英國愛滋病協會(BHIVA)表示，最需要注射型HIV藥劑的人是那些無法獲得藥物的人

資料來源：Gus Cairns/2022 年 12 月 7 日/aidsmap

 

利茲福特。 格斯·凱恩斯攝。

 

上個月在倫敦舉行的英國愛滋病協會秋季會議上獲悉，除非病毒載量未受到抑制的人能夠接受注射型抗反轉錄病毒療法 (ART)，否則注射型抗反轉錄病毒療法 (ART) 永遠無法發揮其潛力。

來自國家 HIV 護士協會 (NHIVNA) 的三位主持人在會議上表示，可注射型卡博特韋和利匹韋林(injectable cabotegravir and rilpivirine) 的標準非常嚴格，很少有患者符合條件。

NHS Lothian 的高級主管護士 Linda Panton 說，雖然蘇格蘭的資格標準包括「儘管無法檢測到病毒載量但仍具有令人擔憂的依從性模式」的人和「描述如果繼續口服 ART 有停止治療真正風險的人」，他們目前不能為那些由於難以堅持而實際上確實具有可檢測的病毒載量的人開處方。

NHIVNA 主席 Liz Foote 描述了以同情為由為一名年輕患者申請長效注射劑的過程，該患者由於多種心理社會脆弱性而確實具有可檢測的病毒載量和 CD4 計數下降。

注射用 cabotegravir 和 rilpivirine 於 2020 年 12 月在歐洲（作為 Vocabria 和 Rekambys）獲得許可用作抗反轉錄病毒療法 (ART)，並於 2021 年 1 月在美國獲得許可（這兩種藥物使用同一個品牌名稱 Cabenuva）。

自注射式 ART 開始使用以來，它已被證明在一些患者中很受歡迎並且非常有效，但它的引入並不簡單，需要重新配置服務和員工培訓。

琳達·潘頓 (Linda Panton) 在會議上說，到目前為止，在蘇格蘭大約 5,000 名接受 ART 治療的患者中，只有 22 名 (0.4%) 開始使用注射型 ART，其中一人已恢復口服治療。 在患者、臨床醫生和志願部門最初感到興奮之後，轉診次數少於諮詢師的預期，患者的興趣也降低了。 在鄧迪，該市 HIV 診所的 351 名患者中有 17 名被確定可能受益於長效注射 ART，但實際上只有四名符合標準，其中兩人拒絕了。

除了要求病毒載量不可檢測（至少在過去六個月內低於 50）和「令人擔憂」的依從性水平外，患者還必須「對口服抗反轉錄病毒療法存在心理或生理障礙」。

研究顯示，患者尋求可注射 ART 的動機有很多，包括：擔心身邊有藥丸會導致信息洩露、對保持依從性感到焦慮、不喜歡每天被提醒有 HIV 以及吞嚥藥丸的生理或心理困難。

注射劑也對衛生服務提出了新的要求：預約、病毒載量測試和照護時間（包括用於跟進錯過的預約的時間）加倍；與醫院藥房協調需要冷藏的物資；以及讓患者在接受注射後坐下的空間（建議他們至少等待 30 分鐘）。

開始注射的患者給予好評。 一位說：「不用每天記住吞藥真是太好了」，另一位說：「我現在可以輕鬆過機場海關了」。 然而，一名患者發現很難相信注射劑，擔心它們的效果不會持續整整八週，並意識到對他們來說，每日口服藥丸可以讓他們放心。

大多數患者提到臀部注射部位疼痛，尤其是利匹韋林。這有助於在注射前給予撲熱息痛，並確保注射劑及時從冰箱中取出，使其處於室溫。

患者拒絕注射的主要原因是需要加倍預約。 對於農村地區的患者來說，這尤其是一個問題； 在蘇格蘭，許多人遠道而來，到中心地帶城市接受 HIV 照護。有些人擔心雇主可能會詢問有關額外預約的問題。

為弱勢患者獲取注射劑

無法實現病毒檢測不到的人可能從注射劑中獲益最多，但到目前為止他們還不能，因為關鍵的註冊研究 ATLAS 和 FLAIR 是在接受 ART 檢測不到病毒的患者中進行的。由於依從性、副作用或其他問題而導致治療失敗的患者並不包括在內。

美國國家衛生研究院目前正在招募因 LATITUDE 研究的依從性困難而無法達到檢測不到病毒的人。 然而，即使在這裡，患者也必須堅持口服 ART 方案並使病毒載量低於 200 至少三個月，然後他們才有 50% 的機會去開始注射，儘管降低病毒載量會有經濟上之激勵。

這些要求似乎旨在避免進一步的病毒學失敗和二類耐藥，但臨床醫生似乎對注射療法可能對過去難以堅持的患者的治療成功上可產生重大影響方面有些猶豫。

Liz Foote 在會議上說，即使在英國，超過 91% 的 HIV 感染者被診斷出來並被病毒抑制，只有一小部分患者在依從性和病毒學失敗中掙扎。

在 West Sussex 和 Brighton & Hove 對社區 HIV 照護團隊所支持的患者（因此已經有需求上之支持）所進行的病例數審查發現，45% 的患者「難以堅持」，26% 的患者可檢測到病毒載量。此其中，10% 的人選擇停止服用 ART——「數量雖少但意義重大」。

