正值全球醫療衛生經費削減之際FDA 批准利那卡帕韋(lenacapavir) 可能阻礙其推廣
Kai Kupferschmidt / 2025年6月18日 / 健康 / ScienceInsider
吉利德科學公司已將其抗病毒治療藥物利那卡帕韋重新製成預防愛滋病毒感染的藥物。 Nardus Engelbrecht/AP
愛滋病領域經歷了起起伏伏，但很少有藥物能像利那卡帕韋一樣給人帶來如此大的希望。注射一次抗病毒藥物就可以在整整 6 個月的時間裡預防愛滋病毒感染——這種類似疫苗的保護盾可能會重振全球對抗愛滋病毒流行的進程。今天，美國食品藥物管理局批准該藥物作為愛滋病預防藥物。但伴隨著希望的同時也帶來了擔憂，即利那卡帕韋可能無法惠及所有可能從中受益的人。
FDA 的決定將為全球推廣開闢道路。奧斯瓦爾多·克魯茲基金會的愛滋病毒研究員 Beatriz Grinsztejn 表示：「現在其他國家開始行動起來，因為其他國家的批准都取決於這次首次批准」。她是全球兩項試驗之一的首席研究員，在這兩項試驗中，lenacapavir 預防了超過 4,000 多人幾乎所有的愛滋病毒感染。
然而，在唐納德·川普總統的政府取消了大多數美國對外援助計畫、削減了數十億美元用於愛滋病治療和預防的資金之際，被《科學》雜誌評為 2024 年度突破的利那卡韋卻應運而生。美國其 2026 年預算提案將把總統愛滋病緊急救援計畫 (PEPFAR) 的資金減少三分之一。格林斯坦表示：「我們都曾期望，總統防治愛滋病緊急救援計畫將成為推動利那卡帕韋『全球』推廣的主要動力」。現在，她說：「其他參與者需要發揮主導作用」。
吉利德科學公司開發了利那卡帕韋，並將其以Yeztugo的名義上市。該公司執行長發表聲明稱：「這是數十年來在對抗愛滋病毒鬥爭中歷史性的一天。Yeztugo是我們這個時代最重要的科學突破之一，為終結愛滋病毒流行提供了一個真正的機會」。米切爾·沃倫 (Mitchell Warren) 是致力於愛滋病預防宣傳的非營利組織 AVAC 的負責人，他認為，利那卡帕韋為對抗愛滋病的絕佳機會。儘管新增感染人數自 1995 年 330 萬的高峰以來，已大幅下降，但全球每年新增感染人數仍停留在 130 萬人左右。
被稱為暴露前預防（PrEP）的愛滋病毒預防策略，即是將通常用於治療感染的藥物給予未感染者，但這種策略尚未實現其前景。儘管全球 PrEP 的採用率每年增加約 20%，但在許多愛滋病毒負擔較重的低收入地區，它仍然不受歡迎。總體而言，全球每天服用 PrEP 藥物的人數估計為 300 萬人，遠低於聯合國設定的 2,100 萬人的目標。
問題的主要部分在於，對許多人來說，每天服用藥片很困難。這就是吉利德公司研發的一年兩次的利那卡帕韋注射劑如此有前景的原因之一。另一個原因是，它屬於一類針對愛滋病毒衣殼（愛滋病毒基因周圍的蛋白質外殼）的新型藥物。衣殼抑制劑尚未廣泛用於治療愛滋病毒，因此如果某些病毒株對利那卡帕韋產生抗藥性，則不會廣泛阻礙治療計劃。
沃倫說：「這是我們應對這場44 年來之流行病最具變革性的預防產品」。但他補充說，現有的長效 形式之PrEP提供了一個警示故事。一種名為卡博特韋 (cabotegravir) 針劑化合物可提供 2 個月的保護，但全球僅有 15,000 人接受注射。卡博特韋於 2021 年推出，最初每年的花費約為 240 美元，對於許多國家來說太昂貴。低需求反過來又導致產量低下，喪失了經濟規模。沃倫說，利那卡帕韋有機會取得更好的效果。 「這一次，我們必須有遠大的目標，專注於產生影響，簡化交付，讓 PrEP 廣為人知，並且不要害怕創造需求」。
有跡象顯示這種情況正在發生。吉利德公司也銷售每日服用的 PrEP 藥片，並因其定價而受到批評，該公司已向全球六家仿製藥製造商授予免版稅生產該藥物的許可。這些公司將被允許向 120 個低收入國家銷售該藥物。吉利德的 Jared Baeten 表示，技術轉移已在去年年底完成。他說：「他們現在擁有的資訊不僅能夠合成活性藥物成分，還能合成無菌成品」。
在仿製藥問世之前，吉利德將向低收入國家免費提供該藥物。然而，中等收入國家，如巴西和秘魯，愛滋病疫情嚴重，且是大規模利那卡韋試驗的地點，將無法獲得仿製藥。 「希望我們能以可負擔的價格獲得這種藥物」，Grinsztejn 說道。
