HIV很快就能治癒嗎？新療法帶來希望
Barbara Zenz / 2025年10月15日 / Medscape 醫學新聞
1981年，洛杉磯的醫生報告了五名患有肺囊蟲肺炎的年輕患者。這種罕見的肺部感染後來被認為是 HIV 感染的首發症狀，也是愛滋病的典型症狀。
當時，臨床醫師們對此感到困惑。伺機性感染通常只發生在嚴重免疫抑制的個體；然而，其病因—HIV—仍未知。
這種疾病很快就在全球蔓延，並成為一種流行病，直到1987年第一種有效的抗反轉錄病毒藥物齊多夫定zidovudine（疊氮胸苷 ，azidothymidine）問世。
經過40多年的研究，HIV 感染被認為是一種可控制的慢性疾病，而非致命的疾病。透過綜合抗反轉錄病毒療法 (ART)，HIV 感染者可以過著正常的生活，並且在病毒量檢測不到的情況下不會透過性傳播病毒。
儘管取得了這些進展，並經過數十年的深入研究，但這種疾病仍然無法治癒。除少數例外，所有永久清除體內病毒的努力均告失敗。
這主要是因為HIV-1和更罕見的HIV-2基因變異性極高，並且在很大程度上逃避了人體免疫系統的攻擊。因此，要透過清除病毒來實現持續緩解或治癒，需要多樣化的策略、堅持不懈的努力以及大量的反覆試驗。
法國研究人員在《刺胳針愛滋病》雜誌上發表的一篇文章中提醒醫學界，愛滋病毒是有可能治癒的。該篇文章呼籲在全球愛滋病毒治療費用削減的情況下，借鑒以往的成功經驗，優先考慮治癒性療法。
儘管採取了有效的治療方法和預防策略，但全球仍有63萬人死於愛滋病相關疾病，4,080萬人感染愛滋病毒，另有130萬人新感染。作者認為，這些數字凸顯了對治癒性療法的迫切需求。如果沒有足夠的資金，到2030年之前的進展可能會付諸東流，而如果沒有治癒方法，這場大流行就無法結束。
本文的共同作者、法國諾貝爾獎得主弗朗索瓦絲·巴爾-西諾西 (Françoise Barré-Sinoussi) 於20世紀70年代初在巴黎巴斯德研究所開始研究反轉錄病毒，後來領導了該研究所的「反轉錄病毒感染調控」部門。
她於1983年領導的論文首次將HIV確定為愛滋病的病因，由於共同作者威利·羅森鮑姆 (Willy Rozenbaum) 的努力，該論文現已免費開放。巴爾-西諾西和呂克·蒙塔尼耶 (Luc Montagnier) 因發現該病毒而獲得了2008年諾貝爾生理學或醫學獎。
HIV治療經歷了幾個轉折點，顯著提高了患者照護的品質。關鍵的里程碑包括抗反轉錄病毒療法 (ART) 的開發、HIV暴露前預防 (PrEP) 的引入以及多藥製成單錠療法的出現。近年來，注射針劑和長效療法拓展了治療和預防的選擇。
PrEP 的突破
儘管取得了這些進展，但愛滋病毒感染仍然是全球健康問題。低門檻以獲得抗反轉錄病毒療法 (ART) 和 PrEP 等藥物的途徑仍遠未普及，但它們在未來幾年顯著減少新的感染、愛滋病相關疾病的發病率以及愛滋病相關死亡上至關重要。
污名化和歧視持續導致人們迴避社交和治療，尤其是在受影響最嚴重的國家。
依從性差也會增加對常見愛滋病毒藥物（例如多替拉韋，dolutegravir）產生抗藥性的風險，尤其是在因成本原因而導致抗藥性檢測受限的情況下。
長效愛滋病毒療法已被開發出來以克服這些挑戰。自 2020 年以來，首個注射用 HIV 整合酶抑制劑卡博特韋 (cabotegravir) 已成為每日口服抗病毒療法的替代方案。
經過28天的口服誘導期以確定不耐受之情況後，患者接受單次初始劑量600毫克卡博特韋(cabotegravir) 和900毫克利匹韋林 (rilpivirine) 肌肉注射，隨後每月進行維持治療。
也可選擇相同劑量每兩個月一次的方案。現實世界數據證實，卡博特韋和利匹韋林的療效並不遜於口服抗愛滋病毒療法。
這種治療方案有利於不願透露HIV感染狀況或儲存和給藥選擇有限的患者。
卡博特韋和利匹韋林也可用作PrEP，儘管利那卡韋 (lenacapavir) 已成為這些藥物的更好替代品。
HIV PrEP的引進標誌著預防新發生HIV感染的重大進展。多年來，人們普遍認為，應該向感染風險較高的人提供HIV PrEP。
