南非將於 2023 年初開始試行可注射之 PrEP
勞拉·洛佩斯·岡薩雷斯 / 2022 年 11 月 7 日
Hryshchyshen Serhii/Shutterstock.com 網站
健康籌資機制 Unitaid 告訴 aidsmap，南非預計將於 2023 年開始試行可注射暴露前預防 (PrEP)。 示範研究將是眾多希望解決在那裡及以後推出的最大挑戰的眾多研究中的第一個：如何將令人驚訝的複雜注射從診所和醫院轉移到社區。
作為 Unitaid 支持的示範計畫的一部分，南非的少女和年輕女性將率先使用每隔一個月使用抗反轉錄病毒藥物 cabotegravir 的可注射 PrEP。 該試點將遵循該藥物的監管批准，Unitaid 預計將在 2023 年初獲得批准。
辛巴威最近成為第一個批准長效卡博特韋作為 PrEP 的非洲國家。 只有另外兩個國家——美國和澳大利亞——批准了它，但就在幾天前，歐洲藥品管理局證實它已正式接受製藥商 ViiV Healthcare 在歐盟的最終批准申請。
Unitaid 證實，dapivirine 陰道環（也是 PrEP 的一種形式）的類似示範計畫預計將於本月開始。 兩個試點項目都將由 Wits 生殖健康和 HIV 研究所 (Wits RHI) 負責。
Wits RHI 的 HIV 預防注射試驗將是南非國家衛生部設想的幾項實施研究中的第一項，這些研究將為全國推廣提供信息，該部門的 Hasina Subedar 在 7 月舉行的第 24 屆國際愛滋病大會上表示。
「我們從口服 PrEP 中學到的是…… [研究] 在一個非常受控的環境中學習，它不一定反映我們公共衛生機構的真實情況」，她說。「所有這些計畫都需要集中協調，以便他們回答有助於我們做出有關擴大產品規模的決定的問題」。
該國 550 萬接受愛滋病毒治療的人中，絕大多數人透過公共部門獲得抗反轉錄病毒藥物。 PrEP 供應同樣集中。
護士已經接受過培訓，可以提供可能提供可注射 PrEP 的治療
HIV 預防倡導組織 AVAC 整理的數據顯示，到 2020 年，南非約佔全球接受口服 PrEP 的十分之一。 該國與肯亞和美國一起約佔全球口服 PrEP 人口的 40%。
Subedar 解釋說，國家推廣的許多細節將部分取決於國家監管機構南非健康產品監管局 (SAHPRA) 如何對 HIV 預防注射進行分類。 例如，監管機構施加的限制（稱為時間表）將決定誰可以對其進行管理。 SAHPRA 還可以根據可用數據選擇限制某些群體的注射。
該國的專家們已經在考慮由誰、在哪裡以及如何推出——前提是每隔一個月的注射變得負擔得起。 大多數專家都同意，需要經過專門培訓的護士進行注射。 難以管理的可注射卡博特拉韋將如何進入社區並更接近患者尚不清楚。 移動醫療服務甚至新的社區「注射診所」都可能是分散模式的一部分，這些模式將提供注射以及其他性健康和生殖健康服務。 最後，醫護人員將不得不弄清楚如何就幾乎全新的事物向人們提供諮詢：預防愛滋病毒的真正選擇。
「活動家希望我們昨天在街角分發東西——在蒙特利爾國際愛滋病大會上肯定有這種感覺」，研究機構 Ezintsha 的部門主任 Francois Venter 博士在最近的南部非洲在約翰內斯堡 HIV 臨床醫生協會會議上說。「在我們這樣做之前需要進行一些盤點」。
「但我們的患者將推動我們走得非常快」，他繼續說道。「我們有一些時間來弄清楚[可注射的 PrEP]，但我們不能坐以待斃多年」。
大問題：在哪裡提供注射劑
Saiqa Mullick 博士是 Wits RHI 的實施科學總監，該機構是南非首批與國家衛生部門合作提供口服 PrEP 的組織之一。 最初是從性工作者開始推出，然後是年輕女性，最後是她們的伴侶。
「我們吸取的一個教訓是，儘管我們非常關注青春期女孩和年輕女性的 PrEP，但我們開始看到男性前來尋求預防服務」，她說。
Mullick 認為，至少在最初階段，提供可注射 PrEP 的工作將由一小部分護士負責，這些護士已經接受過在南非提供 HIV 治療和口服 PrEP 的培訓。 然而，即使是這些護士也需要額外的培訓。
但在社區中確定提供 HIV 預防注射的地點將更加棘手。
「這是我們需要快速回答的最大的實施科學問題之一」， Linda-Gail Bekker 教授說。 Bekker 是 Desmond Tutu 健康基金會的首席運營官，也是國際愛滋病協會的前任主席。「藥丸使差異化服務的提供變得非常容易：你可以透過快遞寄藥……給人們幾個月的配藥……我不能用長效卡博特韋做到這一點」。
差異化的服務交付模式通常包括將服務移出設施、減少門診就診或轉移服務任務以使患者的照護更輕鬆、更好。
Bekker 認為，社區「注射診所」可能會成為未來可注射 PrEP 服務的一部分——與傳統醫院、診所和移動外展服務並駕齊驅。
「難以管理的可注射卡博特韋將如何進入社區尚不清楚」。
經常評判年輕人尋求性健康和生殖健康服務的年長社區成員的窺探眼光。