2024 年 12 月，為對抗愛滋病、瘧疾和結核病計畫提供資金的夥伴關係組織全球基金宣布，將與美國總統防治愛滋病緊急救援計畫 (PEPFAR) 合作，計畫在 3 年內為低收入和中低收入國家的 200 萬人開始使用利那卡帕韋。這項活動得到了兒童投資基金會和蓋茲基金會的支持。
擬議削減總統防治愛滋病緊急救援計畫將威脅到這些計畫但可能不會使其脫軌。川普的預算提案特別提到引入「每年兩次的愛滋病預防注射」，這與白宮早先暗示 PEPFAR 將不再支持 PrEP 的措辭形成鮮明對比。總統防治愛滋病緊急救援計畫前幕僚長吉拉爾·拉特沃西安 (Jirair Ratevosian) 表示：「這是一個強烈的信號，顯示他們對此很感興趣」。「我認為這是一個巨大的機遇，我們需要駕駛卡車來突破這個機遇」。
由於川普希望減少捐款，全球基金面臨來自其最大捐助國美國的資金不確定性。但該基金供應業務主管楊輝表示，讓 200 萬人獲得利那卡韋的承諾不會改變。她補充道，儘早擴大獲取管道非常重要，因為這將向仿製藥製造商顯示市場和需求的存在。
楊說，全球基金可能會重點關注少數已經實施 PrEP 計畫並在長效注射劑方面有一定經驗的國家。沃倫說，集中精力於此可以幫助捐助者和政府了解利那卡帕韋可能產生的影響。「我們必須證明利那卡帕韋確實可以改變新感染的曲線，我相信它可以」。
即使像美國這樣的高收入國家也能從這種藥物中受益。在本月發表的一篇論文中，美國疾病管制與預防中心的科學家估計，美國有 225 萬人應該優先接受 PrEP 治療。事實上，大約只有五十萬人正在服用該藥物。
格林斯坦表示，目標應是覆蓋那些從未使用過 PrEP 的人。她說：「但我擔心的是，這種療法仍主要適用於那些已經口服 PrEP且 效果良好的人」。南非愛滋病研究中心負責人薩利姆·阿卜杜勒·卡里姆說道，要改變這種狀況，需要創新思維和大量關於如何最好地實施半年注射藥物的研究。他說：「這是一種需要開發的全新方法」。「如果我們只是將利那帕韋放入診所和藥店，那它就只會被放在貨架上」。
吉利德目前正在尋求歐洲和其他地區的批准。世界衛生組織 (WHO) 全球愛滋病毒、肝炎和性傳播感染計畫主任梅格·多爾蒂 (Meg Doherty) 表示，該組織將於 7 月 14 日在盧安達基加利舉行的國際愛滋病毒會議上發布使用 lenacapavir 作為 PrEP 的新指南。 「這些指導方針將為各國提供重要建議，幫助它們將這一科學突破最好地帶給最需要它的社區」。她說，歐洲藥品管理局對利那卡帕韋做出決定後，世界衛生組織將很快對該藥物進行「預審」。 「透過整合指導方針和資格預審——兩個通常獨立但至關重要的過程——我們確保當首批利那卡帕韋到達中低收入國家時，世衛組織的監管許可和臨床指導都已準備就緒」。
利那卡帕韋的良好開端也可能為更好的 PrEP 形式奠定基礎。吉利德已經重新配製了其藥物，將更多的分子裝入更小的體積中。三月所公佈的臨床試驗數據顯示該藥物在血液中的含量足夠高，可以在一整年內預防愛滋病毒感染。
該配方的更大規模的第三階段試驗可能會在今年稍後開始。而默克公司一直則在研發每月服用一次的 PrEP 藥丸，針對的是病毒酶而不是衣殼，該藥丸也可能在 2028 年上市。
華倫表示，利那卡帕韋仍有風險可能再次成為被浪費掉的機會。 「但我們也可能有機會透過利那卡帕韋實現一半的目標，到 2028 年，我們所建立的平台可將利那卡帕韋的服用時間改為每年一次，而口服藥片則改為每月一次，這樣我們就能開始看到發生率的下降」，他說。他說，這是全世界都要做出的決定。 doi: 10.1126/science.zoeegav
作者：凱·庫普弗施密特
凱·庫普弗施密特（Kai Kupferschmidt）是《科學》雜誌駐德國柏林的特約記者。他長期報道傳染病和全球健康問題，但他也撰寫有關迷幻藥和科學錯誤訊息的研究。他的作品出現在許多德國媒體上，並獲得多個獎項，包括德國愛滋病基金會新聞獎和美國國家社會工作者協會社會科學新聞獎。他是播客“Pandemia”的共同創作者和聯合主持人。 Kai 擁有分子生物醫學學位，並撰寫了一本有關藍色科學的書：《藍色》，尋找大自然最稀有的顏色。他在 Bluesky 上的網址是 @kakape.bsky.social。
Will long-lasting HIV preventive be a game changer—or a missed opportunity?