她描述了一位在社區團隊照顧下的患者。 她在整個童年時期都經歷過創傷，學習困難重重，這意味著她很難堅持自己的 ART； 自診斷以來，她從未達到無法檢測到的病毒載量。她還有多個社會經濟問題，尤其是住房問題。

由於她難以按時到醫院就診，愛滋病毒小組在社區照顧了這位病情複雜的患者，但由於她的依從性問題，她的 CD4 計數開始下降。HIV 團隊越來越擔心她的健康和安全，這不僅是因為 CD4 計數下降，還因為其他社會心理問題。該團隊出於同情心申請在許可條款之外使用長效注射劑。該申請最初因擔心她不參與服務而被拒絕，但在上訴後得到支持。

患者在診所接受了她的第一次卡博特韋和利匹韋林注射，但隨後的注射是由社區 HIV 護士在她家中進行的。 在她第一次注射時，她的病毒載量為 28,000，但在短短兩週內降至 50 以下，並在六週內降至 30 以下。

身邊像她這樣的患者還有很多，但目前打針的人很少。 8 月發表的一項研究發現，截至 7 月，在製造商 ViiV 和楊森 (Janssen) 運營的單一患者同情請求計畫的條件下，10 個國家/地區的 35 名患者開出了 cabotegravir 和 rilpivirine 的處方。這些人當中，在開始時有28 個人具有可檢測的病毒載量（平均 60,000），而有 63% 的人其病毒轉變為無法檢測到。

對於上述患者，「注射改變了她的生活」，利茲富特說。一旦擺脫了應對 HIV 的壓力，她就可以針對其他心理社會需求而努力，尤其是住房。

布萊頓勞森病房診所的喬納森·羅伯茨介紹了一位名叫喬什的患者，他講述了自己今年開始注射藥物的經歷。 他的動機之一是他從事面向公眾的工作，並且擔心客戶會在常規 HIV 診所看到他。 到目前為止，他已經接受了三針注射。 他說他的第一次注射很痛，因為護士將它注射到臀肌更正常的後側，而推薦的注射部位是側面，就在髖骨後面。 他還描述了最初不知道它是否「有效」的焦慮。

然而，長期下來，他感覺身體更健康了：「我不知道是不是心理作用，但我感覺比口服時少了很多疲勞Ｊ。

喬納森·羅伯茨 (Jonathan Roberts) 告訴 aidsmap：「我們正在為第二名有依從性問題的弱勢患者申請超適應症處方外長效注射劑； 他們不會是最後一個」。

 

參考文獻；Foote L、Panton L 和 Roberts J. NHIVNA： 關於可注射 ART 的會議。 BHIVA 秋季會議，皇家內科醫學院，倫敦，2022 年 11 月

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The people who need injectable HIV drugs most are the ones who can’t get them, BHIVA told

Gus Cairns/7 December 2022/aidsmap

 

Liz Foote. Photo by Gus Cairns.

 

Injectable antiretroviral therapy (ART) will never reach its potential until people with unsuppressed viral loads can have it, the British HIV Association’s Autumn Conference heard last month in London.

Three presenters from the National HIV Nurses Association (NHIVNA) told the meeting that the criteria for injectable cabotegravir and rilpivirine were so strict that very few patients are eligible for them.

Linda Panton, a Senior Charge Nurse for NHS Lothian, said that while Scottish eligibility criteria included people with “a concerning adherence pattern despite undetectable viral load” and “people who describe a real risk of stopping treatment if they continue on oral ART”, they could not at present be prescribed for people who due to struggles with adherence actually did have a detectable viral load.

And NHIVNA Chair Liz Foote described the process of applying for long-acting injectables on compassionate grounds for a young patient who did have a detectable viral load and declining CD4 count, due to multiple psychosocial vulnerabilities.

Injectable cabotegravir and rilpivirine were licensed for use as ART in Europe in December 2020 (as Vocabria and Rekambys) and in the US in January 2021 (where the two drugs go under a single brand name, Cabenuva).

Since injectable ART started to be used, it has proved popular with some patients and highly effective, but its introduction has not been simple, requiring reconfiguration of services and staff training.

Linda Panton told the conference that so far just 22 patients out of roughly 5000 on ART in Scotland (0.4%) have started injectable ART, one of whom has gone back to oral therapy. After initial excitement from patients, clinicians and the voluntary sector, there have been fewer referrals than expected from consultants and less interest from patients. In Dundee, 17 out of 351 patients at the city’s HIV clinic were identified as potentially benefitting from long-acting injectable ART but only four actually fitted the criteria and of those, two declined it.

