對於沒有病毒抑制的人來說，長效卡博特拉韋(cabotegravir)和利匹韋林(rilpivirine)可能是可行的

資料來源：Liz Highleyman / 2022 年 8 月 23 日 /aidsmap/ 則財團法人台灣紅絲帶基金會編譯

圖片：卡蘭·邦讓/Shutterstock.com

根據在第 24 屆國際愛滋病會議 (AIDS 2022) 上發表並發表在《臨床傳染病》上的一項研究，對於因治療依從性不佳而無法實現病毒抑制的 HIV 感染者，長效卡博特拉韋和利匹韋林注射液可能是一種選擇.

ViiV Healthcare 的新型整合酶抑製劑可注射 cabotegravir (Vocabria) 與楊森 (Janssen) 的 NNRTI rilpivirine (Rekambys) 是第一個不需要每日服藥的完整抗反轉錄病毒療法。在美國和加拿大，這兩種藥物一起作為 Cabenuva 銷售。該治療包括由醫療保健提供者每月或每隔一個月在臀部進行兩次肌肉注射。

如先前報導的，兩項 III 期臨床試驗顯示，卡博特韋和利匹韋林的雙重注射導致持續的病毒抑制。 ATLAS 研究評估了該方案作為在標準口服方案中病毒載量穩定且無法檢測到的接受過治療的人的維持治療。 FLAIR 研究招募了以前未經治療的人，但他們開始採用口服方案，並在改用注射之前實現了病毒抑制。

歐洲藥品管理局和美國食品藥品監督管理局 (FDA) 均已批准注射 cabotegravir 和 rilpivirine 僅用於 HIV 目前通過穩定的抗反轉錄病毒療法得到控制且對這兩種藥物沒有耐藥性的人。 FDA 進一步排除了那些有治療失敗史的人。

儘管注射劑經常被描述為對被發現依從性具有挑戰性的人身上具有優勢，但病毒已經被抑制的要求限制了 cabotegravir 和 rilpivirine 的使用。

美國加利福尼亞大學舊金山分校的 Katerina Christopoulos 博士及其同事進行了一項初步研究，以評估注射型 cabotegravir 和 rilpivirine 是否可以成為因堅持口服抗反轉錄病毒治療的挑戰而無法實現或維持病毒受抑制者的另一種選擇。

「對於沒有達到病毒抑制且無法獲得如此密集支持的人來說，注射療法可能不是一種選擇」。

可注射的cabotegravir 和rilpivirine 是安全的並且通常耐受性良好。注射部位反應大多為輕度至中度，但有一名患者在注射部位出現蜂窩組織炎。惟並沒有人由於副作用決定停止注射療法。

研究作者總結說：「這個小型的長效注射抗反轉錄病毒治療示範計畫在物質濫用層度高且居住條件差的不同患者群體中展示了具有希望的早期治療結果，且包括那些因依從性挑戰而可檢測到病毒血症的患者」。

他們指出，五名參與者正在接受其他長效注射（精神科藥物或納曲酮來控製酒精或阿片類藥物使用障礙），強調了利用其他注射就診來提供長效 HIV 治療的承諾。

研究人員承認，對於沒有病毒抑制、無法獲得如此密集支持的人來說，注射療法可能不是一種選擇。這種方法超出了歐盟 EMA 和美國 FDA 對長效 cabotegravir 和 rilpivirine 的適應症，並且需要謹慎，因為不一致的使用可能導致非核苷類反轉錄酶抑制劑 (NNRTI) 和整合酶抑製劑的雙重耐藥，從而限制了其他治療之選擇。

舊金山提供出色的愛滋病毒照護，該市為無家可歸者提供廣泛的服務。更重要的是，該計畫能夠克服美國醫療保健系統的一些弊端。與美國許多其他州不同，加利福尼亞州通過其 Medicaid 計畫和 AIDS 藥物援助計畫涵蓋 cabotegravir 和 rilpivirine。

「86 號病房是一個特殊的地方，幾乎不能代表大多數 HIV、ID [傳染病] 或初級的保健診所」，波士頓布萊根婦女醫院的 Paul Sax 博士在一篇關於這項研究的博客文章中寫道。 「他們擁有大量專門的現場資源來加強對難接觸到的患者群體之照護。這包括醫生、護士、藥劑師、社會工作者——一支名副其實的大軍，可以支持和追捕那些在接受愛滋病毒治療時可能誤入歧途的人……我們之中有多少的愛滋病毒提供者可以獲得這種全方位的照護？換句話說，如果你在進行標準的 [傳染病] ID 或 HIV 臨床實踐，暫時不要在家裡嘗試這個」。

「到目前為止，我們對不接受口服 ART [抗反轉錄病毒療法] 的人的選擇非常有限」，他繼續說道。 「嘗試採用這種替代方法可能就是與愛滋病毒相關的死亡。在2022 年不應有人會因我們不能盡一切可能讓他們接受抗反轉錄病毒治療而死於愛滋病。甚至如果這裡亦包括了未經批准而使用 cabotegravir 和 rilpivirine」。