「你會發現我們讓一個年輕女孩接受 PrEP，然後這個女孩會回來說她的父母扔掉了 PrEP，因為他們認為……她太小不能發生性行為」， Kwatsha 解釋道。 Wits RHI 現在定期舉辦社區活動，包括在教堂舉辦的活動，不僅針對年輕女性和其他重點人群，還針對她們的朋友和家人。「透過讓他們的父母參與進來，我們確保讓整個社區了解年輕人如何以不危及他們未來的方式進行安全性行為」。
一些服務也在路上採用口服 PrEP，通過移動診所提供，Mullick 說她認為這可能是注射 PrEP 交付的一種選擇。
儘管如此，Mullick 說，協調移動 PrEP 診所可能具有挑戰性，並且需要一個複雜的追踪系統來確保移動診所就診與患者的用藥時間表保持一致。
Paul Botha 是 Engage Men 的網站協調員，該公司為約翰尼斯堡的男同性戀者、雙性戀者和其他男男性行為者提供 PrEP。 Engage Men 通過招募社區大使在家庭或酒吧為 gbMSM 社區舉辦信息會議來部分做到這一點。 Botha 承認，Engage Men 的流動診所一直在努力跟上不斷增長的需求並應對未出現的情況。
「就我們的消息傳遞而言，我們必須確保人們知道我們將向他們交付一次」，他說。「如果他們不在那裡，他們就會放棄 [送貨] 服務」。
為什麼可能是時候改變世界衡量 PrEP 使用的方式了
Kwatsha 在 Wits RHI 的部分工作是給錯過約會的病人打電話，對一些人來說，「沒有出現」是他們不再覺得有感染 HIV 風險的標誌。 他們可能沒有發生性行為，或者關係狀況發生了變化。 當他們對風險的看法發生變化時，他們可能會再次打電話給她以重新啟動 PrEP。
Mullick 說，在公共衛生系統內很難追踪關於循環使用和停止口服 PrEP 的人的數據，但一直在增長。
「當你處於危險季節時，你應該服用 PrEP。這不是 HIV 治療——你不必終生服用」，她解釋說。「當你不在時危險季節時，你可以停止服用」。「冒險回來重新開始」。
穆利克繼續說道：「這個信息肯定會傳來……因為重啟正在增加」。
直到現在，PrEP計畫目——在許多國家無法隨著時間的推移追踪患者——已經透過有多少人開始服用避孕藥來衡量成功。 很少有人能夠確切地說出在任何給定時間有多少人在服用 PrEP。
在 Unitaid 資助下，Wits RHI 將尋求更好地了解和追踪人們如何循環使用口服和注射 PrEP 以及陰道環。
「該領域現在正在考慮如何以更有意義的方式衡量 PrEP 的使用」，Mullick 補充道。
選擇將是提高吸收率的關鍵
然而，Mullick、Bekker 和 Botha 都同意，無論醫護人員如何將 HIV 預防注射引入社區，它至少必須與一攬子性健康和生殖健康服務一起提供。
同時，有關 HIV 預防注射的信息必須在社區中切中要害。
醫護人員將不得不弄清楚如何就一些新穎的東西向人們提供建議：］預防愛滋病毒的真正選擇」。
「該領域已經學到了很多關於如何傳遞 PrEP 信息，並將其定位為具有增強信息傳遞能力的健康產品」， Mullick 解釋說。「我們已經提出，你有能力將自己的健康和福祉掌握在自己手中——這是我們學到的最重要的事情」。
近四十年來，一個人的 HIV 預防選擇主要局限於保險套。 現在，隨著可注射 PrEP 和 dapivirine 環的推出，醫護人員將不得不改變他們的思維方式——並與患者和社區討論預防選擇。
她補充說：「我們的提供者從未需要圍繞生物醫學選項的選擇進行諮詢」。「選擇方面非常重要，因為我們從計畫生育計畫中學到的是，您擁有的選擇越多，您獲得的覆蓋面和影響就越大」。
更正：本文於2022年11月7日修改。之前的版本說cabotegravir需要冷藏。
South Africa to begin piloting injectable PrEP in early 2023
Laura López González / 7 November 2022
Hryshchyshen Serhii/Shutterstock.com
South Africa is expected to begin piloting injectable pre-exposure prophylaxis (PrEP) in 2023, health financing mechanism Unitaid tells aidsmap. The demonstration study will be the first of many hoping to answer the single biggest challenge for a rollout there and beyond: How to take a surprisingly complicated injection out of clinics and hospitals and into communities.