利那卡韋 (lenacapavir) 是一種長效注射藥物，自2024年起上市，並於2025年7月在美國和歐盟首次獲得批准。作為首個核准的衣殼抑制劑，它只需每6個月皮下注射一次，並在3期PURPOSE 1和PURPOSE 2試驗中顯示出接近100%的療效。
利那卡韋已被批准用於治療HIV感染，並顯示出令人信服的療效。PrEP 試驗結果令人鼓舞，《科學》雜誌將其評為 2024 年度科學突破。
其他長效 PrEP 方案正在開發中，包括口服核苷反轉錄酶易位抑制劑 ( nucleoside reverse transcriptase translocation inhibitor, NRTTI ) MK-8527，該藥物計畫每月給藥一次，後期可每 6 個月給藥一次，適合不想注射的患者。
MK-8527 與第一個 NRTTI 藥物 islatravir 相似，後者在數名受試者出現 CD4 細胞數減少後於 3 期臨床試驗中停止。 MK-8527 在 2 期臨床試驗中未顯示這些影響，預計對依從性較低的患者有效。
治癒性策略
如果沒有持續的依從性，HIV 病毒量可能會在幾天內反彈，使患者及其伴侶面臨 HIV 傳播風險。治癒性療法是預防愛滋病相關疾病和新發感染之最有效方法。
最近的進展使 HIV 研究史上首次實現治癒成為可能。
廣譜中和HIV抗體（Broadly neutralizing HIV antibodies, bNAb）可針對HIV包膜中高度穩定的區域，並有望成為治療和治癒策略。
它們的應用目前仍僅限於臨床試驗，而bNAb在這些試驗中已顯示出良好的效果。在這些研究中，受試者停止抗病毒療法（ART），並接受bNAb與注射用抗病毒藥物合併使用，以達到長期或永久性的病毒抑制。
然而，挑戰依然存在：bNAb必須產生持續的免疫反應，而這尚未實現。
在一些受試者中，bNAb重塑了病毒儲藏庫，並增強了人體的免疫反應，從而支持了長期感染的控制。需要進一步研究以確定影響bNAb療效及其潛在治療用途的個別因素。
長期以來，HIV研究一直致力於開發預防性和治療性疫苗，其主要目標是透過靶向病毒包膜的保守區域，誘導能夠中和各種HIV株的bNAb。
目前已測試了多種疫苗方法，包括使用無害病毒遞送 HIV 抗原並刺激免疫反應的病毒載體、使用純化 HIV 蛋白觸發免疫的蛋白質疫苗，以及指導細胞產生 HIV 抗原並引發免疫反應的信使 RNA (mRNA) 疫苗。
由於 COVID 疫苗研究，HIV mRNA 疫苗的研發速度加快。儘管 mRNA 技術最初是為 HIV 研發的，但在 COVID 大流行期間得到了廣泛應用。
從這項經驗中獲得的啟發，目前正被用於改進 HIV mRNA 疫苗，以產生比早期實驗候選疫苗更強的免疫反應。
新的 HIV 治療策略和潛在的治癒方法通常結合多種方法。 「休克並殺死」( shock and kill )方法使用潛伏逆轉劑和 bNAb 來活化和消除潛伏的 HIV 病毒儲庫，而「阻斷並鎖定」( block and lock )方法使用潛伏促進劑來維持病毒的休眠。
諸如 CRISPR-Cas9 之類的基因組編輯技術也可能有助於清除體內的 HIV 病毒儲庫。正在進行的臨床試驗將確定哪些組合對長期病毒抑制和潛在治癒最有效。
資金至關重要
四十年來，愛滋病毒研究仰賴強而有力的政治承諾和資金，但這些資金目前正在減少。曾經的主要資助者美國已撤回其支持，德國、法國、荷蘭和英國也已縮減了資助。如果沒有協調一致的國際資金，開發愛滋病毒治癒療法的前所未有的機會可能會喪失。
引用：愛滋病毒很快就會被治癒嗎？新療法帶來希望 – Medscape – 2025年10月15日
Will HIV Soon Be Curable? New Therapies Offer Hope
Barbara Zenz / October 15, 2025 / Medscape Medical News
In 1981, physicians in Los Angeles reported five young patients with Pneumocystis pneumonia, a rare lung infection later recognized as the first sign of HIV infection and a defining illness of AIDS.
