活動人士說，愛滋預防工具到達非洲太慢了
一種長效注射藥物在七個非洲國家進行了測試，但他們目前尚不清楚何時可以使用它。
資料來源：By Andrew Green,in Kampala,Uganda / 24 JUNE 2022 / VOL 376 ISSUE 6600 / SCIENCE / 財團法人台灣紅絲帶基金會編譯
莫三比克貝拉的一名性工作者正在接受愛滋病毒檢測。一種可注射的預防性藥物可以為高危人群提供一種預防感染的新方法。
Melb Simiyu 是這裡一家性工作者支持組織的愛滋病毒預防官員，她說她的大多數客戶都問過一種叫做 CAB-L（註1）的藥物甚麼時候可以買到。這種愛滋病毒預防藥物於 2021 年 12 月獲得美國食品和藥物管理局 (FDA) 的批准，可以大大減少與她合作的邊緣群體的感染。
但即使在烏干達和其他六個撒哈拉以南非洲國家的試驗提供了 FDA 批准的關鍵數據，非洲仍然是世界上受愛滋病毒影響最嚴重的地區，但可能要等待很長時間才能以可承受的價格獲得這種藥物。
5 月 27 日，CAB-LA 的開發商 Viiv Healthcare 正式承諾向總部位於日內瓦的 Medicines PatMPP 頒發該藥物的自願許可，這是一種可注射形式的暴露前預防用藥 (PrEP)。如果兩者達成協議，MPP 可以居中仲介與學名藥製造商達成協議，為低收入和中等收入國家生產廉價版本的 CAB-LA。但這些學名藥可能需要數年時間才能上市，活動人士指責 Viiv 拖拖拉拉，該公司否認了這一點。協調非洲社區諮詢委員會的尚比亞 HIV 活動家 Kenly Sikwese 說，在招募該地區的人進行臨床試驗之前，應該就要確保在撒哈拉以南非洲地區的人們能公平獲取。 「Viiv 必須認真對待以便讓每個需要它的人都能使用該產品」，Sikwese 說。
兩種口服版本的 PrEP 已經上市，均作為每日藥丸。它們已被證明可以將包括性工作者和男男性行為者 (MSM) 在內的高危人群中的 HIV 感染減少高達 99%——但只有在持續服用的情況下，許多使用者都覺得很難做到這一點。 CAB-LA 承諾會更有效，因為順從性會更容易。關鍵成分是一種名為cabotegravir 的抗病毒化合物，可防止病毒基因組整合到宿主細胞的DNA 中，被注射到臀部並緩慢釋放到體內。與每日服藥相比，雙月注射意味著使用者更不麻煩且有更多的自由裁量權。
在撒哈拉以南非洲進行的試驗招募了 3,200 名婦女，結果顯示 CAB-LA 在預防新的 HIV 感染方面比口服 PrEP 更有效 89%。在另一項研究中也證明了它的優越性，在四大洲的近 4,600 名 男男性行為者和跨性別女性中。聯合國愛滋病毒/愛滋病聯合規劃署 (UN AIDS) 副執行主任馬修·卡瓦納 (Matthew Kavanagh) 稱 CAB-LA 「可能是十年內出現的最有效的生物醫學預防工具」。
世界衛生組織預計將在 7 月發布 CAB-LA 安全指南，這將促使各國追隨 FDA 的領導並批准它。 Kavanagh 說，聯合國愛滋病規劃署已經與捐助者就其分發籌資問題進行了初步對話，包括美國總統愛滋病緊急救援計畫，該計畫是非洲口服 PrEP 的主要資助者。他說，還有「少數政府表示願意在這方面進行投資」。
但所有人都在等待到底有多少瓶可使用以及其價格是多少。 Viiv 將可注射型 PrEP在美國供應一年定價為 22,000 美元。 Kavanagh 說，對於世界上最貧窮的國家來說，這個數字需要降至目前口服 PrEP 學名藥的價格，即每年不到 100 美元。 「如果比這多得多，我們就沉沒了」，他說。這將使 CABLA 成為「不平等的助推器」。
Viiv 承諾以非營利價格向最貧窮的國家提供 CAB-LA，包括整個撒哈拉以南非洲地區。但該公司不會說這個價格是多少，並且在 3 月份，它發表了一份措辭含糊的聲明，暗示自願許可無助於實現負擔得起的取得目標。此舉令愛滋活動人士感到困惑和憤怒，該聲明已被撤下。 Viiv 的首席醫療官 Harmony Garges 表示，「對我們的承諾存在誤解」，該公司只是「表明這將比過去Viiv已同意提供自願許可生產之口服治療之學名藥更不同、更複雜」。與 MPP 合作的新承諾是「朝著正確方向邁出的一步」，南非預防愛滋病毒和愛滋病宣傳執行主任 Yvette Raphael 說。但是，她補充說，鑑於建立CAB-LA學名藥生產可能需要長達 3 年的時間，「應該在 2020 年停止研究的那一刻就完成」。活動人士還指出，目前尚不清楚有多少低收入和中等收入國家將獲准授權取得學名藥，以及 Viiv 是否會共享技術以幫助製造商提高產量。
Garges 說：「我從激進主義者的角度理解，總是存在一定程度的不耐煩」，但在 CAB-LA 獲得首次監管批准後僅 6 個月，與 MPP 的談判就開始了。「我不認為這是任何延遲的做法」。
降低價格並不是提供藥物的唯一障礙。如果將 cabotegravir 給予已經感染的人，HIV 會產生對 cabotegravir 的耐藥性，並且耐藥性會阻礙其他整合酶抑製劑，包括當前 HIV 治療的支柱 dolutegravir。這就是為什麼美國FDA 要求美國的可注射型 PrEP 接受者首先接受HIV的藥敏檢測。南非開普敦 Desmond Tutu HIV 中心主任 LindaGail Bekker 說，這些都需要花錢，而且執行起來可能很耗時， Bekker 說。如果監管機構確定需要進行此類測試，則官員將不得不考慮要如何提供這些測試。