Adolescent girls and young women in South Africa will be the first to access injectable PrEP using the antiretroviral drug cabotegravir every other month as part of the Unitaid-supported demonstration project. The pilot will follow regulatory approval for the drug, which Unitaid expects in early 2023.
Zimbabwe recently became the first African country to approve long-acting cabotegravir as PrEP. Only two other countries – the United States and Australia – have approved it, but just days ago, the European Medicines Agency confirmed it had formally accepted drugmaker ViiV Healthcare’s application for eventual approval in the European Union.
A similar demonstration project for the dapivirine vaginal ring — also a form of PrEP — is expected to begin this month, Unitaid confirmed. Both pilots will be run by the Wits Reproductive Health and HIV Institute (Wits RHI).
Wits RHI’s pilot of the HIV prevention injection will be the first of several implementation studies envisioned by the South African National Health Department that will inform a national rollout, the department’s Hasina Subedar said at the 24th International AIDS Conference in July.
“What we learned from oral PrEP is that… [studies] learn in a very controlled environment and it doesn’t necessarily reflect the real-world situation in our public health facilities,” she said. “There needs to be central coordination of all these projects so that they answer the questions that will assist us in making a decision about scale-up of the product.”
The vast majority of the country’s 5.5 million people on HIV treatment receive their antiretrovirals through the public sector. PrEP provision remains similarly concentrated.
Nurses already trained to provide treatment likely to provide injectable PrEP
South Africa accounted for about one in 10 people on oral PrEP globally in 2020, data collated by the HIV prevention advocacy organisation AVAC shows. The country — together with Kenya and the United States — made up about 40% of people on oral PrEP globally.
Many of the details of a national rollout will be in part decided by how the national regulator, the South African Health Products Regulatory Authority (SAHPRA), classifies the HIV prevention injection, Subedar explained. Restrictions imposed by the regulator (known as schedules) will determine who can administer it, for example. SAHPRA could also choose to limit the injection for certain groups, depending on available data.
Experts in the country are already thinking about the who, where and how of the rollout — provided the every-other month injection becomes affordable. Specially trained nurses will need to provide the injection, most experts agree. Just how injectable cabotegravir, which is difficult to administer, will be taken into communities and closer to patients is less clear. Mobile health services and even new, community ‘shot clinics’ may all be part of decentralised models that will provide the injection alongside other sexual and reproductive health services. Finally, healthcare workers will have to figure out how to counsel people on something almost completely novel: Real choice in HIV prevention.
“Activists want us handing stuff out on street corners yesterday — that certainly was the feeling at the International AIDS Conference in Montreal,” Dr Francois Venter, divisional director of the research institute Ezintsha, said at a recent meeting of the Southern African HIV Clinicians Society in Johannesburg. “There needs to be a bit of a stock taking before we do that.”
“But our patients are going to be pushing us to go very fast,“ he continued. “We’ve got some time to figure [injectable PrEP] out but we can’t sit on our hands wondering about it for years.”
The big question: Where to provide the injections
Dr Saiqa Mullick is director of implementation science at Wits RHI, which was one of the first organisations in South Africa to partner with the national health department to provide oral PrEP. The rollout began initially with sex workers and then later to young women and, eventually, their partners.
“One lesson that we have learnt was that even though we focused very much on PrEP for adolescent girls and young women, we started seeing men coming in for prevention services,” she said.
Mullick believes that, at least initially, providing injectable PrEP will fall to a relatively small cadre of nurses already trained to provide HIV treatment and oral PrEP in South Africa. Even these nurses however will need additional training.
But working out locations in communities from which to provide the HIV prevention injection will be more tricky.
“That is one of the biggest implementation science questions that we need to answer quickly,” said Professor Linda-Gail Bekker. Bekker is the chief operating officer of the Desmond Tutu Health Foundation and a past president of the International AIDS Society. “Pills made differentiated service delivery so incredibly easy: You can send pills by courier…give people multi-month dispensing…I can’t do that with long-acting cabotegravir.”