As well as the requirement to have an undetectable viral load (under 50 for at least the last six months) and “concerning” levels of adherence, patients have to have “a psychological or physical barrier to oral antiretroviral therapy”.

Studies have shown that patients have many motivations for seeking injectable ART, including: fear that having pills around will lead to disclosure, anxiety about maintaining adherence, disliking the daily reminder of HIV, and physical or psychological difficulty in swallowing pills.

Injectables also pose new demands on the health service: doubling of appointments, of viral load tests and of nursing time (including time devoted to following up missed appointments); co-ordination of supplies that need cold storage with the hospital pharmacy; and space for the patients to sit after receiving an injection (it’s suggested they wait at least 30 minutes).

Patients who have started the injections comment favourably. One said, “It’s so nice not to have to remember to swallow tablets every day” and another said, “I’m able to relax going through airport customs now”. However, one patient found it difficult to trust the injections, worrying that their effect would not last for the full eight weeks and realising that for them, a daily oral pill offered reassurance.

Most patients mentioned injection site pain in the hip, especially from the rilpivirine. This was helped by giving paracetamol before the injection and making sure the injections were taken out of the fridge in time to be at room temperature.

The main reason patients declined the injectables was due to the doubling of appointments needed. This is especially an issue for patients in rural areas; in Scotland many people travel from afar to receive their HIV care in the central belt cities. Some were worried that employers might ask questions about extra appointments.

Getting injectables for a vulnerable patient

It is people who cannot achieve viral undetectability who might most benefit from the injectables, but so far they can’t, because the crucial registration studies, ATLAS and FLAIR, were conducted in patients virally undetectable on ART. Patients whose therapy was failing due to adherence, side effects or other issues were not included.

The US National Institutes of Health is currently recruiting people who are not virally undetectable due to adherence difficulties for the LATITUDE study. Even here, however, patients will have to stick to an oral ART regime and achieve a viral load under 200 for at least three months before they can even have a 50% chance of starting the injectables, though there will be financial incentives for lowering viral load.

These requirements appear to be aimed at avoiding further viral failure and two-class resistance, but there seems to be some hesitancy among clinicians to believe that injectable therapy might make all the difference to treatment success among patients who have struggled with adherence in the past.

Liz Foote told the conference that even in the UK, with over 91% of people with HIV diagnosed and virally suppressed, there was only a small group of patients who struggled with adherence and virological failure.

A caseload audit in West Sussex and Brighton & Hove among patients supported by the community HIV nursing team (and therefore already with support needs) found that 45% “struggled with adherence” and 26% had a detectable viral load. Of these, 10% had chosen to stop taking ART – “a small but significant number.”

She described one such patient who was under the care of the community team. She had experienced trauma throughout childhood and suffered with a significant learning difficulty which meant that she struggled to adhere to her ART; she had never achieved an undetectable viral load since diagnosis. She also had multiple socio-economic problems, especially with housing.

Because of her difficulty in keeping hospital appointments, the HIV team cared for this complex patient in the community, but due to her adherence issues her CD4 counts started to decline. The HIV team became increasingly worried about her wellbeing and safety, not just due to the CD4 count decline but also other psychosocial issues. The team applied for the use of long-acting injectables outside the terms of their licence, on compassionate grounds. This application was at first refused due to concerns about her lack of engagement with services, but was upheld on appeal.

The patient received her first cabotegravir and rilpivirine injections in the clinic, but subsequent injections were given in her home by community HIV nurses. At the time she had her first injection her viral load was 28,000, but this declined to below 50 in just two weeks and was below 30 within six weeks.

There are many more patients like her around, but currently very few who get the injectables. A study published in August found that up to July there had been 35 patients prescribed cabotegravir and rilpivirine in ten countries under the conditions of the single-patient compassionate request programme operated by the manufacturers ViiV and Janssen. Of these, 28 had a detectable viral load (average 60,000) when they started and 63% became virally undetectable.

As for the above patient, “the injections have transformed her life”, Liz Foote said. Once the pressure of trying to deal with her HIV was taken off, she was able to work on her other psychosocial needs, especially her housing.

Jonathan Roberts from Brighton’s Lawson Unit clinic introduced a patient, Josh, who recounted his own experience of starting injectables this year. One of his motives was that he works in a public-facing job and was worried about customers seeing him in the regular HIV clinic. So far, he has received three injections. He said that his first was painful because the nurse injected it into the more normal posterior side of the gluteal muscle whereas the recommended site is to the side, just behind the hip bone. He also described initial anxiety about not knowing if it was “working”.

However, over the long-term he has felt in better physical health: “I don’t know if it’s psychological or not, but I feel much less fatigue than I did on the orals”.

Jonathan Roberts told aidsmap: “We are in the process of applying for off-label long-acting injectables for a second vulnerable patient with adherence problems; they won’t be the last.”

References

Foote L, Panton L and Roberts J. NHIVNA session on injectable ART. BHIVA Autumn Conference, Royal College of Physicians, London, November 2022.