參考文獻：

Christopoulos KA等人。在城市的 HIV 診所中為即可檢測到和未能檢測到 HIV 病毒血症的人進行長效注射型抗反轉錄病毒治療的第一個示範計畫。臨床傳染病，在線提前印刷，2022 年 8 月 1 日（開放獲取）。https://doi.org/10.1093/cid/ciac631

Christopoulos KA等人。在安全網中的 HIV 診所，長效可注射型 cabotegravir 和 rilpivirine 的早期實施和臨床結果。第 24 屆國際愛滋病大會，蒙特婁，摘要 EPB186，2022。

Long-acting cabotegravir and rilpivirine may be feasible for people without viral suppression

Liz Highleyman / 23 August 2022 /aidsmap

Karan Bunjean/Shutterstock.com

Long-acting cabotegravir and rilpivirine injections may be an option for people with HIV who have been unable to achieve viral suppression due to suboptimal treatment adherence, according to a study presented at the 24th International AIDS Conference (AIDS 2022) and published in Clinical Infectious Diseases.

Injectable cabotegravir (Vocabria), a new integrase inhibitor from ViiV Healthcare, plus Janssen’s NNRTI rilpivirine (Rekambys) is the first complete antiretroviral regimen that does not require daily pills. In the United States and Canada, the two drugs are marketed together as Cabenuva. The treatment involves two intramuscular injections in the buttocks administered by a healthcare provider once monthly or every other month.

As previously reported, two phase III clinical trials showed that dual injections of cabotegravir and rilpivirine led to sustained viral suppression. The ATLAS study evaluated the regimen as maintenance therapy for treatment-experienced people who had a stable undetectable viral load on a standard oral regimen. The FLAIR study enrolled previously untreated people, but they were started on an oral regimen and achieved viral suppression before switching to the injections.

Both the European Medicines Agency and the US Food and Drug Administration (FDA) have approved injectable cabotegravir and rilpivirine only for people whose HIV is currently under control on a stable antiretroviral regimen and who have no resistance to the two drugs. The FDA further excludes those with a prior history of treatment failure.

While injectables have often been described as having advantages for people who find adherence challenging, the requirement to already be virally suppressed has limited the uptake of cabotegravir and rilpivirine.

Dr Katerina Christopoulos of the University of California at San Francisco and colleagues conducted a pilot study to assess whether injectable cabotegravir and rilpivirine could be an option for people who are unable to achieve or maintain viral suppression due to challenges adhering to oral antiretroviral therapy.

“The injectable regimen might not be an option for people without viral suppression who do not have access to such intensive support.”

Injectable cabotegravir and rilpivirine was safe and generally well tolerated. Injection site reactions were mostly mild to moderate, but one person developed cellulitis at the injection site. No one decided to stop the injectable regimen due to side effects.

“This small demonstration project of long-acting injectable antiretroviral therapy in a diverse group of patients with high levels of substance use and marginal housing demonstrated promising early treatment outcomes, including in those with detectable viremia due to adherence challenges,” the study authors concluded.

They noted that five participants were receiving other long-acting injections (psychiatric medications or naltrexone to manage alcohol or opioid use disorders), highlighting the promise of leveraging attendance at other injection visits to deliver long-acting HIV treatment.

The researchers acknowledged that the injectable regimen might not be an option for people without viral suppression who do not have access to such intensive support. This approach goes beyond the EMA and FDA indications for long-acting cabotegravir and rilpivirine, and it warrants caution as inconsistent use could lead to dual NNRTI and integrase inhibitor resistance that limits other treatment options.

San Francisco offers excellent HIV care, and the city provides extensive services for people experiencing homelessness. What’s more, this programme was able to overcome some of the drawbacks of the American health care system. Unlike many other US states, California covers cabotegravir and rilpivirine through its Medicaid programme and its AIDS Drug Assistance Program.

“Ward 86 is a special place, hardly representative of most HIV, ID [infectious disease] or primary care clinics,” Dr Paul Sax of Brigham and Women’s Hospital in Boston wrote in a blog post about the study. “They have tons of dedicated on-site resources to enhance the care of their difficult-to-reach patient population. This includes doctors, nurses, pharmacists, social workers—a veritable army of people available to support and chase down people who might go astray while on HIV therapy….How many of us HIV providers have access to this kind of wraparound care? In other words, if you’re in a standard ID or HIV clinical practice, don’t try this at home quite yet.”

“Up to this point, our options for people who won’t take oral ART [antiretroviral therapy] have been highly limited,” he continued. “The alternative to trying this might be an HIV-related death. And no one in 2022 should die of AIDS without our doing everything we possibly can to get them on antiretroviral therapy. Even if that includes an unapproved use of cabotegravir and rilpivirine.”

References

Christopoulos KA et al. First demonstration project of long-acting injectable antiretroviral therapy for persons with and without detectable HIV viremia in an urban HIV clinic. Clinical Infectious Diseases, online ahead of print, 1 August2022 (open access).

https://doi.org/10.1093/cid/ciac631

Christopoulos KA et al. Early implementation and clinical outcomes of long-acting injectable cabotegravir and rilpivirine in a safety-net HIV clinic. 24th International AIDS Conference, Montreal, abstract EPB186, 2022.