Differentiated service delivery models typically include moving services out of facilities, reducing clinic visits or task-shifting services to make care easier and better for patients.
Bekker believes that community ‘shot clinics’ might be part of how injectable PrEP services look in the future — alongside traditional hospitals, clinics and mobile outreach services.
“Just how injectable cabotegravir, which is difficult to administer, will be taken into communities is unclear.”
“You need a nurse who is specially trained to give an injection, which needs privacy — be it only every two months. Still, for that, you need infrastructure,” she says. “We are going to look and see if we can do a shot clinic: A trailer with the nurse and the counsellor, so if I’m just needing my maintenance shot, I literally go and get my shot and leave.”
Both the Desmond Tutu Health Foundation and Wits RHI have also invested heavily in offering oral PrEP via specially-created youth-friendly spaces, including at public clinics.
These options allow young people to skip the usual clinic queue, explains Wits RHI linkage to care officer Khanyi Kwatsha — and the prying eyes of older community members who often judge young people for seeking out sexual and reproductive health services.
“You will find that we initiate a young girl on PrEP and then the girl will come back to say that her parents threw away the PrEP because they thought… she was too young to have sex,” Kwatsha explained. Wits RHI now holds regular community events, including at churches, aimed not just at young women and other key populations, but also at their friends and family. “By involving their parents, we are making sure we sensitise the whole community on how youth can have safe sex in a way whereby they don’t jeopardise their future.”
Several services have also taken oral PrEP on the road, offering it via mobile clinics that Mullick said she believes could be an option for injectable PrEP delivery.
Still, coordinating mobile PrEP clinics can be challenging, and requires a complicated tracking system to ensure that mobile clinic visits align with patients’ medication schedules, Mullick says.
Paul Botha is a site coordinator for Engage Men, which offers PrEP to gay, bisexual and other men who have sex with men in Johannesburg. Engage Men does this in part by recruiting community ambassadors who hold information sessions for the gbMSM community at homes or bars. Botha admitted that Engage Men’s mobile clinics have struggled to keep pace with rising demand and to deal with no-shows.
“In terms of our messaging, we have to make sure that people know we’re going to deliver to them once,” he said. “If they’re not there, they forfeit the [delivery] service.”
Why it might be time to change how the world measures PrEP use
Part of Kwatsha’s job at Wits RHI is to call patients who have missed appointments and for some, a ‘no-show’ is a sign that they no longer feel at risk of HIV. They may not be having sex, or had a change in relationship status. When their perception of risk changes, they may call her back again to restart PrEP.
Mullick says data on people who have cycled on and off oral PrEP has been difficult to track within the public health system but has been growing.
“You should be on PrEP when you’re in a season of risk. It’s not HIV treatment — you don’t have to be on it for a lifetime,” she explains. “You can be off it when you’re not at risk and come back to reinitiate.”
Mullick continued: “That message is definitely coming through… because restarts are going up.”
Until now, PrEP programmes — unable to track patients over time in many countries — have measured success by how many people had ever started taking the pill. Few are able to say definitively how many people are on PrEP at any given time.
Under the Unitaid grant, Wits RHI will be looking to better understand — and track — how people cycle on and off oral and injectable PrEP as well as the vaginal ring.
“The field is now thinking about how to measure PrEP use in a more meaningful way,” Mullick added.
Choice will be key to increasing uptake
Mullick, Bekker and Botha all agree however that regardless of how healthcare workers take the HIV prevention injection into communities, it will have to be provided at least alongside a wraparound package of sexual and reproductive health services.
Meanwhile, messages around the HIV prevention injection will have to hit the mark with communities.
Healthcare workers will have to figure out how to counsel people on something novel: Real choice in HIV prevention.”
“The field has learned a lot more about how to message PrEP and positioning it as a wellness product with empowering messaging,” Mullick explains. “We have put forward that you have the power to take into your hands your health and wellbeing — that’s the big thing we learned.”
For almost four decades, a person’s HIV prevention options were largely confined to the condom. Now, with injectable PrEP and the dapivirine ring in the pipeline, healthcare workers will have to change the way they think — and talk about prevention choice to patients and communities.
“Our providers have never had to counsel around the choice of biomedical options,” she added. “The choice aspect is really important because what we’ve learned from family planning programmes is that the more choices you have, the more coverage and impact you’re going to get.”
Correction: This article was amended on 7 November 2022. The previous version stated that cabotegravir requires refrigeration.