倡導者熱衷於避免全球推廣口服的 PrEP時所發生的事情，該計畫始於 2015 年，但很快陷入為「太小太慢的示範項目」，愛滋病預防倡導機構 AVAC 的執行董事 Mitchell Warren 說道。到 2020 年，發展中國家接受 PrEP 的人數不足 100 萬人，遠低於聯合國愛滋病規劃署所訂 300 萬人的目標。
AVAC 指出了這次要避免的其他幾個失誤。將口服 PrEP 作為一種專門針對 HIV 高感染風險人群的預防工具的運動，使得一些人因害怕受到污名而猶豫不決。而要求人們到繁忙的診所就診以開始 PrEP 或補充藥物，更加劇了這些恐懼。
烏干達傳染病研究所的高級研究科學家 Andrew Mujugira 牢記這一教訓，希望從烏干達的性工作者、MSM 和跨性別者社區中招募和培訓衛生工作者來提供 CAB-LA。每當藥物到貨時，他都想做好準備，他說：「如果可以買到，如果有人可以支付費用並且可以獲取，那麼這將改變遊戲規則」。
Andrew Green 是駐柏林的記者。
註1. CAB-LA： 或稱長效可注射型 cabotegravir 是由 ViiV Healthcare 開發的一種抗反轉錄病毒藥物，每兩個月給藥一次，作為可注射形式的PrEP。 Cabotegravir 之前在美國和加拿大被批准用於治療，與另一種可注射的抗反轉錄病毒藥物 rilpivirine 聯合使用。2021 年 12 月，CAB-LA 亦被美國額外批准用作預防上之選擇用藥。
HIV prevention tool is too slow to reach Africa, activists say
A long-lasting injectable drug was tested in seven African countries. But it’s unclear when they’ll have access to it
24 JUNE 2022 • VOL 376 ISSUE 6600 / SCIENCE
A sex worker in Beira, Mozambique, gets tested for HIV. An injectable prophylactic drug can give people at high risk a new way to prevent infection.
Melb Simiyu, an HIV prevention officer at a support organization for sex workers here, says most of her clients have asked when a drug called CAB-LA will become available. Approved by the U.S. Food and Drug Administration (FDA) in December 2021, the HIV-prevention drug could drastically reduce infections among marginalized groups like the one she works with.
But even though a trial in Uganda and six other sub-Saharan African countries provided data key for FDA’s approval, Africa, still the part of the world hardest hit by HIV, may face a long wait to get the drug at an affordable price.
On 27 May, CAB-LA’s developer, Viiv Healthcare, made a formal commitment to issue a voluntary license for the drug, an injectable form of pre-exposure prophylaxis (PrEP), to the Geneva-based Medicines PatMPP). If the two reach an agreement, MPP could broker deals with generic manufacturers to produce cheap versions of CAB-LA for low- and middle-income countries. But it may take years before those generics become available, and activists accuse Viiv of dragging its feet, which the company denies. Zambian HIV activist Kenly Sikwese, who coordinates the African Community Advisory Board, says equitable access in sub-Saharan Africa should have been guaranteed before people from the region were recruited for clinical trials. “Viiv’s got to be serious about making the product accessible to everyone who needs it,” Sikwese says.