At that time, the clinicians were puzzled. Opportunistic infections typically occur only in individuals with severe immune suppression; however, the cause, HIV, remains unknown.
The disease soon spread globally and became a pandemic until the introduction of zidovudine (azidothymidine), the first effective antiretroviral drug, in 1987.
After more than 40 years of research, HIV infection is viewed as a manageable rather than fatal chronic condition. With combination antiretroviral therapy (ART), individuals with HIV can live normal lives and do not transmit the virus sexually when their viral load is undetectable.
Despite these advances and decades of intensive research, the disease remains untreatable. With a few exceptions, all efforts to permanently eliminate the virus from the body have been unsuccessful.
This is largely because HIV-1 and the much rarer HIV-2 are highly genetically variable and largely evade the human immune system. Therefore, achieving sustained remission or a cure through viral elimination requires diverse strategies, persistence, and a substantial trial-and-error approach.
Researchers from France reminded the medical community that a cure for HIV is possible in an article published in The Lancet HIV. The article called for building on past successes and prioritizing curative therapies amid global cuts in HIV treatment.
Despite effective therapies and preventive strategies, 630,000 individuals died worldwide from AIDS-related illnesses, 40.8 million live with HIV, and 1.3 million were newly infected. According to the authors, these figures underscore the urgent need for curative therapies. Without sufficient funding, previous progress could be lost by 2030, and the pandemic cannot end without a cure.
The French Nobel laureate Françoise Barré-Sinoussi, a co-author of the article, began researching retroviruses in the early 1970s at the Pasteur Institute in Paris and later led its “Regulation of Retroviral Infections” department.
She led the 1983 paper that first identified HIV as the cause of AIDS, which is now freely accessible, thanks to co-author Willy Rozenbaum. Barré-Sinoussi and Luc Montagnier received the 2008 Nobel Prize in Physiology and Medicine for discovering the virus.
HIV therapy has several turning points that have significantly improved the quality of patient care. Key milestones include the development of ART, the introduction of HIV pre-exposure prophylaxis (PrEP), and the availability of multidrug therapies as single-tablet regimens. In recent years, injectable and long-acting therapies have expanded treatment and prevention options.
PrEP Breakthrough
Despite all this progress, HIV infection remains a global health concern. Low-threshold access to ART and PrEP is far from universal, yet it is essential to significantly reduce new infections, the incidence of AIDS-related illnesses, and AIDS-related deaths in the coming years.
Stigma and discrimination continue to cause social withdrawal and treatment avoidance, especially in the most affected countries.
Poor adherence also increases the risk for resistance to common HIV medications, such as dolutegravir, particularly where resistance testing is limited because of cost.
Long-acting HIV therapies have been developed to overcome these challenges. Since 2020, cabotegravir, the first injectable HIV integrase inhibitor, has been an alternative to daily oral ART.
After a 28-day oral induction phase to identify intolerances, patients received a single initiation dose of 600 mg cabotegravir and 900 mg rilpivirine intramuscularly, followed by monthly maintenance therapy.
