www.thelancet.com/hiv Vol 11 September 2024
第 25 屆國際愛滋病大會於 7 月 22 日至 26 日在德國慕尼黑舉行，主要議題是：每 6 個月注射一次來那卡韋 (lenacapavir) 預防愛滋病毒的 PURPOSE 1 試驗的結果。暴露前預防（PrEP）的新方法取得了顯著的效果。與預期的背景 HIV 發病率相比，以及與每日口服替諾福韋藥物 (tenofovir-based drugs) 預防相比，每 6 個月服用一次的來那卡韋 (lenacapavir) 預防 HIV 的效果為 100%。 2,134 名參與者中完全沒有感染。同樣引人注目的是這項研究本身，該研究是在南非和烏干達的少女和年輕女性群體中進行的。另一項試驗「PURPOSE 2」正在男男性行為人群中進行，該試驗需要獲得確認結果才能獲得吉利德產品的使用許可，但從各方面來看，這只是一個形式，預計將於今年晚些時候進行。每年兩次注射預防愛滋病毒可能會成為遊戲規則改變者──在《刺胳針愛滋病毒》雜誌上我們不會輕易提及這句話。
來那卡韋 (Lenacapavir) 注射 PrEP 的開發計畫因在撒哈拉以南非洲地區少女和年輕女性中完成首次監管試驗而受到讚揚。該族群仍然是愛滋病毒負擔最重的族群，發生率也很高。從歷史上看，由於在可能懷孕的人身上進行試驗存在困難，青春期女孩和年輕女性在藥物開發方面一直得不到充分服務。但這種排除造成了一個悖論：最需要愛滋病毒創新的人群被排除在外，而預防或治療妊娠期愛滋病毒的新藥的效果只能在後來的人群監測中才能發現。多年來，許多人都強調了這個缺陷，我們體認到社群團體和研究人員他們在推動製藥公司將這一人群納入試驗的運作。吉利德在人群中進行的大規模監管試驗值得讚揚，所有參加試驗的女性現在都可以繼續她們選擇的預防方法。
聯合國愛滋病規劃署最近發布的報告《當前的緊迫性：愛滋病正處於十字路口》中的數據清楚地顯示了預防創新的必要性。據估計，在 3,990 萬愛滋病毒感染者中，近四分之一沒有接受治療。接受口服 PrEP 的總人數從 2017 年的 20 萬人增加到 2023 年的約 350 萬人，但這仍然遠低於 在2025 年要有 95% 的愛滋病毒高危險群獲得 PrEP 的目標，即 2,100萬人使用PrEP。重點族群和年輕女性在獲得口服 PrEP 方面的服務尤其不足，許多人難以堅持每日口服或採事件驅動的治療方案。治療獲取方面的差距和 PrEP 提供的失敗意味著愛滋病毒發病率仍然遠高於全球目標：2023 年估計將有 130 萬人新感染愛滋病毒，而 2025 年的目標是 37 萬人。
為期 6 個月的注射預防方案，例如來那卡韋 (Lenacapavir) 提供的方案，可以解決某些人群在使用口服 PrEP 時遇到的許多困難。對於生活不穩定的人、孕婦和哺乳期婦女以及權力失衡的人來說，它可能特別有價值。越來越多的預防選擇環境值得歡迎：從醫療的男性包皮環切術和保險套，到以治療作為預防，以及對U=U（無法檢測到等於不會傳播）、殺菌陰道環、口服PrEP 和注射PrEP 的日益了解，將使得人們能夠破壞傳輸。人們在一生中可能會利用不同的方法來適應不斷變化的環境。對PURPOSE 1 的觀察影顯示，來那卡韋 (Lenacapavir) 將成為年輕女性的重要選擇。正如聯合國愛滋病規劃署的報告所述：「如果潛在使用者能夠快速且經濟地獲得這種 PrEP 方案，則可能預示著愛滋病毒預防方面的突破」。
這句話的關鍵字是「快速且經濟實惠」。吉利德透過在最有需要的人群中進行監管試驗，取得了良好的開端。該公司已經在為低收入和中等收入國家的製藥公司申請直接許可證，以生產用於預防的注射型萊那卡韋 (Lenacapavir)；儘管他們並不尋求透過藥品專利池組織獲得許可，但這項決定引起了一些人的質疑。來那卡韋 (Lenacapavir) 已被用作少數治療經驗豐富患者的治療方法，儘管每年 40,000 美元的價格意味著大多數人無法承受。為了廣泛使用 PrEP，價格需要低很多。全世界都在關注吉利德在未來幾個月的表現。 ■ 刺胳針愛滋病毒
A game-changer for PrEP if access is adequate
www.thelancet.com/hiv Vol 11 September 2024
The 25th International AIDS Conference, held July 22–26 in Munich, Germany, was dominated by one topic: the results of the PURPOSE 1 trial of lenacapavir 6-monthly injections for the prevention of HIV. The novel approach to pre-exposure prophylaxis (PrEP) had remarkable results. Compared with the expected background HIV incidence, and in comparison to daily oral prevention with tenofovir-based drugs, lenacapavir given every 6 months was 100% effective in preventing HIV. There were no infections at all in 2134 participants. Equally remarkable was the study itself, which was done in a population of adolescent girls and young women in South Africa and Uganda. Confirmatory results from another trial, PURPOSE 2, which is ongoing in populations of men who have sex with men, are required for Gilead’s product to be licensed for use, but by all accounts this is a mere formality, expected later this year. A twice-yearly injection to prevent HIV could be a game changer—a phrase that we do not throw around lightly in The Lancet HIV.