FDA’s approval of lenacapavir comes at a time when global health cuts could stall its rollout
Kai Kupferschmidt / 18 Jun 2025 / Health / ScienceInsider
Gilead Sciences has repurposed its antiviral treatment lenacapavir into a shot that prevents HIV infections. Nardus Engelbrecht/AP
The HIV field has seen its share of ups and downs, but rarely has something arrived with as much hope as lenacapavir. A single shot of the antiviral can protect against HIV infection for a full 6 months—a vaccinelike shield that might revive progress against the global epidemic of the AIDS virus. Today, the U.S. Food and Drug Administration approved the drug as an HIV preventive. But along with hope, the moment brings fears lenacapavir may not reach all the people who could benefit most from it.
FDA’s decision will open the way to a global rollout. “The ball is starting to roll for the other countries now, because other approvals depend on this first approval,” says Beatriz Grinsztejn, an HIV researcher at the Oswaldo Cruz Foundation and principal investigator on one of two global trials in which lenacapavir prevented nearly all HIV infections in more than 4000 people.
But lenacapavir, which was Science’s 2024 Breakthrough of the Year, arrives as President Donald Trump’s administration has axed most U.S. foreign aid programs, cutting billions of dollars for HIV treatment and prevention. Its budget proposal for 2026 would reduce funding of the President’s Emergency Plan for AIDS Relief (PEPFAR) by one-third. “We all had this expectation that PEPFAR would be the major driver for [global] rollout of lenacapavir,” Grinsztejn says. Now, she says, “Other actors need to take the lead.”
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Gilead Sciences, which developed lenacapavir and will market it as Yeztugo, released a statement from its CEO saying in part, “This is a historic day in the decades-long fight against HIV. Yeztugo is one of the most important scientific breakthroughs of our time and offers a very real opportunity to help end the HIV epidemic.” Mitchell Warren, who heads AVAC, a nonprofit that focuses on HIV prevention advocacy, agrees lenacapavir presents a “remarkable opportunity” to make new headway against the epidemic. Although new infections have dropped dramatically since the 1995 peak of 3.3 million, progress has stalled at about 1.3 million new infections around the globe each year.
HIV prevention strategies known as preexposure prophylaxis (PrEP), in which drugs normally used to treat infections are given to uninfected people, have not realized their promise yet. Although PrEP uptake has been increasing by about 20% every year globally, it is still not popular in many lower income regions with a high burden of HIV. Overall, an estimated 3 million people worldwide take a daily PrEP pill, far short of a goal of 21 million set by the United Nations.
A major part of the problem has been that taking a daily pill has proved difficult for many people. That is one reason the twice-a-year shot of lenacapavir, developed by Gilead, holds so much promise. Another reason is that it belongs to a new class of drugs that target the HIV capsid, the protein shell around its genes. Capsid inhibitors are not yet widely used to treat HIV, so if some strains developed lenacapavir resistance, it would not broadly hamper treatment programs.
“This is the most transformative prevention product we’ve had in 44 years of this epidemic,” Warren says. But he adds that an existing long-lasting form of PrEP offers a cautionary tale. A shot of a compound called cabotegravir offers 2 months of protection, but just 15,000 people around the world get it. Introduced in 2021, cabotegravir initially cost about $240 per year, far too expensive for many countries. Low demand in turn kept production low, forfeiting economies of scale. There is a chance to do better with lenacapavir, Warren says. “This time we have to think big, focus on delivering impact, simplify delivery, make PrEP famous, and not be afraid to create demand.”
There are some signs that this is happening. Gilead, which also markets daily PrEP pills and has been criticized for their pricing, has already granted licenses to produce the drug, royalty-free, to six generic manufacturers around the world. These firms will be allowed to sell the drug to 120 lower income countries. The tech transfer was finished late last year, says Gilead’s Jared Baeten. “They have the information now to be able to both synthesize the active pharmaceutical ingredient as well as everything through to a sterile finished product,” he says.