A bimonthly regimen at the same dose is also available. Real-world data have confirmed that cabotegravir and rilpivirine are not inferior to oral ART in terms of efficacy.
This treatment benefits patients who do not want to disclose their HIV infection status or have limited storage and administration options.
Cabotegravir and rilpivirine can also be used as PrEP, although lenacapavir has emerged as a better alternative to these agents.
The introduction of HIV PrEP has marked a significant advance in the prevention of new HIV infections. For several years, there has been a broad consensus that HIV PrEP should be offered to individuals at substantial risk for infection.
Lenacapavir, a long-acting injectable drug, has been available since 2024 and was initially approved in the US and EU in July 2025. As the first approved capsid inhibitor, it requires subcutaneous administration only every 6 months and has demonstrated nearly 100% efficacy in the phase 3 PURPOSE 1 and PURPOSE 2 trials.
Already approved for treating HIV infections, lenacapavir has shown compelling results in PrEP trials, and Science named it the 2024 Scientific Breakthrough of the Year.
Other long-acting PrEP options are in development, including the oral nucleoside reverse transcriptase translocation inhibitor (NRTTI) MK-8527, intended for monthly dosing or, in later phases, every 6 months, making it suitable for patients who prefer to avoid injection.
MK-8527 is similar to the first NRTTI, islatravir, which was stopped in phase 3 after several participants experienced CD4 cell count reductions. MK-8527 did not show these effects in phase 2 trials and is expected to benefit patients with low adherence.
Curative Strategies
Without consistent adherence, the HIV viral load can rebound within days, putting patients and their partners at risk for HIV transmission. Curative therapy is the most effective method for preventing AIDS-defining illnesses and new infections.
Recent advances have made a cure possible for the first time in the history of HIV research.
Broadly neutralizing HIV antibodies (bNAbs) target highly stable regions of the HIV envelope and show promise as therapeutic and curative strategies.
Their use is still limited to clinical trials, and bNAbs have shown promising results in these trials. In these studies, participants stopped ART and received bNAbs with injectable antivirals to achieve long-term or permanent viral suppression.
However, challenges remain: bNAbs must generate a sustained immune response, which has not yet been achieved.
In some participants, bNAbs reshaped viral reservoirs and strengthened the body’s immune response, supporting long-term infection control. Further research is needed to determine the individual factors that influence the efficacy of bNAbs and their potential therapeutic use.
HIV research has long focused on developing preventive and therapeutic vaccines, with the main goal of inducing bNAbs that can neutralize diverse HIV strains by targeting the conserved regions of the viral envelope.
Several vaccine approaches have been tested, including viral vectors that use harmless viruses to deliver HIV antigens and stimulate an immune response, protein-based vaccines that use purified HIV proteins to trigger immunity, and messenger RNA (mRNA) vaccines that instruct cells to produce HIV antigens and generate an immune response.
The development of HIV mRNA vaccines has accelerated due to COVID vaccine research. Although mRNA technology was originally explored for HIV, it was widely used during the COVID pandemic.
Insights from this experience are now being used to improve HIV mRNA vaccines and produce stronger immune responses than those of earlier experimental candidates.
New strategies for HIV treatment and potential cures often combine multiple approaches. The “shock and kill” method uses latency-reversing agents with bNAbs to activate and eliminate latent HIV reservoirs, while the “block and lock” approach uses latency-promoting agents to maintain viral dormancy.
Genome editing techniques, such as CRISPR-Cas9, may also help remove HIV reservoirs from the body. Ongoing clinical trials will determine which combinations are the most effective for long-term viral suppression and potential cure.
Funding Matters
Four decades of HIV research have relied on strong political commitment and funding, which are now declining. The USA, once the main funder, has withdrawn its support, and Germany, France, the Netherlands, and the UK have scaled back. Without coordinated international funding, the unprecedented opportunity to develop curative therapies for HIV could be lost.
Cite this: Will HIV Soon Be Curable? New Therapies Offer Hope – Medscape – October 15, 2025.