The development programme for lenacapavir as injectable PrEP is to be applauded for completing the f irst regulatory trial in adolescent girls and young women in sub-Saharan Africa. This population still bears the greatest burden of HIV and experiences high incidence. Historically, adolescent girls and young women have been underserved in drug development because of perceived difficulties in doing trials involving people who might become pregnant. But this exclusion has created a paradox: the population most in need of innovations in HIV has been excluded from them, and the effects of new drugs to prevent or treat HIV in pregnancy are only discovered later in population-level surveillance. Over the years, many have highlighted this shortcoming, and we acknowledge the campaigning of community groups and researchers who have pushed for pharmaceutical companies to include this population in trials. Gilead is to be commended for doing a large regulatory trial in the population. All women enrolled in the trial will now be able to continue the prevention approach of their choice.
The need for innovation in prevention is evident in the figures contained in the recently published UNAIDS report The Urgency of Now: AIDS at a Crossroads. Of 39·9 million people estimated to be living with HIV almost a quarter are not receiving treatment. The total number of people on oral PrEP rose from 200 000 in 2017 to about 3·5 million in 2023, but this remains far short of the 2025 target of 95% of people at risk of HIV with access to PrEP, which would see 21·1 million people using PrEP. Key populations and young women are particularly underserved by access to oral PrEP, and many have difficulty in adhering to oral daily or event driven regimens. Gaps in treatment access and failures in PrEP delivery mean that HIV incidence remains far above global targets: in 2023 an estimated 1·3 million people newly acquired HIV compared with the 2025 target of 370 000.
A 6-monthly injectable prevention option, such as that provided by lenacapavir, could address many of the difficulties that some populations have in using oral PrEP. It could be particularly valuable for people with instability in their lives, pregnant and breastfeeding women, and people in relationships with power imbalances. A growing milieu of prevention options is to be welcomed: from medical male circumcision and condoms, to treatment as prevention and the growing understanding of U=U (undetectable equals untransmittable), microbicidal vaginal rings, oral PrEP, and injectable PrEP will empower people to disrupt transmission. People throughout their lives might avail themselves of different methods as suit their changing circumstances. Observations of PURPOSE 1 suggest that lenacapavir will be an important option for young women. As the UNAIDS report says: “If this PrEP option is made available rapidly and affordably to potential users, it could herald a breakthrough for HIV prevention.”
The key phrase in this quote is “rapidly and affordably”. Gilead has got off to a great start by doing regulatory trials in populations with the greatest need. The company is already in the process of working out direct licences for drug companies in low-income and middle-income countries to produce injectable lenacapavir for prevention; although they are not pursuing licensing through the medicines patent pool, a decision that has raised some eyebrows. Lenacapavir is already in use as a treatment for a small number of highly treatment-experienced patients, although the price of US$40 000 per year means that for most it is unaffordable. For widespread PrEP use, the price will need to be a lot lower. The world is watching to see how Gilead acts in the coming months. ■ The Lancet HIV