Until generics arrive, Gilead will provide the drug at no profit in low-income countries. Middle-income countries such as Brazil or Peru, which have large HIV epidemics and were sites in the big lenacapavir trials, will not have access to generics, however. “Hopefully there will be a way for us to have access to this drug at an affordable price,” Grinsztejn says.
In December 2024, the Global Fund, a partnership that finances programs to fight AIDS, malaria, and tuberculosis, announced that together with PEPFAR it would aim to start 2 million people in low- and lower middle–income countries on lenacapavir within 3 years. The effort is supported by the Children’s Investment Fund Foundation and the Gates Foundation.
The proposed cut to PEPFAR threatens those plans but may not derail them. Trump’s budget proposal specifically mentions the introduction of “a twice-a-year HIV prevention injection,” a contrast to earlier White House language suggesting PEPFAR would no longer support PrEP. “That is a really strong signal that they are interested in this,” says Jirair Ratevosian, a former chief of staff at PEPFAR. “I think that is a huge window of opportunity that we need to drive a truck through basically.”
The Global Fund faces uncertainty about money from the United States, its No.1 donor, as Trump looks to reduce contributions. But its commitment to getting 2 million people on lenacapavir stands, says Hui Yang, the fund’s head of supply operations. Expanding access early, she adds, is important because it will show generic manufacturers there is a market and a demand.
The Global Fund will likely focus on a small number of countries that already have a PrEP program and have some experience with long-acting injectables, Yang says. Concentrating on them could help show donors and governments the impact lenacapavir can have, Warren says. “We have to prove that lenacapavir can actually bend the curve of new infections, and I believe it can.”
Even higher income countries such as the U.S. could benefit from the drug. In a paper published this month, scientists from the Centers for Disease Control and Prevention estimate that 2.25 million people in the U.S. should be prioritized for PrEP. In reality, about half a million people are taking it.
The goal has to be reaching people who have never used PrEP before, Grinsztejn says. “The fear I have is that this becomes mostly available for those who are already doing well on oral PrEP,” she says. Changing that will take innovative thinking and a lot of studies on how best to implement a half-a-year shot, says Salim Abdool Karim, who runs the Centre for the AIDS Programme of Research in South Africa. “This is a completely new approach that has to be developed,” he says. “If we simply take lenacapavir and put it into the clinics and put it into the pharmacies, it will sit on the shelves.”
Gilead is now pursuing approvals in Europe and elsewhere. Meg Doherty, director of the Global HIV, Hepatitis and STIs Programmes at the World Health Organization (WHO), said the group would launch new guidelines on using lenacapavir as PrEP on 14 July at an international HIV conference in Kigali, Rwanda. “These guidelines will provide critical recommendations for countries on how best to bring this scientific breakthrough to the communities that need it the most.” WHO “prequalification” of the drug would follow soon after the European Medicines Agency’s decision on lenacapavir, she said. “By bringing together guidelines and prequalification—two often separate but critical processes—we are ensuring that when the first doses of lenacapavir reach low- and middle-income countries, both the WHO regulatory clearance and the clinical guidance are ready.”
A strong start for lenacapavir might also lay the groundwork for even better forms of PrEP. Gilead has already reformulated its drug, fitting more of the molecule into a smaller volume. Clinical trial data presented in March suggest the drug stays at high enough levels in the blood to protect against HIV infection for a full year.
A bigger, phase 3 trial of that formulation could start later this year. And Merck has been working on a monthly PrEP pill, targeting viral enzymes rather than the capsid, that could also be available by 2028.
There’s still a risk that lenacapavir becomes another squandered opportunity, Warren says. “But there’s also a possibility that we get this half right with lenacapavir, and we build the platform to move to once-a-year lenacapavir and a monthly oral tablet by 2028 and we begin to see a decline in incidence,” he says. It’s a decision, he says, for the world to make.
doi: 10.1126/science.zoeegav
About the author
Kai Kupferschmidt
Kai Kupferschmidt is a contributing correspondent for Science magazine based in Berlin, Germany. He has long covered infectious diseases and global health, but he also writes about research into psychedelics and the science of misinformation. His writing has appeared in many German outlets, and he has won several awards, including the Journalism Award of the German Aids Foundation and an NASW Science in Society Journalism Award. He is co-creator and co-host of the podcast “Pandemia.” Kai has a degree in molecular biomedicine and has written a book on the science surrounding the color blue: Blue. In Search of Nature’s Rarest Color. He is on Bluesky at @kakape.bsky.social.