Two oral versions of PrEP are already available, both as a daily pill. They have been shown to reduce HIV infection in groups at high risk, including sex workers and men who have sex with men (MSM), by up to 99%—but only when taken consistently, which many users find hard. CABLA promises to be more effective because adherence is much easier. The key ingredient, an antiviral compound named cabotegravir that prevents the viral genome from integrating into the DNA of host cells, is injected into the buttock and slowly released into the body. The bimonthly injections mean less hassle and more discretion for the user than a daily pill.
The trial in sub-Saharan Africa, which enrolled 3200 women, showed CAB-LA to be 89% more effective at preventing new HIV infections than oral PrEP. It also proved superior in another study, in nearly 4600 MSM and transgender women across four continents. Matthew Kavanagh, deputy executive director of the Joint United Nations Programme on HIV/AIDS (UNAIDS), calls CAB-LA “potentially the most effective biomedical prevention tool to come along in a decade.”
The World Health Organization is expected to issue safety guidelines for CABLA in July, which should spur countries to follow FDA’s lead and approve it. UNAIDS has had initial conversations about financing its distribution with donors, Kavanagh says, including the U.S. President’s Emergency Plan for AIDS Relief, the major funder of oral PrEP in Africa. There’s also “a handful of governments that say they would like to invest in this,” he says.
But all are waiting to find out how many vials will be available and at what cost. Viiv has priced injectable PrEP at $22,000 for a year’s supply in the United States. For the world’s poorest countries, that figure needs to come down to the current price of generic oral PrEP, less than $100 annually, Kavanagh says. “If it’s a lot more than that, we’re sunk,” he says; that would make CABLA an “inequality booster.”
Viiv has pledged to provide CAB-LA at nonprofit prices to the poorest countries, including all of sub-Saharan Africa. But the company will not say what that price is, and in March, it issued a vaguely worded statement suggesting a voluntary license would not help achieve the goal of affordable access. The move perplexed and enraged activists, and the statement has since been taken down. Harmony Garges, Viiv’s chief medical officer, says there was a “misunderstanding about our commitment” and that the company was only “signposting that this was going to be different, more complex” than manufacturing generic oral treatment, for which Viiv has provided a voluntary license in the past. The new commitment to work with MPP is “a step in the right direction,” says Yvette Raphael, executive director of Advocacy for Prevention of HIV and AIDS in South Africa. But, she adds, “It should have been done the minute the studies were stopped” in 2020, given that setting up generic CABLA production could take up to 3 years. Activists also note that it’s unclear how many low- and middle-income countries will be allowed access to generics under a license and whether Viiv will share technology to help manufacturers ramp up production.
“I appreciate from the activist side that there’s always a level of impatience,” Garges says, but negotiations with MPP started just 6 months after CAB-LA received its first regulatory approval. “I don’t view this as any kind of delayed approach.”
Lowering the price isn’t the only hurdle to providing the drug. HIV can develop resistance to cabotegravir if it is given to a person who is already infected, and the resistance can hamper other integrase inhibitors, including dolutegravir, the backbone of current HIV treatments. That’s why FDA requires injectable PrEP recipients in the United States to first undergo a sensitive HIV test. But those cost money and can be time-consuming to conduct, says LindaGail Bekker, director of the Desmond Tutu HIV Centre in Cape Town, South Africa. If regulators determine such tests are needed, officials will have to consider how to make them available, Bekker says.
Advocates are keen to avoid what happened with the global rollout of oral PrEP, which began in 2015 but was quickly ensnared in “demonstration projects that were too small and too slow,” says Mitchell Warren, executive director of AVAC, an HIV prevention advocacy group. By 2020, fewer than 1 million people in developing countries were on PrEP, far short of the UNAIDS goal of 3 million.
AVAC identified several other missteps to avoid this time. Campaigns that framed oral PrEP as a prevention tool specifically for those at high risk of HIV infection made some people hesitant to ask for it for fear of stigma. Requiring people to visit busy clinics to start PrEP or pick up refills heightened those fears.
Taking that lesson to heart, Andrew Mujugira, a senior research scientist at Uganda’s Infectious Diseases Institute, hopes to recruit and train health workers from within communities of sex workers, MSM, and trans people in Uganda to deliver CAB-LA. Whenever the drug arrives, he wants to be prepared, he says: “If it can be procured, if somebody can pay for it and it can be accessible, it’s game changing.”
j Andrew Green is a journalist based in Berlin.