was less pronounced in men than in women.
Possible biological explanation
From the results of this study alone, it is not possible to tell whether the virus or the antiretroviral therapy might be responsible for the reduction in MS risk. However, there are biological reasons to support both theories.
HIV leads to a progressive loss of immune cells called CD4+ T cells. These same cells are implicated in MS, as they initiate the cascade of events that leads to inflammation of the brain and spinal cord. By reducing CD4+ T cell counts, infection with HIV could reduce the likelihood of a person developing MS.
The finding that MS risk was lower when the HIV virus is presumably suppressed by antiretroviral drugs, though, might offer some hope that it is the treatment rather than the virus that plays a role.
Possible mechanisms for the effectiveness of antiretrovirals in reducing MS risk and disability include the inhibition of the Epstein-Barr virus. More and more research is accumulating to highlight the important role of Epstein-Barr in MS.
The antiviral properties of HIV therapy might limit Epstein-Barr virus activity, thereby minimising both the risk of getting MS and of the disease progressing in those who have it.
The finding that HIV infection or antiretrovirals confer a protective effect against MS holds the potential to broaden our understanding of the causes of MS and how the disease damages the body.
Although treatments are available for the relapsing form of MS, none can halt the persistent progression seen later in the disease. Findings from this study might encourage a more concerted effort to determine whether antiretroviral drugs could slow MS disease progression.
With limited research resources, this approach could yield a more immediate benefit, addressing the major unmet need to develop better treatments aimed at preventing or slowing the progression of MS.
Disclosure statement
Kyla McKay has received research funding from the Swedish Research Council for Health, Workling Life and Welfare and StratNeuro.
Elaine Kingwell has received funding from the Canadian Institutes of Health Research and MS Canada.